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Hwang, Eun-Sil Shelley

Positions:

Mary and Deryl Hart Professor of Surgery, in the School of Medicine

Surgical Oncology
School of Medicine

Professor of Surgery

Surgical Oncology
School of Medicine

Vice Chair of Research in the Department of Surgery

Surgery
School of Medicine

Professor of Radiology

Radiology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1991

M.D. — University of California at Los Angeles

M.P.H. 2006

M.P.H. — University of California at Berkeley

Intern, General Surgery

Kaiser Foundation Hospital

Resident, General Surgery

Cornell University

Fellow, Breast Surgical Oncology

Memorial Sloan Kettering Cancer Center

Senior Reigstrar, General Surgical Oncology

Singapore General Hospital

Assistant Professor in Residence, Surgery

University of California, San Francisco, School of Medicine

Associate Professor in Residence, Surgery

University of California, San Francisco, School of Medicine

Chief, Division Of Breast Surgery Oncology

University of California, San Francisco, School of Medicine

Professor in Residence, Surgery

University of California, San Francisco, School of Medicine

Surgeon-in-Chief, Ucsf Helen Diller Family Cancer Center

University of California, San Francisco, School of Medicine

News:

Dr. Shelley Hwang: New measure of mastectomy

March 22, 2016 — The New York Times

Study: Chemo unnecessary in many cases of early-stage breast cancer

October 05, 2015 — NPR’s “Here & Now”

Think pink: Lumpectomy vs. mastectomy

October 04, 2013 — Ivanhoe Newswire

Grants:

NCI National Clinical Trials Network (UG1)

Administered By
Duke Cancer Institute
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
March 06, 2019
End Date
February 25, 2025

Breast Pre-Cancer Atlas Center

Administered By
Surgical Oncology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 21, 2018
End Date
June 30, 2023

Duke CTSA (KL2)

Administered By
Institutes and Centers
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
May 02, 2018
End Date
April 30, 2023

Building Interdisciplinary Research Careers in Women's Health

Administered By
Obstetrics and Gynecology
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
September 26, 2002
End Date
July 31, 2022

Building Interdisciplinary Research Careers in Women's Health

Administered By
Obstetrics and Gynecology
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
September 26, 2002
End Date
July 31, 2022

TBCRC 034 DFCI 15-174

Administered By
Duke Cancer Institute
AwardedBy
Johns Hopkins University
Role
Principal Investigator
Start Date
March 07, 2016
End Date
June 27, 2022

Comparison of Operative to Medical Endocrine Therapy (COMET) for Low Risk DCIS

Administered By
Surgical Oncology
Role
Principal Investigator
Start Date
June 01, 2016
End Date
December 01, 2021

Translational Research in Surgical Oncology

Administered By
Surgery, Surgical Sciences
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
January 01, 2002
End Date
August 31, 2021

Regional Oncolytic Poliovirus Immunotherapy for Breast Cancer

Administered By
Surgery, Surgical Sciences
AwardedBy
Department of Defense
Role
Co Investigator
Start Date
August 01, 2016
End Date
July 31, 2021

Genomic Diversity and the Microenvironment as Drivers of Progression in DCIS

Administered By
Surgical Oncology
AwardedBy
Department of Defense
Role
Principal Investigator
Start Date
September 30, 2014
End Date
September 29, 2020

Characterization of Tumor Immunobiological Factors that Promote Lymphovascular Invasion and Dissemination in Locally Advanced Breast Cancer

Administered By
Surgery, Surgical Sciences
AwardedBy
Department of Defense
Role
Co Investigator
Start Date
August 15, 2017
End Date
August 14, 2020

Preoperative Breast Radiotherapy: A Tool to Provide Individualized and Biologically-Based Radiation Therapy

Administered By
Radiation Oncology
Role
Collaborator
Start Date
July 01, 2015
End Date
May 07, 2020

Prevent Ductal Carcinoma in Situ Invasive Overtreatment Now - PRECISION

Administered By
Surgical Oncology
Role
Principal Investigator
Start Date
May 01, 2017
End Date
April 30, 2020

Tissue tension, RANK and Breast Cancer Risk

Administered By
Surgical Oncology
AwardedBy
University of California, San Francisco
Role
Principal Investigator
Start Date
February 09, 2018
End Date
January 31, 2020

Comparing the Effectiveness of Guideline-concordant Care to Active Surveillance for DCIS: an Observational Study

Administered By
Surgical Oncology
AwardedBy
Patient Centered Outcomes Research Institute
Role
Principal Investigator
Start Date
November 01, 2015
End Date
January 31, 2020

Molecular and Radiologic Predictors of Invasion in a DCIS Active Surveillance Cohort

Administered By
Surgical Oncology
Role
Principal Investigator
Start Date
October 01, 2018
End Date
September 30, 2019

Targeting DAMP-induced inflammation to prevent metastasis

Administered By
Surgery, Surgical Sciences
AwardedBy
Department of Defense
Role
Co Investigator
Start Date
September 30, 2016
End Date
September 29, 2019

CALGB 40903

Administered By
Surgical Oncology
Role
Principal Investigator
Start Date
October 01, 2017
End Date
September 15, 2019

Cancer Prevention Agent Development Program: Early Phase Clinical Research - CR

Administered By
Surgical Oncology
AwardedBy
Northwestern University
Role
Principal Investigator
Start Date
September 15, 2016
End Date
September 14, 2019

(PQC3) Genomic Diversity and Microenvironment as Drivers of Metastasis in DCIS

Administered By
Surgical Oncology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
August 01, 2014
End Date
July 31, 2019

Feasibility study phase C: Expansion into multiple institutions for training in the use of the LUM imaging system for intraoperative detection of residual cancer in the tumor bed of female subjects

Administered By
Surgical Oncology
Role
Principal Investigator
Start Date
October 01, 2017
End Date
June 30, 2019

NCI National Clinical Trials Network U10 (Year 5)

Administered By
Duke Cancer Institute
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
April 14, 2014
End Date
February 28, 2019

Genetic testing for women with high-risk breast lesions

Administered By
Surgical Oncology
Role
Collaborating Investigator
Start Date
November 01, 2017
End Date
October 31, 2018

Molecular and Radiologic Predictors of Invasion in a DCIS Active Surveillance Cohort

Administered By
Surgical Oncology
Role
Principal Investigator
Start Date
October 01, 2016
End Date
September 30, 2018

Cancer Prevention Agent Development Program: Early Phase Clinical Research - FP

Administered By
Surgical Oncology
AwardedBy
Northwestern University
Role
Principal Investigator
Start Date
September 15, 2016
End Date
September 14, 2018

The Mathematics of Breast Cancer Overtreatment: Improving Treatment Choice through Effective Communication of Personalized Cancer Risk

Administered By
Surgical Oncology
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
September 01, 2016
End Date
August 31, 2018

Genomic Health Oncotype DX DCIS Score

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
November 01, 2013
End Date
October 31, 2017

Optimizing Parameters and Techniques in Circulation Tumor Cell Collection (OPTICOLL)

Administered By
Surgical Oncology
AwardedBy
University of Southern California
Role
Principal Investigator
Start Date
April 01, 2015
End Date
March 31, 2017

Optimizing Parameters and Techniques in Circulation Tumor Cell Collection (OPTICOLL)

Administered By
Surgical Oncology
Role
Principal Investigator
Start Date
February 05, 2013
End Date
November 30, 2014
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Publications:

The effect of treatment on patient-reported distress after breast cancer diagnosis.

BACKGROUND: The National Comprehensive Cancer Network (NCCN) Distress Thermometer (DT) uses a 10-point scale (in which 0 indicates no distress and 10 indicates extreme distress) to measure patient-reported distress. In the current study, the authors sought to examine the relationship between treatment and NCCN DT scores in patients with breast cancer over time. METHODS: The authors included women aged ≥18 years who were diagnosed with stage 0 to stage IV breast cancer (according to the seventh edition of the American Joint Commission on Cancer staging system) at a 3-hospital health system from January 2014 to July 2016. Linear mixed effects models adjusted for covariates including stage of disease, race/ethnicity, insurance, and treatment sequence (neoadjuvant vs adjuvant) were used to estimate adjusted mean changes in the DT score (MSCs) per week for patients undergoing lumpectomy, mastectomy only, and mastectomy with reconstruction (MR). RESULTS: The authors analyzed 12,569 encounters for 1029 unique patients (median score, 4; median follow-up, 67 weeks). Patients treated with MR (118 patients) were younger and more likely to be married, white, and privately insured compared with patients undergoing lumpectomy (620 patients) and mastectomy only (291 patients) (all P < .01). After adjusting for covariates, distress scores were found to decline significantly across all 3 surgical cohorts, with patients undergoing MR found to have both the most preoperative distress and the greatest decline in distress prior to surgery (MSC/week: -0.073 for MR vs -0.031 for lumpectomy vs -0.033 for mastectomy only; P = .001). Neoadjuvant therapy was associated with a longitudinal decline in distress for patients treated with lumpectomy (-1.023) and mastectomy only (-0.964). Over time, ductal carcinoma in situ (-0.503) and black race (-1.198) were found to be associated with declining distress among patients treated with lumpectomy and MR, respectively, whereas divorced patients who were treated with mastectomy only (0.948) and single patients treated with lumpectomy (0.476) experienced increased distress (all P < .05). CONCLUSIONS: When examined longitudinally in consecutive patients, the NCCN DT can provide patient-reported data to inform expectations and guide targeted support for patients with breast cancer.

Authors
Fayanju, OM; Yenokyan, K; Ren, Y; Goldstein, BA; Stashko, I; Power, S; Thornton, MJ; Marcom, PK; Hwang, ES
MLA Citation
Fayanju, Oluwadamilola M., et al. “The effect of treatment on patient-reported distress after breast cancer diagnosis..” Cancer, vol. 125, no. 17, Sept. 2019, pp. 3040–49. Pubmed, doi:10.1002/cncr.32174.
PMID
31120575
Source
pubmed
Published In
Cancer
Volume
125
Issue
17
Publish Date
2019
Start Page
3040
End Page
3049
DOI
10.1002/cncr.32174

The Influence of Age on the Histopathology and Prognosis of Atypical Breast Lesions.

BACKGROUND: Although several prognostic variables and risk factors for breast cancer are age-related, the association between age and risk of cancer with breast atypia is controversial. This study aimed to compare the type of breast atypia and risk of underlying or subsequent breast cancer by age. METHODS: Adult women with breast atypia (atypical ductal hyperplasia, atypical lobular hyperplasia, and lobular carcinoma in situ) at a single institution from 2008 to 2017 were stratified by age at initial diagnosis: <50 y, 50-70 y, and >70 y. Regression modeling was used to estimate the association of age with risk of underlying carcinoma or subsequent cancer diagnosis. RESULTS: A total of 530 patients with atypia were identified: 31.1% < 50 y (n = 165), 58.1% 50-70 y (n = 308), and 10.8% > 70 y (n = 57). The proportion of women with atypical ductal hyperplasia steadily increased with age, compared with atypical lobular proliferations (P = 0.04). Of those with atypia on needle biopsy, the overall rate of underlying carcinoma was 17.5%. After adjustment, older age was associated with a greater risk of underlying carcinoma (odds ratio: 1.028, 95% confidence interval: 1.003-1.053; P = 0.03). Of those confirmed to have atypia on surgical excision, the overall rate of a subsequent cancer diagnosis was 15.7%. Age was not associated with a long-term risk for breast cancer (P = 0.48) or the time to a subsequent diagnosis of carcinoma (log-rank P = 0.41). CONCLUSIONS: Although atypia diagnosed on needle biopsy may be sufficient to warrant surgical excision, older women may be at a greater risk for an underlying carcinoma, albeit the long-term risk for malignancy associated with atypia does not appear to be affected by age.

Authors
Sergesketter, AR; Thomas, SM; Fayanju, OM; Menendez, CS; Rosenberger, LH; Greenup, RA; Hyslop, T; Parrilla Castellar, ER; Hwang, ES; Plichta, JK
MLA Citation
Sergesketter, Amanda R., et al. “The Influence of Age on the Histopathology and Prognosis of Atypical Breast Lesions..” J Surg Res, vol. 241, Sept. 2019, pp. 188–98. Pubmed, doi:10.1016/j.jss.2019.03.047.
PMID
31028940
Source
pubmed
Published In
J Surg Res
Volume
241
Publish Date
2019
Start Page
188
End Page
198
DOI
10.1016/j.jss.2019.03.047

The impact of chemotherapy sequence on survival in node-positive invasive lobular carcinoma.

BACKGROUND AND OBJECTIVES: We sought to evaluate the impact of chemotherapy sequence on survival by comparing node-positive invasive lobular carcinoma (ILC) patients who received neoadjuvant (NACT) and adjuvant (ACT) chemotherapy. METHODS: cT1-4c, cN1-3 ILC patients in the National Cancer Data Base (2004-2013) who underwent surgery and chemotherapy were divided into NACT and ACT cohorts. Kaplan-Meier curves and Cox proportional hazards modeling were used to estimate unadjusted and adjusted overall survival (OS), respectively. RESULTS: Five thousand five hundred fifty-one (35.6%) of 15 573 ILC patients treated with chemotherapy received NACT. NACT patients had similar rates of pT3/4 disease (26.6% vs 26.2%), nodal involvement (median 3 vs 4), and number of lymph nodes examined (median 13 vs 14) but higher rates of mastectomy (81.8% vs 74.5%, P < 0.001) vs ACT patients. 3.4% of NACT patients experienced pathologic complete response (pCR). Unadjusted 10-year OS was worse for NACT vs ACT patients (65.1% vs 54.4%, log-rank P < 0.001). After adjustment for known covariates, NACT continued to be associated with worse OS (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.25-1.52). CONCLUSIONS: In node-positive ILC, NACT yielded low rates of pCR, was not associated with lower rates of mastectomy or less extensive axillary surgery, and was associated with worse survival vs ACT, suggesting limited benefit for these patients.

Authors
Tamirisa, N; Williamson, HV; Thomas, SM; Westbrook, KE; Greenup, RA; Plichta, JK; Rosenberger, LH; Hyslop, T; Hwang, E-SS; Fayanju, OM
MLA Citation
Tamirisa, Nina, et al. “The impact of chemotherapy sequence on survival in node-positive invasive lobular carcinoma..” J Surg Oncol, vol. 120, no. 2, Aug. 2019, pp. 132–41. Pubmed, doi:10.1002/jso.25492.
PMID
31062375
Source
pubmed
Published In
J Surg Oncol
Volume
120
Issue
2
Publish Date
2019
Start Page
132
End Page
141
DOI
10.1002/jso.25492

Incidence of Ductal Carcinoma In Situ in the United States, 2000-2014.

BACKGROUND: In absence of definitive molecular risk markers, clinical management of patients diagnosed with ductal carcinoma in situ (DCIS) remains largely guided by patient and tumor characteristics. In this study, we analyzed recent trends in DCIS incidence and compared them against trends in mammography use. METHODS: The Surveillance, Epidemiology, and End Results registry was queried for patients diagnosed with DCIS from 2000 to 2014 (18 registries). Joinpoint regression analyses were used to compute age- and race-stratified trends in age-adjusted incidence of DCIS. The patterns of DCIS incidence were compared against mammography utilization data from the National Health Interview Survey. RESULTS: Between 2000 and 2014, overall DCIS incidence in the U.S. population was stable (P = 0.24). Among age groups 20 to 44 years and 45 to 55 years, DCIS incidence increased by 1.3% (P = 0.001) and 0.6% (P = 0.02) per year, respectively. Although stable among white women, DCIS incidence increased among black women and women of other races by 1.6% (P < 0.001) and 1.0% (P = 0.002) per year, respectively. Mammography uptake correlated well with DCIS incidence, with the exception of women ages 40 to 49 years and black women who experienced an increase in DCIS incidence despite stagnating and decreasing mammography uptake, respectively. CONCLUSIONS: Overall DCIS incidence rates have remained stable between 2000 and 2014. However, subgroup analyses revealed an increase in incidence among both younger women and black women. IMPACT: DCIS incidence trends did not correlate with the mammography uptake patterns, suggesting that etiologic factors other than screening may be leading to an increased DCIS incidence in these groups.

Authors
Ryser, MD; Hendrix, LH; Worni, M; Liu, Y; Hyslop, T; Hwang, ES
MLA Citation
Ryser, Marc D., et al. “Incidence of Ductal Carcinoma In Situ in the United States, 2000-2014..” Cancer Epidemiol Biomarkers Prev, vol. 28, no. 8, Aug. 2019, pp. 1316–23. Pubmed, doi:10.1158/1055-9965.EPI-18-1262.
PMID
31186262
Source
pubmed
Published In
Cancer Epidemiol Biomarkers Prev
Volume
28
Issue
8
Publish Date
2019
Start Page
1316
End Page
1323
DOI
10.1158/1055-9965.EPI-18-1262

Ductal carcinoma in situ: to treat or not to treat, that is the question.

Ductal carcinoma in situ (DCIS) now represents 20-25% of all 'breast cancers' consequent upon detection by population-based breast cancer screening programmes. Currently, all DCIS lesions are treated, and treatment comprises either mastectomy or breast-conserving surgery supplemented with radiotherapy. However, most DCIS lesions remain indolent. Difficulty in discerning harmless lesions from potentially invasive ones can lead to overtreatment of this condition in many patients. To counter overtreatment and to transform clinical practice, a global, comprehensive and multidisciplinary collaboration is required. Here we review the incidence of DCIS, the perception of risk for developing invasive breast cancer, the current treatment options and the known molecular aspects of progression. Further research is needed to gain new insights for improved diagnosis and management of DCIS, and this is integrated in the PRECISION (PREvent ductal Carcinoma In Situ Invasive Overtreatment Now) initiative. This international effort will seek to determine which DCISs require treatment and prevent the consequences of overtreatment on the lives of many women affected by DCIS.

Authors
van Seijen, M; Lips, EH; Thompson, AM; Nik-Zainal, S; Futreal, A; Hwang, ES; Verschuur, E; Lane, J; Jonkers, J; Rea, DW; Wesseling, J; PRECISION team,
MLA Citation
van Seijen, Maartje, et al. “Ductal carcinoma in situ: to treat or not to treat, that is the question..” Br J Cancer, vol. 121, no. 4, Aug. 2019, pp. 285–92. Pubmed, doi:10.1038/s41416-019-0478-6.
PMID
31285590
Source
pubmed
Published In
Br J Cancer
Volume
121
Issue
4
Publish Date
2019
Start Page
285
End Page
292
DOI
10.1038/s41416-019-0478-6

DCIS with Microinvasion: Is It In Situ or Invasive Disease?

BACKGROUND: Ductal carcinoma in situ (DCIS) with microinvasion (DCISM) can be challenging in balancing the risks of overtreatment versus undertreatment. We compared DCISM, pure DCIS, and small volume (T1a) invasive ductal carcinoma (IDC) as related to histopathology, treatment patterns, and survival outcomes. METHODS: Women ages 18-90 years who underwent breast surgery for DCIS, DCISM, or T1a IDC were selected from the SEER Database (2004-2015). Multivariate logistic regression and Cox proportional hazards models were used to estimate the association of diagnosis with treatment and survival, respectively. RESULTS: A total of 134,569 women were identified: 3.2% DCISM, 70.9% DCIS, and 25.9% with T1a IDC. Compared with invasive disease, DCISM was less likely to be ER+ or PR+ and more likely to be HER2+. After adjustment, DCIS and invasive patients were less likely to undergo mastectomy than DCISM patients (DCIS: OR 0.53, 95% CI 0.49-0.56; invasive: OR 0.86, CI 0.81-0.92). For those undergoing lumpectomy, the likelihood of receiving radiation was similar for DCISM and invasive patients but lower for DCIS patients (OR 0.57, CI 0.52-0.63). After adjustment, breast-cancer-specific survival was significantly different between DCISM and the other two groups (DCIS: HR 0.59, CI 0.43-0.8; invasive: HR 1.43, CI 1.04-1.96). However, overall survival was not significantly different between DCISM and invasive disease, whereas patients with DCIS had improved OS (HR 0.83, CI 0.75-0.93). CONCLUSIONS: Although DCISM is a distinct entity, current treatment patterns and prognosis are comparable to those with small volume IDC. These findings may help providers counsel patients and determine appropriate treatment plans.

Authors
Champion, CD; Ren, Y; Thomas, SM; Fayanju, OM; Rosenberger, LH; Greenup, RA; Menendez, CS; Hwang, ES; Plichta, JK
MLA Citation
Champion, Cosette D., et al. “DCIS with Microinvasion: Is It In Situ or Invasive Disease?.” Ann Surg Oncol, 2019. Pubmed, doi:10.1245/s10434-019-07556-9.
PMID
31342393
Source
pubmed
Published In
Annals of Surgical Oncology
Publish Date
2019
DOI
10.1245/s10434-019-07556-9

Neoadjuvant Endocrine Therapy Versus Neoadjuvant Chemotherapy in Node-Positive Invasive Lobular Carcinoma.

BACKGROUND: Neoadjuvant chemotherapy (NACT) is often recommended for patients with node-positive invasive lobular carcinoma (ILC) despite unclear benefit in this largely hormone receptor-positive (HR+) group. We sought to compare overall survival (OS) between patients with node-positive ILC who received neoadjuvant endocrine therapy (NET) and those who received NACT. METHODS: Women with cT1-4c, cN1-3 HR+ ILC in the National Cancer Data Base (2004-2014) who underwent surgery following neoadjuvant therapy were identified. Kaplan-Meier curves and Cox proportional hazards modeling were used to estimate unadjusted and adjusted overall survival (OS), respectively. RESULTS: Of the 5942 patients in the cohort, 855 received NET and 5087 received NACT. NET recipients were older (70 vs. 54 years) and had more comorbidities (Charlson-Deyo score ≥ 1: 21.1% vs. 11.5%), lower cT classification (cT3-4: 44.2% vs. 51.0%), lower rates of mastectomy (72.5% vs. 82.2%), lower rates of pathologic complete response (0% vs. 2.5%), and lower rates of postlumpectomy (73.2% vs. 91.0%) and postmastectomy (60.0% vs. 80.8%) radiation versus NACT recipients (all p < 0.001). NACT recipients had higher unadjusted 10-year OS versus NET recipients (57.9% vs. 36.0%), but after adjustment, there was no significant difference in OS between the two groups (p = 0.10). CONCLUSIONS: Patients with node-positive ILC who received NET presented with smaller tumors, older age, and greater burden of comorbidities versus NACT recipients but had similar adjusted OS. While there is evidence from clinical trials supporting efficacy of NET in HR+ breast cancer, our findings suggest the need for further, histology-specific investigation regarding the optimal inclusion and sequence of endocrine therapy and chemotherapy in ILC.

Authors
Thornton, MJ; Williamson, HV; Westbrook, KE; Greenup, RA; Plichta, JK; Rosenberger, LH; Gupta, AM; Hyslop, T; Hwang, ES; Fayanju, OM
MLA Citation
Thornton, M. J., et al. “Neoadjuvant Endocrine Therapy Versus Neoadjuvant Chemotherapy in Node-Positive Invasive Lobular Carcinoma..” Ann Surg Oncol, 2019. Pubmed, doi:10.1245/s10434-019-07564-9.
PMID
31342392
Source
pubmed
Published In
Annals of Surgical Oncology
Publish Date
2019
DOI
10.1245/s10434-019-07564-9

Perspectives on the Costs of Cancer Care: A Survey of the American Society of Breast Surgeons.

BACKGROUND: Cancer treatment costs are not routinely addressed in shared decisions for breast cancer surgery. Thus, we sought to characterize cost awareness and communication among surgeons treating breast cancer. METHODS: We conducted a self-administered, confidential electronic survey among members of the American Society of Breast Surgeons from 1 July to 15 September 2018. Questions were based on previously published or validated survey items, and assessed surgeon demographics, cost sensitivity, and communication. Descriptive summaries and cross-tabulations with Chi-square statistics were used, with exact tests where warranted, to assess findings. RESULTS: Of those surveyed (N = 2293), 598 (25%) responded. Surgeons reported that 'risk of recurrence' (70%), 'appearance of the breast' (50%), and 'risks of surgery' (47%) were the most influential on patients' decisions for breast cancer surgery; 6% cited out-of-pocket costs as significant. Over half (53%) of the surgeons agreed that doctors should consider patient costs when choosing cancer treatment, yet the majority of surgeons (58%) reported 'infrequently' (43%) or 'never' (15%) considering patient costs in medical recommendations. The overwhelming majority (87%) of surgeons believed that patients should have access to the costs of their treatment before making medical decisions. Surgeons treating a higher percentage of Medicaid or uninsured patients were more likely to consistently consider costs (p < 0.001). Participants reported that insufficient knowledge or resources (61%), a perceived inability to help with costs (24%), and inadequate time (22%) impeded cost discussions. Notably, 20% of participants believed that discussing costs might impact the quality of care patients receive. CONCLUSIONS: Cost transparency remains rare, however in shared decisions for breast cancer surgery, improved cost awareness by surgeons has the potential to reduce financial hardship.

Authors
Greenup, RA; Rushing, CN; Fish, LJ; Lane, WO; Peppercorn, JM; Bellavance, E; Tolnitch, L; Hyslop, T; Myers, ER; Zafar, SY; Hwang, ES
MLA Citation
Greenup, Rachel A., et al. “Perspectives on the Costs of Cancer Care: A Survey of the American Society of Breast Surgeons..” Ann Surg Oncol, 2019. Pubmed, doi:10.1245/s10434-019-07594-3.
PMID
31342390
Source
pubmed
Published In
Annals of Surgical Oncology
Publish Date
2019
DOI
10.1245/s10434-019-07594-3

Decreasing rates of axillary lymph node dissections over time: Implications for surgical resident exposure and operative skills development.

BACKGROUND: Sentinel lymph node biopsy has supplanted axillary lymph node dissection (ALND) in clinically node-negative breast cancer and select node-positive disease. We hypothesized a decreasing rate of both ALND and resident exposure over time. METHODS: We identified women with clinical Stage I-III breast cancer in the National Cancer Data Base (2004-2014). Adjusted multivariate logistic regression was used to estimate the effect of various factors on receipt of ALND. Yearly procedural rates for residents were extracted from surgical case log reports for comparison against procedural rates. RESULTS: 1,131,363 patients were identified; 255,306 received ALND, 876,057 underwent non-ALND management. ALND rates declined from 2004 (32%) to 2014 (16%, p < 0.001), with the largest decline occurring between 2010 and 2011 (24%-20%). After adjustment, this effect was maintained, with ALND rates decreasing with each additional year (OR = 0.90, 95% CI 0.89-0.90). Resident procedure volumes similarly declined from 1999 to 2017 (p < 0.001). CONCLUSIONS: Significant declines in both ALND rates and procedural volume in residency may impact outcomes, as ALNDs are being performed in ever more challenging oncologic scenarios by potentially less-experienced surgeons.

Authors
Rosenberger, LH; Thomas, SM; Plichta, JK; Fayanju, OM; Hyslop, T; Greenup, RA; Hwang, ES
MLA Citation
Rosenberger, Laura H., et al. “Decreasing rates of axillary lymph node dissections over time: Implications for surgical resident exposure and operative skills development..” Am J Surg, 2019. Pubmed, doi:10.1016/j.amjsurg.2019.07.013.
PMID
31350006
Source
pubmed
Published In
Am J Surg
Publish Date
2019
DOI
10.1016/j.amjsurg.2019.07.013

Clinical and pathological stage discordance among 433,514 breast cancer patients.

BACKGROUND: We aim to determine clinical and pathological stage discordance rates and to evaluate factors associated with discordance. METHODS: Adults with clinical stages I-III breast cancer were identified from the National Cancer Data Base. Concordance was defined as cTN = pTN (discordance: cTN≠pTN). Multivariate logistic regression was used to identify factors associated with discordance. RESULTS: Comparing clinical and pathological stage, 23.1% were downstaged and 8.7% were upstaged. After adjustment, factors associated with downstaging (vs concordance) included grade 3 (OR 10.56, vs grade 1) and HER2-negative (OR 3.79). Factors associated with upstaging (vs concordance) were grade 3 (OR 10.56, vs grade 1), HER2-negative (OR 1.25), and lobular histology (OR 2.47, vs ductal). ER-negative status was associated with stage concordance (vs downstaged or upstaged, OR 0.52 and 0.87). CONCLUSIONS: Among breast cancer patients, nearly one-third exhibit clinical-pathological stage discordance. This high likelihood of discordance is important to consider for counseling and treatment planning.

Authors
Plichta, JK; Thomas, SM; Sergesketter, AR; Greenup, RA; Fayanju, OM; Rosenberger, LH; Tamirisa, N; Hyslop, T; Hwang, ES
MLA Citation
Plichta, Jennifer K., et al. “Clinical and pathological stage discordance among 433,514 breast cancer patients..” Am J Surg, July 2019. Pubmed, doi:10.1016/j.amjsurg.2019.07.016.
PMID
31350005
Source
pubmed
Published In
Am J Surg
Publish Date
2019
DOI
10.1016/j.amjsurg.2019.07.016

Growth Dynamics of Mammographic Calcifications: Differentiating Ductal Carcinoma in Situ from Benign Breast Disease.

Background Most ductal carcinoma in situ (DCIS) lesions are first detected on screening mammograms as calcifications. However, false-positive biopsy rates for calcifications range from 30% to 87%. Improved methods to differentiate benign from malignant calcifications are thus needed. Purpose To quantify the growth rates of DCIS and benign breast disease that manifest as mammographic calcifications. Materials and Methods All calcifications (n = 2359) for which a stereotactic biopsy was performed from 2008 through 2015 at Duke University Medical Center were retrospectively identified. Mammograms from all cases of DCIS (n = 404) were reviewed for calcifications that were visible on mammograms taken at least 6 months before biopsy. Women with at least one prior mammogram with visible calcifications were age- and race-matched 1:2 to women with a benign breast biopsy and calcifications visible on prior mammograms. The long axis of the calcifications was measured on all mammograms. Multivariable adjusted linear mixed-effects models estimated the association of calcification growth rates with patholo findings. Hierarchical clustering accounted for matching benign and DCIS groups. Results A total of 74 DCIS calcifications and 148 benign calcifications were included for final analysis. The median patient age was 62 years (interquartile range, 51-71 years). No significant difference in breast density (P > .05) or number of available mammograms (P > .05) was detected between groups. Calcifications associated with DCIS were larger than those associated with benign breast disease at biopsy (median, 10 mm vs 6 mm, respectively; P < .001). After adjustment, the relative annual increase in the long-axis length of DCIS calcifications was greater than that of benign breast calcifications (96% [95% confidence interval: 72%, 224%] vs 68% [95% confidence interval: 56%, 80%] per year, respectively; P < .001). Conclusion Ductal carcinoma in situ calcifications are more extensive at diagnosis and grow faster in extent than those associated with benign breast disease. The rate of calcification change may help to discriminate benign from malignant calcifications. © RSNA, 2019 Online supplemental material is available for this article.

Authors
Grimm, LJ; Miller, MM; Thomas, SM; Liu, Y; Lo, JY; Hwang, ES; Hyslop, T; Ryser, MD
MLA Citation
Grimm, Lars J., et al. “Growth Dynamics of Mammographic Calcifications: Differentiating Ductal Carcinoma in Situ from Benign Breast Disease..” Radiology, vol. 292, no. 1, July 2019, pp. 77–83. Pubmed, doi:10.1148/radiol.2019182599.
PMID
31112087
Source
pubmed
Published In
Radiology
Volume
292
Issue
1
Publish Date
2019
Start Page
77
End Page
83
DOI
10.1148/radiol.2019182599

Response to Habel and Buist.

Authors
Ryser, MD; Hwang, ES
MLA Citation
Ryser, Marc D., and E. Shelley Hwang. “Response to Habel and Buist..” J Natl Cancer Inst, June 2019. Pubmed, doi:10.1093/jnci/djz120.
PMID
31199468
Source
pubmed
Published In
J Natl Cancer Inst
Publish Date
2019
DOI
10.1093/jnci/djz120

Synchronous Detection of Circulating Tumor Cells in Blood and Disseminated Tumor Cells in Bone Marrow Predicts Adverse Outcome in Early Breast Cancer.

Purpose: We examined the prognostic impact of circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) detected at the time of surgery in 742 untreated patients with early breast cancer.Experimental Design: DTCs in bone marrow were enumerated using the EPCAM-based immunomagnetic enrichment and flow cytometry (IE/FC) assay. CTCs in blood were enumerated either by IE/FC or CellSearch. Median follow-up was 7.1 years for distant recurrence-free survival (DRFS) and 9.1 years for breast cancer-specific survival (BCSS) and overall survival (OS). Cox regressions were used to estimate hazard ratios for DRFS, BCSS, and OS in all patients, as well as in hormone receptor-positive (HR-positive, 87%) and HR-negative (13%) subsets.Results: In multivariate models, CTC positivity by IE/FC was significantly associated with reduced BCSS in both all (n = 288; P = 0.0138) and HR-positive patients (n = 249; P = 0.0454). CTC positivity by CellSearch was significantly associated with reduced DRFS in both all (n = 380; P = 0.0067) and HR-positive patients (n = 328; P = 0.0002). DTC status, by itself, was not prognostic; however, when combined with CTC status by IE/FC (n = 273), double positivity (CTC+/DTC+, 8%) was significantly associated with reduced DRFS (P = 0.0270), BCSS (P = 0.0205), and OS (P = 0.0168). In HR-positive patients, double positivity (9% of 235) was significantly associated with reduced DRFS (P = 0.0285), BCSS (P = 0.0357), and OS (P = 0.0092).Conclusions: Detection of CTCs in patients with HR-positive early breast cancer was an independent prognostic factor for DRFS (using CellSearch) and BCSS (using IE/FC). Simultaneous detection of DTCs provided additional prognostic power for outcome, including OS.

Authors
Magbanua, MJM; Yau, C; Wolf, DM; Lee, JS; Chattopadhyay, A; Scott, JH; Bowlby-Yoder, E; Hwang, ES; Alvarado, M; Ewing, CA; Delson, AL; Van't Veer, LJ; Esserman, L; Park, JW
MLA Citation
Magbanua, Mark Jesus M., et al. “Synchronous Detection of Circulating Tumor Cells in Blood and Disseminated Tumor Cells in Bone Marrow Predicts Adverse Outcome in Early Breast Cancer..” Clin Cancer Res, May 2019. Pubmed, doi:10.1158/1078-0432.CCR-18-3888.
PMID
31142502
Source
pubmed
Published In
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Publish Date
2019
DOI
10.1158/1078-0432.CCR-18-3888

Anxiety scores of women with an increased risk of breast cancer participating in facilitated group visits

Authors
Trotter, K; Plichta, J; Hwang, ES; Reynolds, H
MLA Citation
Trotter, Kathryn, et al. “Anxiety scores of women with an increased risk of breast cancer participating in facilitated group visits.” Annals of Surgical Oncology, vol. 26, SPRINGER, 2019, pp. 137–38.
Source
wos
Published In
Annals of Surgical Oncology
Volume
26
Publish Date
2019
Start Page
137
End Page
138

Human Tumor-Associated Macrophage and Monocyte Transcriptional Landscapes Reveal Cancer-Specific Reprogramming, Biomarkers, and Therapeutic Targets.

The roles of tumor-associated macrophages (TAMs) and circulating monocytes in human cancer are poorly understood. Here, we show that monocyte subpopulation distribution and transcriptomes are significantly altered by the presence of endometrial and breast cancer. Furthermore, TAMs from endometrial and breast cancers are transcriptionally distinct from monocytes and their respective tissue-resident macrophages. We identified a breast TAM signature that is highly enriched in aggressive breast cancer subtypes and associated with shorter disease-specific survival. We also identified an auto-regulatory loop between TAMs and cancer cells driven by tumor necrosis factor alpha involving SIGLEC1 and CCL8, which is self-reinforcing through the production of CSF1. Together these data provide direct evidence that monocyte and macrophage transcriptional landscapes are perturbed by cancer, reflecting patient outcomes.

Authors
Cassetta, L; Fragkogianni, S; Sims, AH; Swierczak, A; Forrester, LM; Zhang, H; Soong, DYH; Cotechini, T; Anur, P; Lin, EY; Fidanza, A; Lopez-Yrigoyen, M; Millar, MR; Urman, A; Ai, Z; Spellman, PT; Hwang, ES; Dixon, JM; Wiechmann, L; Coussens, LM; Smith, HO; Pollard, JW
MLA Citation
Cassetta, Luca, et al. “Human Tumor-Associated Macrophage and Monocyte Transcriptional Landscapes Reveal Cancer-Specific Reprogramming, Biomarkers, and Therapeutic Targets..” Cancer Cell, vol. 35, no. 4, Apr. 2019, pp. 588-602.e10. Pubmed, doi:10.1016/j.ccell.2019.02.009.
PMID
30930117
Source
pubmed
Published In
Cancer Cell
Volume
35
Issue
4
Publish Date
2019
Start Page
588
End Page
602.e10
DOI
10.1016/j.ccell.2019.02.009

Variability in diagnostic threshold for comedo necrosis among breast pathologists: implications for patient eligibility for active surveillance trials of ductal carcinoma in situ.

Active surveillance trials for low-risk ductal carcinoma in situ (DCIS) are in progress in the United States and Europe. In some of these trials, the presence of comedo necrosis in the DCIS has been an exclusion criterion for trial entry. However, the minimum amount of necrosis required by pathologists for a diagnosis of comedo necrosis is not well-defined. We surveyed 35 experienced breast pathologists to assess their diagnostic threshold for comedo necrosis. Pink circles representing necrosis ranging in extent from 10 to 80% of the duct diameter were superimposed on eight replicate histologic images of a single duct involved by low nuclear grade, solid pattern DCIS. These images were circulated by e-mail to the participating pathologists who were asked to select the image that represents the minimum amount of necrosis that they require for a diagnosis of comedo necrosis. Among the 35 participants, the minimum extent of the duct diameter required for a diagnosis of comedo necrosis was 10% for 4 pathologists, 20% for 5, 30% for 11, 40% for 7, 50% for 6, 60% for 1 and 70% for 1. There was no single threshold about which more than one-third of the pathologists agreed met the minimal criteria for comedo necrosis. We conclude that even among experienced breast pathologists, the threshold for comedo necrosis is highly variable. Our findings highlight the need for a standardized definition of comedo necrosis as a trial criterion, and more generally where it may be used as a marker of increased risk of recurrence for therapeutic decision making.

Authors
Harrison, BT; Hwang, ES; Partridge, AH; Thompson, AM; Schnitt, SJ
MLA Citation
Harrison, Beth T., et al. “Variability in diagnostic threshold for comedo necrosis among breast pathologists: implications for patient eligibility for active surveillance trials of ductal carcinoma in situ..” Mod Pathol, 2019. Pubmed, doi:10.1038/s41379-019-0262-4.
PMID
30980039
Source
pubmed
Published In
Modern Pathology
Publish Date
2019
DOI
10.1038/s41379-019-0262-4

The COMET (Comparison of Operative versus Monitoring and Endocrine Therapy) trial: a phase III randomised controlled clinical trial for low-risk ductal carcinoma in situ (DCIS).

INTRODUCTION: Ductal carcinoma in situ (DCIS) is a non-invasive non-obligate precursor of invasive breast cancer. With guideline concordant care (GCC), DCIS outcomes are at least as favourable as some other early stage cancer types such as prostate cancer, for which active surveillance (AS) is a standard of care option. However, AS has not yet been tested in relation to DCIS. The goal of the COMET (Comparison of Operative versus Monitoring and Endocrine Therapy) trial for low-risk DCIS is to gather evidence to help future patients consider the range of treatment choices for low-risk DCIS, from standard therapies to AS. The trial will determine whether there may be some women who do not substantially benefit from current GCC and who could thus be safely managed with AS. This protocol is version 5 (11 July 2018). Any future protocol amendments will be submitted to Quorum Centralised Institutional Review Board/local institutional review boards for approval via the sponsor of the study (Alliance Foundation Trials). METHODS AND ANALYSIS: COMET is a phase III, randomised controlled clinical trial for patients with low-risk DCIS. The primary outcome is ipsilateral invasive breast cancer rate in women undergoing GCC compared with AS. Secondary objectives will be to compare surgical, oncological and patient-reported outcomes. Patients randomised to the GCC group will undergo surgery as well as radiotherapy when appropriate; those in the AS group will be monitored closely with surgery only on identification of invasive breast cancer. Patients in both the GCC and AS groups will have the option of endocrine therapy. The total planned accrual goal is 1200 patients. ETHICS AND DISSEMINATION: The COMET trial will be subject to biannual formal review at the Alliance Foundation Data Safety Monitoring Board meetings. Interim analyses for futility/safety will be completed annually, with reporting following Consolidated Standards of Reporting Trials (CONSORT) guidelines for non-inferiority trials. TRIAL REGISTRATION NUMBER: NCT02926911; Pre-results.

Authors
Hwang, ES; Hyslop, T; Lynch, T; Frank, E; Pinto, D; Basila, D; Collyar, D; Bennett, A; Kaplan, C; Rosenberg, S; Thompson, A; Weiss, A; Partridge, A
MLA Citation
Hwang, E. Shelley, et al. “The COMET (Comparison of Operative versus Monitoring and Endocrine Therapy) trial: a phase III randomised controlled clinical trial for low-risk ductal carcinoma in situ (DCIS)..” Bmj Open, vol. 9, no. 3, Mar. 2019. Pubmed, doi:10.1136/bmjopen-2018-026797.
PMID
30862637
Source
pubmed
Published In
Bmj Open
Volume
9
Issue
3
Publish Date
2019
Start Page
e026797
DOI
10.1136/bmjopen-2018-026797

Surgical Resection of the Primary Tumor in Women With De Novo Stage IV Breast Cancer: Contemporary Practice Patterns and Survival Analysis.

OBJECTIVE: We evaluated patterns of surgical care and their association with overall survival among a contemporary cohort of women with stage IV breast cancer. BACKGROUND: Surgical resection of the primary tumor remains controversial among women with stage IV breast cancer. METHODS: Women diagnosed with clinical stage IV breast cancer from 2003 to 2012 were identified from the American College of Surgeons National Cancer Database. Those with intact primary tumors who were alive 12 months after diagnosis were categorized by treatment sequence: (1) surgery before systemic therapy, (2) systemic therapy before surgery, and (3) systemic therapy alone. Multivariate logistic regression was used to estimate the association of treatment sequence with surgery type. Overall survival was estimated using multivariate Cox proportional hazards models. RESULTS: Among 24,015 women, 56.2% (13,505) underwent systemic therapy alone and 43.8% (10,510) underwent surgical resection. Rates of surgery decreased slightly over time (43.1% in 2003 to 41.9% in 2011). Treatment with systemic therapy before surgery was associated with larger tumor size (median 4.5 vs 3.1 cm, P < 0.001) and receipt of mastectomy (81.4% vs 52.2%, P < 0.001) when compared to those who underwent surgery first. Receipt of surgery, whether before or after systemic therapy (Hazard Ratio, 0.68; 95% confidence interval, 0.62-0.73; Hazard Ratio, 0.56; 95% confidence interval, 0.52-0.61; P < 0.001), was independently associated with improved adjusted overall survival when compared to systemic therapy alone. CONCLUSIONS: Surgical resection of the primary tumor occurs in almost half of women with stage IV breast cancer alive 1 year after diagnosis, and is increasingly occurring after systemic therapy. Coordinated multidisciplinary care remains highly relevant in the setting of metastatic breast cancer, where surgical decisions should be made on an individual basis and may affect survival in select women.

Authors
Lane, WO; Thomas, SM; Blitzblau, RC; Plichta, JK; Rosenberger, LH; Fayanju, OM; Hyslop, T; Hwang, ES; Greenup, RA
MLA Citation
Lane, Whitney O., et al. “Surgical Resection of the Primary Tumor in Women With De Novo Stage IV Breast Cancer: Contemporary Practice Patterns and Survival Analysis..” Ann Surg, vol. 269, no. 3, Mar. 2019, pp. 537–44. Pubmed, doi:10.1097/SLA.0000000000002621.
PMID
29227346
Source
pubmed
Published In
Ann Surg
Volume
269
Issue
3
Publish Date
2019
Start Page
537
End Page
544
DOI
10.1097/SLA.0000000000002621

A National Snapshot of Patient-Reported Outcomes Comparing Types of Abdominal Flaps for Breast Reconstruction.

BACKGROUND: This study aimed to identify differences in patient-reported abdominal well-being, satisfaction, and quality of life in women with muscle-preserving free abdominal versus pedicle transverse rectus abdominis musculocutaneous (TRAM) flap for breast reconstruction. METHODS: Women with a history of breast cancer surgery were recruited from the Army of Women foundation to take the BREAST-Q and a background questionnaire. Descriptive statistics and regression analyses were used to compare abdominal physical well-being, breast satisfaction, chest physical, psychosocial well-being, and sexual well-being in women undergoing free versus pedicle TRAM flaps. RESULTS: Of 657 women, 273 (41 percent) underwent free flap surgery and 384 (58 percent) underwent pedicle TRAM flap surgery. Compared with unilateral pedicle TRAM flaps, those with unilateral free flaps scored an average of 9.5 points higher (95 percent CI, 5.4 to 13.6; p < 0.0001) and those with bilateral free flaps reported no difference in physical well-being of the abdomen. Compared with bilateral pedicle TRAM flaps, the following groups scored higher in physical well-being of the abdomen: unilateral free flaps, an average of 17.4 (95 percent CI, 11.5 to 23.3; p < 0.0001); bilateral free flaps, an average of 6.8 (95 percent CI, 0.3 to 13.3; p = 0.04); and unilateral pedicle TRAM flaps, an average of 7.9 (95 percent CI, 2.4 to 13.4; p = 0.005) higher. Women with bilateral pedicle flaps reported sexual well-being scores 7.4 (95 percent CI, 0.6 to 14.3; p = 0.03) and 6.8 (95 percent CI, 0.3 to 13.2; p = 0.04) points lower than those with unilateral free and unilateral pedicle flaps. CONCLUSIONS: Muscle-preserving techniques result in improved abdominal wall function and decreased morbidity compared with pedicle TRAM flap reconstruction. These data highlight the importance of offering patients the option of microsurgical techniques.

Authors
Atisha, DM; Tessiatore, KM; Rushing, CN; Dayicioglu, D; Pusic, A; Hwang, S
MLA Citation
Atisha, Dunya M., et al. “A National Snapshot of Patient-Reported Outcomes Comparing Types of Abdominal Flaps for Breast Reconstruction..” Plast Reconstr Surg, vol. 143, no. 3, Mar. 2019, pp. 667–77. Pubmed, doi:10.1097/PRS.0000000000005301.
PMID
30589826
Source
pubmed
Published In
Plast Reconstr Surg
Volume
143
Issue
3
Publish Date
2019
Start Page
667
End Page
677
DOI
10.1097/PRS.0000000000005301

Cancer Outcomes in DCIS Patients Without Locoregional Treatment.

Background: The vast majority of women diagnosed with ductal carcinoma in situ (DCIS) undergo treatment. Therefore, the risks of invasive progression and competing death in the absence of locoregional therapy are uncertain. Methods: We performed survival analyses of patient-level data from DCIS patients who did not receive definitive surgery or radiation therapy as recorded in the US National Cancer Institute's Surveillance, Epidemiology, and End Results program (1992-2014). Kaplan-Meier curves were used to estimate the net risk of subsequent ipsilateral invasive cancer. The cumulative incidences of ipsilateral invasive cancer, contralateral breast cancer, and death were estimated using competing risk methods. Results: A total of 1286 DCIS patients who did not undergo locoregional therapy were identified. Median age at diagnosis was 60 years (inter-quartile range = 51-74 years), with median follow-up of 5.5 years (inter-quartile range = 2.3-10.6 years). Among patients with tumor grade I/II (n = 547), the 10-year net risk of ipsilateral invasive breast cancer was 12.2% (95% confidence interval [CI] = 8.6% to 17.1%) compared with 17.6% (95% CI = 12.1% to 25.2%) among patients with tumor grade III (n = 244) and 10.1% (95% CI = 7.4% to 13.8%) among patients with unknown grade (n = 495). Among all patients, the 10-year cumulative incidences of ipsilateral invasive cancer, contralateral breast cancer, and all-cause mortality were 10.5% (95% CI = 8.5% to 12.4%), 3.9% (95% CI = 2.6% to 5.2%), and 24.1% (95% CI = 21.2% to 26.9%), respectively. Conclusion: Despite limited data, our findings suggest that DCIS patients without locoregional treatment have a limited risk of invasive progression. Although the cohort is not representative of the general population of patients diagnosed with DCIS, the findings suggest that there may be overtreatment, especially among older patients and patients with elevated comorbidities.

Authors
Ryser, MD; Weaver, DL; Zhao, F; Worni, M; Grimm, LJ; Gulati, R; Etzioni, R; Hyslop, T; Lee, SJ; Hwang, ES
MLA Citation
Ryser, Marc D., et al. “Cancer Outcomes in DCIS Patients Without Locoregional Treatment..” J Natl Cancer Inst, Feb. 2019. Pubmed, doi:10.1093/jnci/djy220.
PMID
30759222
Source
pubmed
Published In
J Natl Cancer Inst
Publish Date
2019
DOI
10.1093/jnci/djy220

Reframing the conversation about contralateral prophylactic mastectomy: Preparing women for postsurgical realities.

OBJECTIVE: Women with unilateral, early-stage breast cancer and low genetic risk are increasingly opting for contralateral prophylactic mastectomy (CPM), a concerning trend because CPM offers few clinical benefits while increasing risks of surgical complications. Few qualitative studies have analyzed factors motivating this irreversible decision. Using qualitative methods, this study sought to understand women's decision making and the impact of CPM on self-confidence, sense of femininity, sexual intimacy, and peace of mind. METHODS: Women who had CPM within the last 10 years were recruited to participate in the study. We conducted a thematic analysis of the data. RESULTS: Forty-five women were interviewed. When making the decision for CPM, most had incomplete knowledge of potential negative outcomes. However, all believed CPM had more benefits than harms and would confer the most peace of mind and the fewest regrets should cancer return. They knew their contralateral breast cancer risk was low but were not persuaded by statistics. They wanted to do everything possible to reduce their risk of another breast cancer, even by a minimal amount, but most reported paying an unexpectedly high price for this small reduction in risk. Nevertheless, 41 of 45 reported that they would make the same decision again. CONCLUSIONS: These findings highlight an opportunity for physicians to reframe the conversation to focus on the patient experience of the tradeoffs of CPM rather than statistical odds of future cancers. Our findings suggest that more data may not dissuade women from CPM but may better prepare them for its outcomes.

Authors
Bloom, DL; Chapman, BM; Wheeler, SB; McGuire, KP; Lee, CN; Weinfurt, K; Rosenstein, DL; Plichta, JK; Jacobson Vann, JC; Hwang, ES
MLA Citation
Bloom, Diane L., et al. “Reframing the conversation about contralateral prophylactic mastectomy: Preparing women for postsurgical realities..” Psychooncology, vol. 28, no. 2, 2019, pp. 394–400. Pubmed, doi:10.1002/pon.4955.
PMID
30500102
Source
pubmed
Published In
Psychooncology
Volume
28
Issue
2
Publish Date
2019
Start Page
394
End Page
400
DOI
10.1002/pon.4955

Risk factors for severe acute pain and persistent pain after surgery for breast cancer: a prospective observational study.

BACKGROUND AND OBJECTIVES: There are few prospective studies providing comprehensive assessment of risk factors for acute and persistent pain after breast surgery. This prospective observational study assessed patient-related, perioperative, and genetic risk factors for severe acute pain and persistent pain following breast cancer surgery. METHODS: Women presenting for elective breast cancer surgery completed State Trait Anxiety Inventory, Beck Depression Inventory, and Pain Catastrophizing Scale questionnaires preoperatively. Diffuse noxious inhibitory control and mechanical temporal summation were assessed. A blood sample was obtained for genetic analysis. Analgesic consumption and pain scores were collected in the post-anesthesia care unit, and at 24 and 72 hours. Patients were contacted at 1, 3, 6, and 12 months to assess persistent pain. Primary outcome was maximum acute pain score in first 72 hours and secondary outcome was persistent pain. RESULTS: One hundred twenty-four patients were included in analysis. Increased duration of surgery, surgeon, and higher pain catastrophizing scores were associated with increased severity of acute pain, while preoperative radiotherapy was associated with reduced severity. Persistent pain was reported by 57.3% of patients. Postdischarge chemotherapy (OR 2.52, 95% CI 1.13 to 5.82), postdischarge radiation (OR 3.39, 95% CI 1.24 to 10.41), severe acute pain (OR 5.39, 95% CI 2.03 to 15.54), and moderate acute pain (OR 5.31, 95% CI 1.99 to 15.30) were associated with increased likelihood of persistent pain. CONCLUSIONS: Increased duration of surgery, higher pain catastrophizing score, and surgeon were associated with increased severity of acute pain. Preoperative radiation was associated with lower acute pain scores. Postsurgery radiation, chemotherapy, and severity of acute pain were associated with increased likelihood of persistent pain. TRIAL REGISTRATION: NCT03307525.

Authors
Habib, AS; Kertai, MD; Cooter, M; Greenup, RA; Hwang, S
MLA Citation
Habib, Ashraf S., et al. “Risk factors for severe acute pain and persistent pain after surgery for breast cancer: a prospective observational study..” Reg Anesth Pain Med, vol. 44, no. 2, Feb. 2019, pp. 192–99. Pubmed, doi:10.1136/rapm-2018-000040.
PMID
30700614
Source
pubmed
Published In
Regional Anesthesia and Pain Medicine
Volume
44
Issue
2
Publish Date
2019
Start Page
192
End Page
199
DOI
10.1136/rapm-2018-000040

Identification of the Fraction of Indolent Tumors and Associated Overdiagnosis in Breast Cancer Screening Trials.

It is generally accepted that some screen-detected breast cancers are overdiagnosed and would not progress to symptomatic cancer if left untreated. However, precise estimates of the fraction of nonprogressive cancers remain elusive. In recognition of the weaknesses of overdiagnosis estimation methods based on excess incidence, there is a need for model-based approaches that accommodate nonprogressive lesions. Here, we present an in-depth analysis of a generalized model of breast cancer natural history that allows for a mixture of progressive and indolent lesions. We provide a formal proof of global structural identifiability of the model and use simulation to identify conditions that allow for parameter estimates that are sufficiently precise and practically actionable. We show that clinical follow-up after the last screening can play a critical role in ensuring adequately precise identification of the fraction of indolent cancers in a stop-screen trial design, and we demonstrate that model misspecification can lead to substantially biased estimates of mean sojourn time. Finally, we illustrate our findings using the example of Canadian National Breast Screening Study 2 (1980-1985) and show that the fraction of indolent cancers is not precisely identifiable. Our findings provide the foundation for extended models that account for both in situ and invasive lesions.

Authors
Ryser, MD; Gulati, R; Eisenberg, MC; Shen, Y; Hwang, ES; Etzioni, RB
MLA Citation
Ryser, Marc D., et al. “Identification of the Fraction of Indolent Tumors and Associated Overdiagnosis in Breast Cancer Screening Trials..” Am J Epidemiol, vol. 188, no. 1, Jan. 2019, pp. 197–205. Pubmed, doi:10.1093/aje/kwy214.
PMID
30325415
Source
pubmed
Published In
American Journal of Epidemiology
Volume
188
Issue
1
Publish Date
2019
Start Page
197
End Page
205
DOI
10.1093/aje/kwy214

Effect of Linagliptin vs Placebo on Major Cardiovascular Events in Adults With Type 2 Diabetes and High Cardiovascular and Renal Risk: The CARMELINA Randomized Clinical Trial.

Importance: Type 2 diabetes is associated with increased cardiovascular (CV) risk. Prior trials have demonstrated CV safety of 3 dipeptidyl peptidase 4 (DPP-4) inhibitors but have included limited numbers of patients with high CV risk and chronic kidney disease. Objective: To evaluate the effect of linagliptin, a selective DPP-4 inhibitor, on CV outcomes and kidney outcomes in patients with type 2 diabetes at high risk of CV and kidney events. Design, Setting, and Participants: Randomized, placebo-controlled, multicenter noninferiority trial conducted from August 2013 to August 2016 at 605 clinic sites in 27 countries among adults with type 2 diabetes, hemoglobin A1c of 6.5% to 10.0%, high CV risk (history of vascular disease and urine-albumin creatinine ratio [UACR] >200 mg/g), and high renal risk (reduced eGFR and micro- or macroalbuminuria). Participants with end-stage renal disease (ESRD) were excluded. Final follow-up occurred on January 18, 2018. Interventions: Patients were randomized to receive linagliptin, 5 mg once daily (n = 3494), or placebo once daily (n = 3485) added to usual care. Other glucose-lowering medications or insulin could be added based on clinical need and local clinical guidelines. Main Outcomes and Measures: Primary outcome was time to first occurrence of the composite of CV death, nonfatal myocardial infarction, or nonfatal stroke. Criteria for noninferiority of linagliptin vs placebo was defined by the upper limit of the 2-sided 95% CI for the hazard ratio (HR) of linagliptin relative to placebo being less than 1.3. Secondary outcome was time to first occurrence of adjudicated death due to renal failure, ESRD, or sustained 40% or higher decrease in eGFR from baseline. Results: Of 6991 enrollees, 6979 (mean age, 65.9 years; eGFR, 54.6 mL/min/1.73 m2; 80.1% with UACR >30 mg/g) received at least 1 dose of study medication and 98.7% completed the study. During a median follow-up of 2.2 years, the primary outcome occurred in 434 of 3494 (12.4%) and 420 of 3485 (12.1%) in the linagliptin and placebo groups, respectively, (absolute incidence rate difference, 0.13 [95% CI, -0.63 to 0.90] per 100 person-years) (HR, 1.02; 95% CI, 0.89-1.17; P < .001 for noninferiority). The kidney outcome occurred in 327 of 3494 (9.4%) and 306 of 3485 (8.8%), respectively (absolute incidence rate difference, 0.22 [95% CI, -0.52 to 0.97] per 100 person-years) (HR, 1.04; 95% CI, 0.89-1.22; P = .62). Adverse events occurred in 2697 (77.2%) and 2723 (78.1%) patients in the linagliptin and placebo groups; 1036 (29.7%) and 1024 (29.4%) had 1 or more episodes of hypoglycemia; and there were 9 (0.3%) vs 5 (0.1%) events of adjudication-confirmed acute pancreatitis. Conclusions and Relevance: Among adults with type 2 diabetes and high CV and renal risk, linagliptin added to usual care compared with placebo added to usual care resulted in a noninferior risk of a composite CV outcome over a median 2.2 years. Trial Registration: ClinicalTrials.gov Identifier: NCT01897532.

Authors
Rosenstock, J; Perkovic, V; Johansen, OE; Cooper, ME; Kahn, SE; Marx, N; Alexander, JH; Pencina, M; Toto, RD; Wanner, C; Zinman, B; Woerle, HJ; Baanstra, D; Pfarr, E; Schnaidt, S; Meinicke, T; George, JT; von Eynatten, M; McGuire, DK; CARMELINA Investigators,
MLA Citation
Rosenstock, Julio, et al. “Effect of Linagliptin vs Placebo on Major Cardiovascular Events in Adults With Type 2 Diabetes and High Cardiovascular and Renal Risk: The CARMELINA Randomized Clinical Trial..” Jama, vol. 321, no. 1, Jan. 2019, pp. 69–79. Pubmed, doi:10.1001/jama.2018.18269.
PMID
30418475
Source
pubmed
Published In
Jama
Volume
321
Issue
1
Publish Date
2019
Start Page
69
End Page
79
DOI
10.1001/jama.2018.18269

Malignant microcalcification clusters detection using unsupervised deep autoencoders

© 2019 SPIE. Detection and localization of microcalcification (MC) clusters are very important in mammography diagnosis. Supervised MC detectors require learning from extracted individual MCs and MC clusters. However, they are limited by number of datasets given that MC images are hard to obtain. In this work, we propose a method to detect malignant microcalcification (MC) clusters using unsupervised, one-class, deep convolutional autoencoder. Specifically, we designed a deep autoencoder model where only patches extracted from normal cases' mammograms are used during training. We then applied our trained model on patches extracted from testing images. Our training dataset contains 408 normal subjects, including 1961 full-field digital mammography images. Our testing datasets contains 276 subjects. Specifically, 106 of them were patients diagnosed with Ductal Carcinoma In-Situ (DCIS); 70 of them were diagnosed with Invasive Ductal Carcinoma (IDC); the rest 100 are normal cases containing 484 negative screening mammograms. Patches extracted from DCIS and IDC cases (positive patches) contain MC clusters, whereas patches extracted from normal cases (negative patches) don't. As the model is trained only on negative images that do not contain MCs, it cannot reconstruct MCs well, and thus, the reconstruction error will be larger on positive patches than negative patches. Our detection algorithm's decision is made based on Max-Squared Error between autoencoder's input and output patches. To confirm the results were not simply due to blurring, we then compared our designed detector with unsharp mask with Gaussian blur results. The results using the unsupervised autoencoder on testing patches with size 64×64 achieves an AUC result of 0.93. The best performance on testing patches using Gaussian blur with kernel size equal to 11has an overall AUC of 0.82.

Authors
Hou, R; Ren, Y; Grimm, LJ; Mazurowski, MA; Marks, JR; King, L; Maley, CC; Shelley Hwang, E; Lo, JY
MLA Citation
Hou, R., et al. “Malignant microcalcification clusters detection using unsupervised deep autoencoders.” Progress in Biomedical Optics and Imaging  Proceedings of Spie, vol. 10950, 2019. Scopus, doi:10.1117/12.2512829.
Source
scopus
Published In
Progress in Biomedical Optics and Imaging Proceedings of Spie
Volume
10950
Publish Date
2019
DOI
10.1117/12.2512829

Ductal Carcinoma In Situ Management: All or Nothing, or Something in between?

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. Purpose of Review: Standard treatment for ductal carcinoma in situ (DCIS) is similar to that of invasive carcinoma. However, there is significant controversy regarding the true clinical implications of DCIS, and thus, the best management strategy. The aim of this review is to highlight relevant biology, diagnostic considerations, treatment options, and recent clinical trials. Recent Findings: Outcomes are generally excellent with low recurrence rates and exceptional disease-specific survival. Outcomes can be predicted using various prognostic indicators and/or nomograms to guide treatment decisions. Ongoing clinical trials of active surveillance are based upon the argument that ipsilateral invasive recurrence is the most clinically meaningful endpoint. These trials seek to compare ipsilateral invasive cancer diagnoses between standard of care and close monitoring. Summary: Recent trials have revealed the marked heterogeneity in the biology of DCIS, offering an opportunity to de-escalate therapy for women at lowest risk for progression. DCIS also presents an ideal setting in which to test novel prevention agents. Future care of patients with DCIS will include biomarker-based risk assessment in order to better individualize treatment to biologic risk of invasive progression.

Authors
Plichta, JK; Rosenberger, LH; DeChant, CA; Hwang, ES
MLA Citation
Plichta, J. K., et al. “Ductal Carcinoma In Situ Management: All or Nothing, or Something in between?.” Current Breast Cancer Reports, Jan. 2019. Scopus, doi:10.1007/s12609-019-0306-2.
Source
scopus
Published In
Current Breast Cancer Reports
Publish Date
2019
DOI
10.1007/s12609-019-0306-2

Perspectives on Inflammatory Breast Cancer (IBC) Research, Clinical Management and Community Engagement from the Duke IBC Consortium.

Inflammatory breast cancer (IBC) is an understudied and aggressive form of breast cancer with a poor prognosis, accounting for 2-6% of new breast cancer diagnoses but 10% of all breast cancer-related deaths in the United States. Currently there are no therapeutic regimens developed specifically for IBC, and it is critical to recognize that all aspects of treating IBC - including staging, diagnosis, and therapy - are vastly different than other breast cancers. In December 2014, under the umbrella of an interdisciplinary initiative supported by the Duke School of Medicine, researchers, clinicians, research administrators, and patient advocates formed the Duke Consortium for IBC to address the needs of patients in North Carolina (an ethnically and economically diverse state with 100 counties) and across the Southeastern United States. The primary goal of this group is to translate research into action and improve both awareness and patient care through collaborations with local, national and international IBC programs. The consortium held its inaugural meeting on Feb 28, 2018, which also marked Rare Disease Day and convened national research experts, clinicians, patients, advocates, government representatives, foundation leaders, staff, and trainees. The meeting focused on new developments and challenges in the clinical management of IBC, research challenges and opportunities, and an interactive session to garner input from patients, advocates, and community partners that would inform a strategic plan toward continuing improvements in IBC patient care, research, and education.

Authors
Devi, GR; Hough, H; Barrett, N; Cristofanilli, M; Overmoyer, B; Spector, N; Ueno, NT; Woodward, W; Kirkpatrick, J; Vincent, B; Williams, KP; Finley, C; Duff, B; Worthy, V; McCall, S; Hollister, BA; Palmer, G; Force, J; Westbrook, K; Fayanju, O; Suneja, G; Dent, SF; Hwang, ES; Patierno, SR; Marcom, PK
MLA Citation
Devi, Gayathri R., et al. “Perspectives on Inflammatory Breast Cancer (IBC) Research, Clinical Management and Community Engagement from the Duke IBC Consortium..” J Cancer, vol. 10, no. 15, 2019, pp. 3344–51. Pubmed, doi:10.7150/jca.31176.
Website
https://hdl.handle.net/10161/19129
PMID
31293637
Source
pubmed
Published In
Journal of Cancer
Volume
10
Issue
15
Publish Date
2019
Start Page
3344
End Page
3351
DOI
10.7150/jca.31176

Simulation Modeling of Cancer Clinical Trials: Application to Omitting Radiotherapy in Low-risk Breast Cancer.

Background: We used two models to simulate a proposed noninferiority trial of radiotherapy (RT) omission in low-risk invasive breast cancer to illustrate how modeling could be used to predict the trial's outcomes, inform trial design, and contribute to practice debates. Methods: The proposed trial was a prospective randomized trial of no-RT vs RT in women age 40 to 74 years undergoing lumpectomy and endocrine therapy for hormone receptor-positive, human epidermal growth factor receptor 2-negative, stage I breast cancer with an Oncotype DX score of 18 or lower. The primary endpoint was recurrence-free interval (RFI), including locoregional recurrence, distant recurrence, and breast cancer death. Noninferiority required the two-sided 90% confidence interval of the RFI hazard ratio (HR) for no-RT vs RT to be entirely below 1.7. Model inputs included published data. The trial was simulated 1000 times, and results were summarized as percent concluding noninferiority and mean (standard deviation) of hazard ratios for Model GE and Model M, respectively. Results: Noninferiority was demonstrated in 18.0% and 3.7% for the two models. The respective means (SD) of the RFI hazard ratios were 1.8 (0.7) and 2.4 (0.9); most were locoregional recurrences. The mean five-year RFI rates for no-RT vs RT (SD) were 92.7% (2.9%) vs 95.5% (2.2%) and 88.4% (2.0%) vs 94.5% (1.6%). Both models showed little or no difference in breast cancer-specific or overall survival. Alternative definitions of low risk based on combinations of age and grade produced similar results. Conclusions: The proposed trial was unlikely to show noninferiority of omitting radiotherapy even using alternative definitions of low-risk, as the endpoint included local recurrence. Future trials regarding radiotherapy should address absolute reduction in recurrence and impact of type of recurrence on the patient.

Authors
Jayasekera, J; Li, Y; Schechter, CB; Jagsi, R; Song, J; White, J; Luta, G; Chapman, J-AW; Feuer, EJ; Zellars, RC; Stout, N; Julian, TB; Whelan, T; Huang, X; Shelley Hwang, E; Hopkins, JO; Sparano, JA; Anderson, SJ; Fyles, AW; Gray, R; Sauerbrei, W; Mandelblatt, J; Berry, DA; CISNET-BOLD Collaborative Group,
MLA Citation
Jayasekera, Jinani, et al. “Simulation Modeling of Cancer Clinical Trials: Application to Omitting Radiotherapy in Low-risk Breast Cancer..” J Natl Cancer Inst, vol. 110, no. 12, Dec. 2018, pp. 1360–69. Pubmed, doi:10.1093/jnci/djy059.
PMID
29718314
Source
pubmed
Published In
J Natl Cancer Inst
Volume
110
Issue
12
Publish Date
2018
Start Page
1360
End Page
1369
DOI
10.1093/jnci/djy059

Association of Low Nodal Positivity Rate Among Patients With ERBB2-Positive or Triple-Negative Breast Cancer and Breast Pathologic Complete Response to Neoadjuvant Chemotherapy.

Importance: A recent publication reported that of 527 patients with clinically node-negative (cN0) cT1/cT2 triple-negative breast cancer (TNBC) or ERBB2-positive disease treated with neoadjuvant chemotherapy (NAC), 100% of those who achieved a breast pathologic complete response (pCR) had pathologic node negativity (pN0). Eliminating axillary surgery in these patients has been suggested as safe based on these results. Objective: To evaluate nodal positivity rates in patients with cT1/cT2 N0 ERBB2-positive disease and TNBC with a breast pCR after NAC using the National Cancer Database (NCDB), which included academic and community settings. Design, Setting, and Participants: This retrospective study reviewed data from the NCDB from January 1, 2010, through December 31, 2015. Participants included patients with cN0/cN1 cT1/cT2 breast cancer who received NAC followed by surgery. Pathologic nodal positivity rates by breast pCR were compared in cN0 and cN1 disease, within each tumor subtype (ERBB2-positive, TNBC, and hormone receptor-positive/ERBB2-negative). Data were analyzed from September 13, 2017, through January 30, 2018. Exposures: Neoadjuvant chemotherapy followed by surgery. Main Outcomes and Measures: The pathologic nodal positivity rate after NAC (ypN) specifically in patients with cT1/cT2 cN0 ERBB2-positive disease or TNBC who achieve a breast pCR after NAC. Results: A total of 30 821 patients with cT1/cT2 cN0/cN1 breast cancer treated with NAC and surgical resection (99.6% female; mean [SD] age, 52.0 [11.5] years) were identified. Of 6802 patients with cN0 ERBB2-positive disease, 3062 (45.0%) achieved breast pCR and of those, 49 (1.6%; 95% CI, 1.2%-2.1%) were ypN positive. In 6222 patients with cN0 TNBC, 2315 (37.2%) achieved breast pCR, and of those, 36 (1.6%; 95% CI, 1.1%-2.1%) were pathologic node positive after NAC. Rates of ypN positivity were higher in patients with cN0 and residual disease in the breast; 632 of 3740 (16.9%) with ERBB2-positive disease and 492 of 3907 (12.6%) with TNBC with residual disease in the breast were node positive (P < .001). Among 4164 patients with cN1 ERBB2-positive disease, 1801 (43.3%) achieved breast pCR, with 223 of those (12.4%) being ypN positive. In 3293 patients with TNBC, 1229 (37.3%) achieved breast pCR, with 173 of these (14.1%) being ypN postive. Breast pCR rates were lower in hormone receptor-positive/ERBB2-negative disease (646 of 5069 [12.7%] for cN0; 711 of 5271 [13.5%] for cN1) and ypN positivity rates were 26 of 646 (4.0%) in cN0 vs 217 of 711 (30.5%) in cN1 disease with breast pCR and 1464 of 4423 (33.1%) in cN0 disease vs 3775 of 4560 (82.8%) in cN1 disease with residual disease in the breast. Conclusions and Relevance: In this study, the highest rates of breast pCR were seen in ERBB2-positive disease and TNBC. In patients with cN0 ERBB2-positive disease or TNBC with breast pCR, the nodal positivity rate was less than 2%, which supports consideration of omission of axillary surgery in this subset of patients.

Authors
Barron, AU; Hoskin, TL; Day, CN; Hwang, ES; Kuerer, HM; Boughey, JC
MLA Citation
Barron, Alison U., et al. “Association of Low Nodal Positivity Rate Among Patients With ERBB2-Positive or Triple-Negative Breast Cancer and Breast Pathologic Complete Response to Neoadjuvant Chemotherapy..” Jama Surg, vol. 153, no. 12, Dec. 2018, pp. 1120–26. Pubmed, doi:10.1001/jamasurg.2018.2696.
PMID
30193375
Source
pubmed
Published In
Jama Surg
Volume
153
Issue
12
Publish Date
2018
Start Page
1120
End Page
1126
DOI
10.1001/jamasurg.2018.2696

Financial Burden Related to Decisions for Breast Cancer Surgery

Authors
Greenup, RA; Rushing, C; Fish, L; Campbell, BM; Tolnitch, L; Hyslop, T; Peppercorn, J; Wheeler, S; Zafar, Y; Myers, ER; Hwang, ES
MLA Citation
Greenup, Rachel A., et al. “Financial Burden Related to Decisions for Breast Cancer Surgery.” Journal of Womens Health, vol. 27, no. 11, MARY ANN LIEBERT, INC, 2018, pp. 1422–23.
Source
wos
Published In
Journal of Women'S Health (2002)
Volume
27
Issue
11
Publish Date
2018
Start Page
1422
End Page
1423

Intra-tumor molecular heterogeneity in breast cancer: definitions of measures and association with distant recurrence-free survival.

PURPOSE: The purpose of the study was to define quantitative measures of intra-tumor heterogeneity in breast cancer based on histopathology data gathered from multiple samples on individual patients and determine their association with distant recurrence-free survival (DRFS). METHODS: We collected data from 971 invasive breast cancers, from 1st January 2000 to 23rd March 2014, that underwent repeat tumor sampling at our institution. We defined and calculated 31 measures of intra-tumor heterogeneity including ER, PR, and HER2 immunohistochemistry (IHC), proliferation, EGFR IHC, grade, and histology. For each heterogeneity measure, Cox proportional hazards models were used to determine whether patients with heterogeneous disease had different distant recurrence-free survival (DRFS) than those with homogeneous disease. RESULTS: The presence of heterogeneity in ER percentage staining was prognostic of reduced DRFS with a hazard ratio of 4.26 (95% CI 2.22-8.18, p < 0.00002). It remained significant after controlling for the ER status itself (p < 0.00062) and for patients that had chemotherapy (p < 0.00032). Most of the heterogeneity measures did not show any association with DRFS despite the considerable sample size. CONCLUSIONS: Intra-tumor heterogeneity of ER receptor status may be a predictor of patient DRFS. Histopathologic data from multiple tissue samples may offer a view of tumor heterogeneity and assess recurrence risk.

Authors
Saha, A; Harowicz, MR; Cain, EH; Hall, AH; Hwang, E-SS; Marks, JR; Marcom, PK; Mazurowski, MA
MLA Citation
Saha, Ashirbani, et al. “Intra-tumor molecular heterogeneity in breast cancer: definitions of measures and association with distant recurrence-free survival..” Breast Cancer Res Treat, vol. 172, no. 1, Nov. 2018, pp. 123–32. Pubmed, doi:10.1007/s10549-018-4879-7.
PMID
29992418
Source
pubmed
Published In
Breast Cancer Res Treat
Volume
172
Issue
1
Publish Date
2018
Start Page
123
End Page
132
DOI
10.1007/s10549-018-4879-7

Implications for Breast Cancer Restaging Based on the 8th Edition AJCC Staging Manual.

OBJECTIVE:: We assessed the changes that have resulted from the latest breast cancer staging guidelines and the potential impact on prognosis. BACKGROUND: Contemporary data suggest that combining anatomic staging and tumor biology yields a predictive synergy for determining breast cancer prognosis. This forms the basis for the American Joint Committee on Cancer's (AJCC) Staging Manual, 8th edition. We assessed the changes that have resulted from the new staging guidelines and the potential impact on prognosis. METHODS: Women with stages I to III breast cancer from 2010 to 2014 in the National Cancer Data Base were pathologically staged according to the 7th and 8th editions of the AJCC Staging Manual. Patient characteristics and restaging outcomes were summarized. Unadjusted overall survival (OS) was estimated, and differences were assessed. Cox proportional-hazards models were utilized to estimate the adjusted association of stage with OS. RESULTS: After restaging the 493,854 women identified, 6.8% were upstaged and 29.7% were downstaged. The stage changes varied by tumor histology, receptor status, tumor grade, and Oncotype DX scores (all P < 0.0001). Applying the 8th edition criteria yielded an incremental reduction in survival for each increase in stage, which was not consistently seen in the 7th edition. In a subgroup analysis based on hormone receptor (HR) status, those with stages II and III, and HR- disease had a worse OS than those with HR+ disease. CONCLUSIONS: Applying the 8th edition staging criteria resulted in a stage change for >35% of patients diagnosed with invasive breast cancer and refined OS estimates. Overall, the transition to the 8th edition is expected to better drive clinical care, treatment recommendations, and future research.

Authors
Plichta, JK; Ren, Y; Thomas, SM; Greenup, RA; Fayanju, OM; Rosenberger, LH; Hyslop, T; Hwang, ES
MLA Citation
Plichta, Jennifer K., et al. “Implications for Breast Cancer Restaging Based on the 8th Edition AJCC Staging Manual..” Ann Surg, Oct. 2018. Pubmed, doi:10.1097/SLA.0000000000003071.
PMID
30312199
Source
pubmed
Published In
Ann Surg
Publish Date
2018
DOI
10.1097/SLA.0000000000003071

Axillary Nodal Evaluation in Elderly Breast Cancer Patients: Potential Effects on Treatment Decisions and Survival.

BACKGROUND: Recent studies suggest that surgical lymph node (LN) evaluation may be omitted in select elderly breast cancer patients as it may not influence adjuvant therapy decisions. To evaluate differences in adjuvant therapy receipt and overall survival (OS), we compared clinically node-negative (cN0) elderly patients who did and did not undergo axillary surgery. METHODS: Patients aged ≥70 years in the National Cancer Database (2004-2014) with cT1-3, cN0 breast cancer were divided into two cohorts-those with surgical LN evaluation (one or more nodes removed) and those without (no nodes removed). Propensity scores were used to match patients based on age, year of diagnosis, tumor grade, cT stage, estrogen receptor status, and Charlson-Deyo comorbidity score. A Cox proportional hazards model was used to estimate the effect of LN surgery on OS. RESULTS: Overall, 133,778 patients were matched, of whom 102,247 patients (76.4%) underwent nodal surgery. Patients undergoing nodal surgery were more likely to receive chemotherapy (pN1-3: 22.2%; pN0: 5.8%; cN0-no nodal surgery: 2.8%; p < 0.001), radiation (pN1-3: 49.7%; pN0: 47.5%; cN0-no nodal surgery: 26%; p < 0.001), and endocrine therapy (pN1-3: 72%; pN0: 58.5%; cN0-no nodal surgery: 46.5%; p < 0.001). After adjustment for known covariates, patients who did not undergo nodal surgery had a worse OS (hazard ratio 1.66, 95% confidence interval 1.61-1.70). CONCLUSIONS: For elderly cN0 breast cancer patients, axillary surgery was associated with higher rates of adjuvant therapy and improved OS. A selective approach to omitting nodal surgery should be considered in elderly patients with cN0 breast cancer as axillary staging may influence subsequent treatment decisions and long-term outcomes.

Authors
Tamirisa, N; Thomas, SM; Fayanju, OM; Greenup, RA; Rosenberger, LH; Hyslop, T; Hwang, ES; Plichta, JK
MLA Citation
Tamirisa, Nina, et al. “Axillary Nodal Evaluation in Elderly Breast Cancer Patients: Potential Effects on Treatment Decisions and Survival..” Ann Surg Oncol, vol. 25, no. 10, 2018, pp. 2890–98. Pubmed, doi:10.1245/s10434-018-6595-2.
PMID
29968029
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
25
Issue
10
Publish Date
2018
Start Page
2890
End Page
2898
DOI
10.1245/s10434-018-6595-2

The Association of Extent of Axillary Surgery and Survival in Women with N2-3 Invasive Breast Cancer.

BACKGROUND: Although surgical management of the axilla for breast cancer continues to evolve, axillary lymphadenectomy remains the standard of care for women with advanced nodal disease. We sought to evaluate national patterns of care in axillary surgery, and its association with overall survival (OS) among women with N2-3 invasive breast cancer. METHODS: Women (18-90 years) with clinical N2-3 invasive breast cancer who underwent axillary surgery were identified from the National Cancer Data Base (NCDB) from 2004 to 2013. Axillary surgery was categorized as sentinel lymph node biopsy (SLNB, 1-5 nodes) or axillary lymph node dissection (ALND, ≥ 10 nodes). Patient and treatment characteristics, trends over time, and overall survival (OS) were compared by surgical treatment. RESULTS: Overall, 22,156 patients were identified. At diagnosis, 68.5% had cN2 and 31.5% had cN3 disease. Treatment included: lumpectomy (27%), mastectomy (73%), adjuvant chemotherapy (53.4%), neoadjuvant chemotherapy (NAC) (39.7%), radiation (74%), and endocrine therapy (54.4%). In total, 9.9% (n = 2190) underwent SLNB and 90.1% (n = 19,966) underwent ALND. Receipt of SLNB was associated with private insurance, grade 3 disease, invasive ductal cancer, NAC, and lumpectomy (all p < 0.001). After adjustment for known covariates, including chemotherapy use, ALND was associated with improved survival [hazard ratio (HR) 0.68, p < 0.001] and this effect was similar for N2 and N3 patients (axillary surgery × cN-stage interaction p = 0.29). CONCLUSIONS: Axillary lymphadenectomy was associated with improved survival in patients presenting with clinical N2-3 invasive breast cancer. Further studies, particularly in the neoadjuvant setting, are needed to identify breast cancer patients with advanced nodal disease who may safely avoid a lesser extent of axillary surgery.

Authors
Park, TS; Thomas, SM; Rosenberger, LH; Fayanju, OM; Plichta, JK; Blitzblau, RC; Ong, CT; Hyslop, T; Hwang, ES; Greenup, RA
MLA Citation
Park, Tristen S., et al. “The Association of Extent of Axillary Surgery and Survival in Women with N2-3 Invasive Breast Cancer..” Ann Surg Oncol, vol. 25, no. 10, Oct. 2018, pp. 3019–29. Pubmed, doi:10.1245/s10434-018-6587-2.
PMID
29978365
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
25
Issue
10
Publish Date
2018
Start Page
3019
End Page
3029
DOI
10.1245/s10434-018-6587-2

The Changing Paradigms for Breast Cancer Surgery: Performing Fewer and Less-Invasive Operations.

Historically, through the conduct of prospective clinical trials, breast cancer surgeons have performed less radical breast and axillary surgeries with no survival decrement to our patients. Currently, other opportunities exist for the treating breast surgeon to do less. Possibilities include active surveillance for ductal carcinoma in situ, ablative therapy for small primary breast cancers, selective omission of a sentinel node biopsy, and selective elimination of breast surgery after neoadjuvant systemic therapy. Breast surgeons must be leaders in the development and testing of effective therapy with the least intervention possible.

Authors
Ollila, DW; Hwang, ES; Brenin, DR; Kuerer, HM; Yao, K; Feldman, S
MLA Citation
Ollila, David W., et al. “The Changing Paradigms for Breast Cancer Surgery: Performing Fewer and Less-Invasive Operations..” Ann Surg Oncol, vol. 25, no. 10, Oct. 2018, pp. 2807–12. Pubmed, doi:10.1245/s10434-018-6618-z.
PMID
29968033
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
25
Issue
10
Publish Date
2018
Start Page
2807
End Page
2812
DOI
10.1245/s10434-018-6618-z

The Clinical Significance of Breast-only and Node-only Pathologic Complete Response (pCR) After Neoadjuvant Chemotherapy (NACT): A Review of 20,000 Breast Cancer Patients in the National Cancer Data Base (NCDB).

OBJECTIVE: To determine whether the association between overall survival (OS) and response to neoadjuvant chemotherapy (NACT) in breast cancer patients varies with tumor subtype and anatomic extent of pathologic complete response (pCR). BACKGROUND: pCR after NACT predicts improved OS in breast cancer, but it is unclear whether pCR limited to the breast or axilla is also associated with OS. METHODS: Women with cT1-3/cN0-1 breast cancer diagnosed in 2010 to 2014 who underwent surgery following NACT were identified in the NCDB and divided into 4 subtypes based on reported hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. Kaplan-Meier curves and Cox proportional hazards models were used to estimate OS. Multivariate logistic regression was used to identify factors associated with post-NACT response, defined as upstage (yp stage>clinical stage); no change (clinical stage = yp stage); overall (breast+axilla, ypT0N0), breast-only (ypT0N1/N1mic), or node-only (ypT1-3N0) pCR. RESULTS: Of 33,162 identified patients, 20,265 experienced overall pCR (n = 6370, 19.2%), breast-only pCR (n = 494, 1.5%), node-only pCR (n = 1133, 3.4%), no stage change (n = 9641, 29.1%), or upstage (n = 2627, 7.9%). Compared with no stage change, breast-only pCR was associated with improved OS in triple-negative disease [hazard ratio = 0.58, 95% confidence interval (95% CI) = 0.37-0.89], and node-only pCR was associated with improved OS in both triple-negative (hazard ratio = 0.55,95% CI = 0.39-0.76) and HR+/HER2- disease (hazard ratio = 0.54, 95% CI = 0.33-0.89). For patients achieving overall (breast+axilla) pCR, unadjusted 5-year OS was 0.94 (95% CI = 0.93-0.95), with no difference between patients who were cN0 (hazard ratio = 0.95, 95% CI = 0.93-0.96) or cN1 (hazard ratio = 0.94, 95% CI = 0.92-0.96) at diagnosis. CONCLUSIONS: In node-positive patients, pCR limited to either the breast or axilla predicts survival for select receptor subtypes. In patients achieving pCR in both the breast and axilla, survival is driven by response to NACT rather than presenting cN stage.

Authors
Fayanju, OM; Ren, Y; Thomas, SM; Greenup, RA; Plichta, JK; Rosenberger, LH; Tamirisa, N; Force, J; Boughey, JC; Hyslop, T; Hwang, ES
MLA Citation
Fayanju, Oluwadamilola M., et al. “The Clinical Significance of Breast-only and Node-only Pathologic Complete Response (pCR) After Neoadjuvant Chemotherapy (NACT): A Review of 20,000 Breast Cancer Patients in the National Cancer Data Base (NCDB)..” Ann Surg, vol. 268, no. 4, Oct. 2018, pp. 591–601. Pubmed, doi:10.1097/SLA.0000000000002953.
PMID
30048319
Source
pubmed
Published In
Ann Surg
Volume
268
Issue
4
Publish Date
2018
Start Page
591
End Page
601
DOI
10.1097/SLA.0000000000002953

Metaplastic Breast Cancer Treatment and Outcomes in 2500 Patients: A Retrospective Analysis of a National Oncology Database.

BACKGROUND: Metaplastic breast cancer (MBC) is characterized by chemoresistance and hematogenous spread. We sought to identify factors associated with improved MBC outcomes and increased likelihood of MBC diagnosis. METHODS: Women ≥ 18 years of age with stage I-III MBC and non-MBC diagnosed between 2010 and 2014 were identified in the National Cancer Data Base. Kaplan-Meier and multivariate Cox proportional hazards models were used to estimate associations with overall survival (OS). Multivariate logistic regression identified factors associated with MBC diagnosis. RESULTS: Overall, 2451 MBC and 568,057 non-MBC patients were included; 70.3% of MBC vs. 11.3% of non-MBC patients were triple negative (p < 0.001). Five-year OS was reduced among MBC vs. non-MBC patients for the entire cohort (72.7 vs. 87.5%) and among triple-negative patients (71.1 vs. 77.8%; both p < 0.001). In MBC, triple-negative (vs. luminal) subtype was not associated with worse OS (hazard ratio [HR] 1.16, 95% confidence interval [CI] 0.88-1.54, p = 0.28). Compared with non-MBC patients, MBC patients were more likely to receive mastectomy (59.0 vs. 44.9%), chemotherapy (74.1 vs. 43.1%), and axillary lymph node dissection (ALND; 35.2 vs. 32.2%, all p ≤ 0.001). MBC patients more frequently had negative ALND (pN0) than non-MBC patients (20.0 vs. 10.6%, p < 0.001). Among MBC patients, chemotherapy (HR 0.69, 95% CI 0.53-0.89, p = 0.004) and radiotherapy (HR 0.52, 95% CI 0.39-0.69, p < 0.001) were associated with improved survival, while ALND was associated with decreased survival (HR 1.37, 95% CI 1.06-1.77, p = 0.02). CONCLUSIONS: MBC patients had worse survival than non-MBC patients, independent of receptor status, suggesting that MBC may confer an additional survival disadvantage. Multimodal therapy was associated with improved outcomes, but ALND was not and may be overutilized in MBC.

Authors
Ong, CT; Campbell, BM; Thomas, SM; Greenup, RA; Plichta, JK; Rosenberger, LH; Force, J; Hall, A; Hyslop, T; Hwang, ES; Fayanju, OM
MLA Citation
Ong, Cecilia T., et al. “Metaplastic Breast Cancer Treatment and Outcomes in 2500 Patients: A Retrospective Analysis of a National Oncology Database..” Ann Surg Oncol, vol. 25, no. 8, Aug. 2018, pp. 2249–60. Pubmed, doi:10.1245/s10434-018-6533-3.
PMID
29855830
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
25
Issue
8
Publish Date
2018
Start Page
2249
End Page
2260
DOI
10.1245/s10434-018-6533-3

Extent of axillary surgery in women with Stage IV breast cancer

Authors
Lane, W; Thomas, S; Plichta, J; Rosenberger, L; Fayanju, O; Hyslop, T; Hwang, ES; Greenup, R
MLA Citation
Lane, Whitney, et al. “Extent of axillary surgery in women with Stage IV breast cancer.” Annals of Surgical Oncology, vol. 25, SPRINGER, 2018, pp. 291–92.
Source
wos
Published In
Annals of Surgical Oncology
Volume
25
Publish Date
2018
Start Page
291
End Page
292

Pediatric phyllodes tumors: A review of the National Cancer Data Base and adherence to NCCN guidelines for phyllodes tumor treatment.

BACKGROUND: Phyllodes tumors are fibroepithelial breast lesions that are uncommon in women and rare among children. Due to scarcity, few large pediatric phyllodes tumor series exist. Current guidelines do not differentiate treatment recommendations between children and adults. We examined national guideline adherence for children and adults. METHODS: We queried the NCDB (2004-2014) for female patients with phyllodes tumor histology, excluding patients with missing age or survival data. Patients were stratified by age (pediatric <21, adult ≥21), and compared based on patient characteristics, treatment patterns, and survival. RESULTS: We identified 2787 cases of phyllodes tumor (2725 adult, 62 pediatric). Median age was 17years in children and 52years in adults. Margin positivity rates and median tumor size were similar between adults and children. Treatment was discordant with NCCN guidelines in 28.6% of adults and 14.5% of children through use of axillary staging, chemotherapy, adjuvant endocrine therapy, and radiotherapy. Five-year and ten-year survival were comparable between both groups. CONCLUSION: Children and adults present with similarly sized phyllodes tumors. Trends reveal high margin positivity rates, and overtreatment with regional axillary staging and systemic adjuvant therapies. Particularly in children, treatment decisions must consider risks of adjuvant therapy including radiation-related second primary cancers, given uncertain benefit. TYPE OF STUDY: Retrospective Comparative Study. LEVEL OF EVIDENCE: Level III.

Authors
Leraas, HJ; Rosenberger, LH; Ren, Y; Ezekian, B; Nag, UP; Reed, CR; Thomas, SM; Hwang, E-SS; Tracy, ET
MLA Citation
Leraas, Harold J., et al. “Pediatric phyllodes tumors: A review of the National Cancer Data Base and adherence to NCCN guidelines for phyllodes tumor treatment..” J Pediatr Surg, vol. 53, no. 6, June 2018, pp. 1123–28. Pubmed, doi:10.1016/j.jpedsurg.2018.02.070.
PMID
29605260
Source
pubmed
Published In
J Pediatr Surg
Volume
53
Issue
6
Publish Date
2018
Start Page
1123
End Page
1128
DOI
10.1016/j.jpedsurg.2018.02.070

Patient Preferences for Health States Following Alternative Management Options for Ductal Carcinoma in Situ

Authors
Campbell, BM; Yang, J; Gonzalez, JM; Reed, SD; Havrilesky, L; Johnson, FR; Hwang, ES
MLA Citation
Campbell, B. M., et al. “Patient Preferences for Health States Following Alternative Management Options for Ductal Carcinoma in Situ.” Value in Health, vol. 21, Elsevier BV, 2018, pp. S11–12. Crossref, doi:10.1016/j.jval.2018.04.056.
Source
crossref
Published In
Value in Health
Volume
21
Publish Date
2018
Start Page
S11
End Page
S12
DOI
10.1016/j.jval.2018.04.056

Prediction of Occult Invasive Disease in Ductal Carcinoma in Situ Using Deep Learning Features.

PURPOSE: The aim of this study was to determine whether deep features extracted from digital mammograms using a pretrained deep convolutional neural network are prognostic of occult invasive disease for patients with ductal carcinoma in situ (DCIS) on core needle biopsy. METHODS: In this retrospective study, digital mammographic magnification views were collected for 99 subjects with DCIS at biopsy, 25 of which were subsequently upstaged to invasive cancer. A deep convolutional neural network model that was pretrained on nonmedical images (eg, animals, plants, instruments) was used as the feature extractor. Through a statistical pooling strategy, deep features were extracted at different levels of convolutional layers from the lesion areas, without sacrificing the original resolution or distorting the underlying topology. A multivariate classifier was then trained to predict which tumors contain occult invasive disease. This was compared with the performance of traditional "handcrafted" computer vision (CV) features previously developed specifically to assess mammographic calcifications. The generalization performance was assessed using Monte Carlo cross-validation and receiver operating characteristic curve analysis. RESULTS: Deep features were able to distinguish DCIS with occult invasion from pure DCIS, with an area under the receiver operating characteristic curve of 0.70 (95% confidence interval, 0.68-0.73). This performance was comparable with the handcrafted CV features (area under the curve = 0.68; 95% confidence interval, 0.66-0.71) that were designed with prior domain knowledge. CONCLUSIONS: Despite being pretrained on only nonmedical images, the deep features extracted from digital mammograms demonstrated comparable performance with handcrafted CV features for the challenging task of predicting DCIS upstaging.

Authors
Shi, B; Grimm, LJ; Mazurowski, MA; Baker, JA; Marks, JR; King, LM; Maley, CC; Hwang, ES; Lo, JY
MLA Citation
Shi, Bibo, et al. “Prediction of Occult Invasive Disease in Ductal Carcinoma in Situ Using Deep Learning Features..” J Am Coll Radiol, vol. 15, no. 3 Pt B, Mar. 2018, pp. 527–34. Pubmed, doi:10.1016/j.jacr.2017.11.036.
PMID
29398498
Source
pubmed
Published In
Journal of the American College of Radiology : Jacr
Volume
15
Issue
3 Pt B
Publish Date
2018
Start Page
527
End Page
534
DOI
10.1016/j.jacr.2017.11.036

Trends and variations in postmastectomy radiation therapy for breast cancer in patients with 1 to 3 positive lymph nodes: A National Cancer Data Base analysis.

BACKGROUND: High-level evidence is lacking to guide treatment decisions about postmastectomy radiation therapy (PMRT) in patients who have breast cancer with 1 to 3 positive lymph nodes who receive contemporary systemic therapies, leading to potential variations in PMRT delivery. The objective of this study was to examine nationwide trends in PMRT use in this group. METHODS: The National Cancer Data Base (NCDB) was used to identify 93,372 women who had T1-T2N1 breast cancer diagnosed between 2003 and 2012. Patients who received neoadjuvant chemotherapy or radiation therapy (RT) and those who had bilateral breast cancers were excluded. Time trends were evaluated using the Cochrane-Armitage test and correlated the receipt of PMRT with various patient demographic, facility, clinicopathologic, and treatment variables using multivariable logistic regression. A second analysis was performed for patients who were diagnosed during 2010 and included radiation oncologist density as an additional covariate. P values < .0001 were considered statistically significant. RESULTS: Overall, 22.5% of the study population received PMRT, representing an increase from 19.1% in 2003 to 30.3% in 2012. Factors associated with greater PMRT use included younger age, lower Charlson-Deyo comorbidity scores, shorter distance to the treating facility, treatment at a comprehensive cancer program, facility location in the New England Census division, and higher density of radiation oncologists. Increased PMRT use was associated with later year of diagnosis, receipt of chemotherapy, receipt of hormone therapy, higher grade disease, larger tumor size, greater numbers of positive lymph nodes, positive margins, and absence of immediate breast reconstruction (all P < .0001). CONCLUSIONS: The receipt of PMRT by patients with breast cancer who have 1 to 3 positive lymph nodes has increased over time, with wide variability in practice patterns in the United States. Cancer 2018;124:482-90. © 2017 American Cancer Society.

Authors
Ohri, N; Sittig, MP; Tsai, CJ; Hwang, E-SS; Mittendorf, EA; Shi, W; Zhang, Z; Ho, AY
MLA Citation
Ohri, Nisha, et al. “Trends and variations in postmastectomy radiation therapy for breast cancer in patients with 1 to 3 positive lymph nodes: A National Cancer Data Base analysis..” Cancer, vol. 124, no. 3, Feb. 2018, pp. 482–90. Pubmed, doi:10.1002/cncr.31080.
PMID
29112227
Source
pubmed
Published In
Cancer
Volume
124
Issue
3
Publish Date
2018
Start Page
482
End Page
490
DOI
10.1002/cncr.31080

Is it cancer or not? A qualitative exploration of patient perspectives surrounding the diagnosis and treatment of DCIS

Authors
Rosenberg, SM; Gierisch, JM; Lowenstein, C; Frank, ES; Collyer, D; Partridge, AH; Hwang, ES
MLA Citation
Rosenberg, Shoshana M., et al. “Is it cancer or not? A qualitative exploration of patient perspectives surrounding the diagnosis and treatment of DCIS.” Cancer Research, vol. 78, no. 4, AMER ASSOC CANCER RESEARCH, 2018.
Source
wos
Published In
Cancer Research
Volume
78
Issue
4
Publish Date
2018

Quantifying the natural history and overtreatment rate of ductal carcinoma in situ

Authors
Ryser, MD; Weaver, DL; Marks, JR; Hyslop, T; Hwang, ES
MLA Citation
Ryser, Marc D., et al. “Quantifying the natural history and overtreatment rate of ductal carcinoma in situ.” Cancer Research, vol. 78, no. 4, AMER ASSOC CANCER RESEARCH, 2018.
Source
wos
Published In
Cancer Research
Volume
78
Issue
4
Publish Date
2018

Primary endocrine therapy for ER-positive ductal carcinoma in situ (DCIS) CALGB 40903 (Alliance)

Authors
Hwang, ES; Duong, S; Bedrosian, I; Allred, J; Wisner, D; Hyslop, T; Caudle, A; Guenther, J; Hudis, C; Winer, E; Esserman, L; Hylton, N
MLA Citation
Hwang, E. Shelley, et al. “Primary endocrine therapy for ER-positive ductal carcinoma in situ (DCIS) CALGB 40903 (Alliance).” Cancer Research, vol. 78, no. 4, AMER ASSOC CANCER RESEARCH, 2018.
Source
wos
Published In
Cancer Research
Volume
78
Issue
4
Publish Date
2018

Treatment Patterns and Outcomes for Breast Cancer with Isolated Supraclavicular Metastases

Authors
Thomas, SM; Fayanju, OM; Plichta, JK; Rosenberger, LH; Force, J; Hyslop, T; Hwang, ES; Greenup, RA
MLA Citation
Thomas, S. M., et al. “Treatment Patterns and Outcomes for Breast Cancer with Isolated Supraclavicular Metastases.” Annals of Surgical Oncology, vol. 25, SPRINGER, 2018, pp. S26–S26.
Source
wos
Published In
Annals of Surgical Oncology
Volume
25
Publish Date
2018
Start Page
S26
End Page
S26

Clinical and Pathologic Stage Discordance is Associated with Breast Cancer Prognosis

Authors
Plichta, JK; Thomas, SM; Greenup, RA; Fayanju, OM; Rosenberger, LH; Tamirisa, N; Hyslop, T; Hwang, ES
MLA Citation
Plichta, J. K., et al. “Clinical and Pathologic Stage Discordance is Associated with Breast Cancer Prognosis.” Annals of Surgical Oncology, vol. 25, SPRINGER, 2018, pp. S94–S94.
Source
wos
Published In
Annals of Surgical Oncology
Volume
25
Publish Date
2018
Start Page
S94
End Page
S94

Breast Cancer Treatment Costs: Surgical Decisions and Preferences for Transparency

Authors
Greenup, RA; Rushing, CN; Fish, LJ; Campbell, B; Hyslop, T; Peppercorn, JM; Myers, ER; Zafar, Y; Hwang, ES
MLA Citation
Greenup, R. A., et al. “Breast Cancer Treatment Costs: Surgical Decisions and Preferences for Transparency.” Annals of Surgical Oncology, vol. 25, SPRINGER, 2018, pp. S15–S15.
Source
wos
Published In
Annals of Surgical Oncology
Volume
25
Publish Date
2018
Start Page
S15
End Page
S15

Race, Marital Status and Stage are Associated with Patient-Reported Distress After Breast Cancer Diagnosis: A Review of > 5000 Patient Visits

Authors
Fayanju, OM; Yenokyan, K; Goldstein, BA; Stashko, I; Power, S; Hwang, ES
MLA Citation
Fayanju, O. M., et al. “Race, Marital Status and Stage are Associated with Patient-Reported Distress After Breast Cancer Diagnosis: A Review of > 5000 Patient Visits.” Annals of Surgical Oncology, vol. 25, SPRINGER, 2018, pp. S54–S54.
Source
wos
Published In
Annals of Surgical Oncology
Volume
25
Publish Date
2018
Start Page
S54
End Page
S54

The Effect of Hospital Volume on Breast Cancer Mortality.

OBJECTIVE: The aim of this study was to determine whether hospital volume was associated with mortality in breast cancer, and what thresholds of case volume impacted survival. BACKGROUND: Prior literature has demonstrated improved survival with treatment at high volume centers among less common cancers requiring technically complex surgery. METHODS: All adults (18 to 90 years) with stages 0-III unilateral breast cancer diagnosed from 2004 to 2012 were identified from the American College of Surgeons National Cancer Data Base (NCDB). A multivariable Cox proportional hazards model with restricted cubic splines was used to examine the association of annual hospital volume and overall survival, after adjusting for measured covariates. Intergroup comparisons of patient and treatment characteristics were conducted with X and analysis of variance (ANOVA). The log-rank test was used to test survival differences between groups. A multivariable Cox proportional hazards model was used to estimate hazard ratios (HRs) associated with each volume group. RESULTS: One million sixty-four thousand two hundred and fifty-one patients met inclusion criteria. The median age of the sample was 60 (interquartile range 50 to 70). Hospitals were categorized into 3 groups using restricted cubic spline analysis: low-volume (<148 cases/year), moderate-volume (148 to 298 cases/year), and high-volume (>298 cases/year). Treatment at high volume centers was associated with an 11% reduction in overall mortality for all patients (HR 0.89); those with stage 0-I, ER+/PR+ or ER+/PR- breast cancers derived the greatest benefit. CONCLUSIONS: Treatment at high volume centers is associated with improved survival for breast cancer patients regardless of stage. High case volume could serve as a proxy for the institutional infrastructure required to deliver complex multidisciplinary breast cancer treatment.

Authors
Greenup, RA; Obeng-Gyasi, S; Thomas, S; Houck, K; Lane, WO; Blitzblau, RC; Hyslop, T; Hwang, ES
MLA Citation
Greenup, Rachel A., et al. “The Effect of Hospital Volume on Breast Cancer Mortality..” Ann Surg, vol. 267, no. 2, Feb. 2018, pp. 375–81. Pubmed, doi:10.1097/SLA.0000000000002095.
PMID
27893532
Source
pubmed
Published In
Ann Surg
Volume
267
Issue
2
Publish Date
2018
Start Page
375
End Page
381
DOI
10.1097/SLA.0000000000002095

How Low Can We Go-and Should We? Risk Reduction for Minimal-Volume DCIS.

Authors
Ryser, MD; Horton, JK; Hwang, ES
MLA Citation
Ryser, Marc D., et al. “How Low Can We Go-and Should We? Risk Reduction for Minimal-Volume DCIS..” Ann Surg Oncol, vol. 25, no. 2, Feb. 2018, pp. 354–55. Pubmed, doi:10.1245/s10434-017-6128-4.
PMID
29134379
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
25
Issue
2
Publish Date
2018
Start Page
354
End Page
355
DOI
10.1245/s10434-017-6128-4

Learning better deep features for the prediction of occult invasive disease in ductal carcinoma in situ through transfer learning

© 2018 SPIE. Purpose: To determine whether domain transfer learning can improve the performance of deep features extracted from digital mammograms using a pre-trained deep convolutional neural network (CNN) in the prediction of occult invasive disease for patients with ductal carcinoma in situ (DCIS) on core needle biopsy. Method: In this study, we collected digital mammography magnification views for 140 patients with DCIS at biopsy, 35 of which were subsequently upstaged to invasive cancer. We utilized a deep CNN model that was pre-trained on two natural image data sets (ImageNet and DTD) and one mammographic data set (INbreast) as the feature extractor, hypothesizing that these data sets are increasingly more similar to our target task and will lead to better representations of deep features to describe DCIS lesions. Through a statistical pooling strategy, three sets of deep features were extracted using the CNNs at different levels of convolutional layers from the lesion areas. A logistic regression classifier was then trained to predict which tumors contain occult invasive disease. The generalization performance was assessed and compared using repeated random sub-sampling validation and receiver operating characteristic (ROC) curve analysis. Result: The best performance of deep features was from CNN model pre-trained on INbreast, and the proposed classifier using this set of deep features was able to achieve a median classification performance of ROC-AUC equal to 0.75, which is significantly better (p<=0.05) than the performance of deep features extracted using ImageNet data set (ROCAUC = 0.68). Conclusion: Transfer learning is helpful for learning a better representation of deep features, and improves the prediction of occult invasive disease in DCIS.

Authors
Shi, B; Hou, R; Mazurowski, MA; Grimm, LJ; Ren, Y; Marks, JR; King, LM; Maley, CC; Hwang, ES; Lo, JY
MLA Citation
Shi, B., et al. “Learning better deep features for the prediction of occult invasive disease in ductal carcinoma in situ through transfer learning.” Progress in Biomedical Optics and Imaging  Proceedings of Spie, vol. 10575, 2018. Scopus, doi:10.1117/12.2293594.
Source
scopus
Published In
Progress in Biomedical Optics and Imaging Proceedings of Spie
Volume
10575
Publish Date
2018
DOI
10.1117/12.2293594

Deep learning-based features of breast MRI for prediction of occult invasive disease following a diagnosis of ductal carcinoma in situ: Preliminary data

© 2018 SPIE. Approximately 25% of patients with ductal carcinoma in situ (DCIS) diagnosed from core needle biopsy are subsequently upstaged to invasive cancer at surgical excision. Identifying patients with occult invasive disease is important as it changes treatment and precludes enrollment in active surveillance for DCIS. In this study, we investigated upstaging of DCIS to invasive disease using deep features. While deep neural networks require large amounts of training data, the available data to predict DCIS upstaging is sparse and thus directly training a neural network is unlikely to be successful. In this work, a pre-trained neural network is used as a feature extractor and a support vector machine (SVM) is trained on the extracted features. We used the dynamic contrast-enhanced (DCE) MRIs of patients at our institution from January 1, 2000, through March 23, 2014 who underwent MRI following a diagnosis of DCIS. Among the 131 DCIS patients, there were 35 patients who were upstaged to invasive cancer. Area under the ROC curve within the 10-fold cross-validation scheme was used for validation of our predictive model. The use of deep features was able to achieve an AUC of 0.68 (95% CI: 0.56-0.78) to predict occult invasive disease. This preliminary work demonstrates the promise of deep features to predict surgical upstaging following a diagnosis of DCIS.

Authors
Zhu, Z; Harowicz, M; Zhang, J; Saha, A; Grimm, LJ; Hwang, S; Mazurowski, MA
MLA Citation
Zhu, Z., et al. “Deep learning-based features of breast MRI for prediction of occult invasive disease following a diagnosis of ductal carcinoma in situ: Preliminary data.” Progress in Biomedical Optics and Imaging  Proceedings of Spie, vol. 10575, 2018. Scopus, doi:10.1117/12.2295470.
Source
scopus
Published In
Progress in Biomedical Optics and Imaging Proceedings of Spie
Volume
10575
Publish Date
2018
DOI
10.1117/12.2295470

Improving classification with forced labeling of other related classes: Application to prediction of upstaged ductal carcinoma in situ using mammographic features

© 2018 SPIE. Predicting whether ductal carcinoma in situ (DCIS) identified at core biopsy contains occult invasive disease is an import task since these "upstaged" cases will affect further treatment planning. Therefore, a prediction model that better classifies pure DCIS and upstaged DCIS can help avoid overtreatment and overdiagnosis. In this work, we propose to improve this classification performance with the aid of two other related classes: Atypical Ductal Hyperplasia (ADH) and Invasive Ductal Carcinoma (IDC). Our data set contains mammograms for 230 cases. Specifically, 66 of them are ADH cases; 99 of them are biopsy-proven DCIS cases, of whom 25 were found to contain invasive disease at the time of definitive surgery. The remaining 65 cases were diagnosed with IDC at core biopsy. Our hypothesis is that knowledge can be transferred from training with the easier and more readily available cases of benign but suspicious ADH versus IDC that is already apparent at initial biopsy. Thus, embedding both ADH and IDC cases to the classifier will improve the performance of distinguishing upstaged DCIS from pure DCIS. We extracted 113 mammographic features based on a radiologist's annotation of clusters.Our method then added both ADH and IDC cases during training, where ADH were "force labeled" or treated by the classifier as pure DCIS (negative) cases, and IDC were labeled as upstaged DCIS (positive) cases. A logistic regression classifier was built based on the designed training dataset to perform a prediction of whether biopsy-proven DCIS cases contain invasive cancer. The performance was assessed by repeated 5-fold CrossValidation and Receiver Operating Characteristic(ROC) curve analysis. While prediction performance with only training on DCIS dataset had an average AUC of 0.607(%95CI, 0.479-0.721). By adding both ADH and IDC cases for training, we improved the performance to 0.691(95%CI, 0.581-0.801).

Authors
Hou, R; Shi, B; Grimm, LJ; Mazurowski, MA; Marks, JR; King, LM; Maley, CC; Shelley Hwang, E; Lo, JY
MLA Citation
Hou, R., et al. “Improving classification with forced labeling of other related classes: Application to prediction of upstaged ductal carcinoma in situ using mammographic features.” Progress in Biomedical Optics and Imaging  Proceedings of Spie, vol. 10575, 2018. Scopus, doi:10.1117/12.2293809.
Source
scopus
Published In
Progress in Biomedical Optics and Imaging Proceedings of Spie
Volume
10575
Publish Date
2018
DOI
10.1117/12.2293809

Anatomy and Breast Cancer Staging: Is It Still Relevant?

Breast cancer staging concisely summarizes disease status, creating a framework for assessing and relaying prognostic information. The fundamental concepts and components of breast cancer staging are reviewed. The AJCC Cancer Staging Manual, which includes traditional anatomic factors, now includes additional tumor characteristics: tumor grade, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 status, and (when available) multigene panel testing from the primary tumor. With these updates, staging provides the most reliable system for accurately predicting patient outcome. When the AJCC 8th edition guidelines are adopted, they will more closely reflect tumor biology.

Authors
Plichta, JK; Campbell, BM; Mittendorf, EA; Hwang, ES
MLA Citation
Plichta, Jennifer K., et al. “Anatomy and Breast Cancer Staging: Is It Still Relevant?.” Surg Oncol Clin N Am, vol. 27, no. 1, Jan. 2018, pp. 51–67. Pubmed, doi:10.1016/j.soc.2017.07.010.
PMID
29132565
Source
pubmed
Published In
Surg Oncol Clin N Am
Volume
27
Issue
1
Publish Date
2018
Start Page
51
End Page
67
DOI
10.1016/j.soc.2017.07.010

Molecular determinants of post-mastectomy breast cancer recurrence.

Breast cancer (BC) adjuvant therapy after mastectomy in the setting of 1-3 positive lymph nodes has been controversial. This retrospective Translational Breast Cancer Research Consortium study evaluated molecular aberrations in primary cancers associated with locoregional recurrence (LRR) or distant metastasis (DM) compared to non-recurrent controls. We identified 115 HER2 negative, therapy naïve, T 1-3 and N 0-1 BC patients treated with mastectomy but no post-mastectomy radiotherapy. This included 32 LRR, 34 DM, and 49 controls. RNAseq was performed on primary tumors in 110 patients; with no difference in RNA profiles between patients with LRR, DM, or controls. DNA analysis on 57 primary tumors (17 LRR, 15 DM, and 25 controls) identified significantly more NF1 mutations and mitogen-activated protein kinase (MAPK) pathway gene mutations in patients with LRR (24%, 47%) and DM (27%, 40%) compared to controls (0%, 0%; p < 0.0001 and p = 0.0070, respectively). Three patients had matched primary vs. LRR samples, one patient had a gain of a NF1 mutation in the LRR. There was no significant difference between the groups for PTEN loss or cleaved caspase 3 expression. The mean percentage Ki 67 labeling index was higher in patients with LRR (29.2%) and DM (26%) vs. controls (14%, p = 0.0045). In summary, mutations in the MAPK pathway, specifically NF1, were associated with both LRR and DM, suggesting that alterations in MAPK signaling are associated with a more aggressive tumor phenotype. Validation of these associations in tissues from randomized trials may support targeted therapy to reduce breast cancer recurrence.

Authors
Keene, KS; King, T; Hwang, ES; Peng, B; McGuire, KP; Tapia, C; Zhang, H; Bae, S; Nakhlis, F; Klauber-Demore, N; Meszoely, I; Sabel, MS; Willey, SC; Eterovic, AK; Hudis, C; Wolff, AC; De Los Santos, J; Thompson, A; Mills, GB; Meric-Bernstam, F
MLA Citation
Keene, Kimberly S., et al. “Molecular determinants of post-mastectomy breast cancer recurrence..” Npj Breast Cancer, vol. 4, 2018. Pubmed, doi:10.1038/s41523-018-0089-z.
PMID
30345349
Source
pubmed
Published In
Npj Breast Cancer
Volume
4
Publish Date
2018
Start Page
34
DOI
10.1038/s41523-018-0089-z

The Impact of Autologous Breast Reconstruction on Body Mass Index Patterns in Breast Cancer Patients: A Propensity-Matched Analysis.

BACKGROUND: Weight gain is common in breast cancer patients and increases the risk of recurrence and mortality. The authors assessed the impact of autologous breast reconstruction on body mass index patterns after diagnosis in mastectomy patients. METHODS: Women undergoing therapeutic mastectomy at the authors' institution from 2008 to 2010 were identified. Patients undergoing no breast reconstruction or autologous breast reconstruction were propensity-matched by age at diagnosis, baseline obesity, mastectomy laterality, and adjuvant therapies. Multivariable regression was used to estimate covariate associations with percentage body mass index change and percentage body mass index change greater than 5.0 percent at 1 to 4 years after diagnosis. RESULTS: Of 524 total patients, 80 propensity-matched pairs were identified. In multivariable regression, women undergoing immediate autologous breast reconstruction had reduced body mass index changes after diagnosis, compared with nonreconstruction patients, at 1 year (β = -5.25 percent; p < 0.01), 2 years (β = -8.78 percent; p < 0.01), and 3 years (β = -7.21 percent; p < 0.01). After 4 years, all autologous reconstruction was predictive of reduced body mass index changes (β = -3.54 percent; p = 0.02). Higher body mass index increases were observed among women who were leaner at diagnosis (p < 0.01 at 1 year) and received chemotherapy (p = 0.02 at 3 years; p = 0.04 at 4 years). CONCLUSIONS: Women undergoing autologous breast reconstruction gained less weight after diagnosis than nonreconstruction patients. Normal baseline body mass index and chemotherapy were predictive of greater body mass index increases. These findings may guide targeted weight management strategies in high-risk patients to maximize survival rates. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Authors
Cho, EH; Shammas, RL; Glener, AD; Greenup, RA; Hwang, ES; Hollenbeck, ST
MLA Citation
Cho, Eugenia H., et al. “The Impact of Autologous Breast Reconstruction on Body Mass Index Patterns in Breast Cancer Patients: A Propensity-Matched Analysis..” Plast Reconstr Surg, vol. 140, no. 6, Dec. 2017, pp. 1121–31. Pubmed, doi:10.1097/PRS.0000000000003841.
PMID
29176410
Source
pubmed
Published In
Plast Reconstr Surg
Volume
140
Issue
6
Publish Date
2017
Start Page
1121
End Page
1131
DOI
10.1097/PRS.0000000000003841

Can algorithmically assessed MRI features predict which patients with a preoperative diagnosis of ductal carcinoma in situ are upstaged to invasive breast cancer?

PURPOSE: To assess the ability of algorithmically assessed magnetic resonance imaging (MRI) features to predict the likelihood of upstaging to invasive cancer in newly diagnosed ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: We identified 131 patients at our institution from 2000-2014 with a core needle biopsy-confirmed diagnosis of pure DCIS, a 1.5 or 3T preoperative bilateral breast MRI with nonfat-saturated T1 -weighted MRI sequences, no preoperative therapy before breast MRI, and no prior history of breast cancer. A fellowship-trained radiologist identified the lesion on each breast MRI using a bounding box. Twenty-nine imaging features were then computed automatically using computer algorithms based on the radiologist's annotation. RESULTS: The rate of upstaging of DCIS to invasive cancer in our study was 26.7% (35/131). Out of all imaging variables tested, the information measure of correlation 1, which quantifies spatial dependency in neighboring voxels of the tumor, showed the highest predictive value of upstaging with an area under the curve (AUC) = 0.719 (95% confidence interval [CI]: 0.609-0.829). This feature was statistically significant after adjusting for tumor size (P < 0.001). CONCLUSION: Automatically assessed MRI features may have a role in triaging which patients with a preoperative diagnosis of DCIS are at highest risk for occult invasive disease. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1332-1340.

Authors
Harowicz, MR; Saha, A; Grimm, LJ; Marcom, PK; Marks, JR; Hwang, ES; Mazurowski, MA
MLA Citation
Harowicz, Michael R., et al. “Can algorithmically assessed MRI features predict which patients with a preoperative diagnosis of ductal carcinoma in situ are upstaged to invasive breast cancer?.” J Magn Reson Imaging, vol. 46, no. 5, Nov. 2017, pp. 1332–40. Pubmed, doi:10.1002/jmri.25655.
PMID
28181348
Source
pubmed
Published In
J Magn Reson Imaging
Volume
46
Issue
5
Publish Date
2017
Start Page
1332
End Page
1340
DOI
10.1002/jmri.25655

Imaging Features of Patients Undergoing Active Surveillance for Ductal Carcinoma in Situ.

RATIONALE AND OBJECTIVES: The aim of this study was to describe the imaging appearance of patients undergoing active surveillance for ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: We retrospectively identified 29 patients undergoing active surveillance for DCIS from 2009 to 2014. Twenty-two patients (group 1) refused surgery or were not surgical candidates. Seven patients (group 2) enrolled in a trial of letrozole and deferred surgical excision for 6-12 months. Pathology and imaging results at the initial biopsy and follow-up were recorded. RESULTS: In group 1, the median follow-up was 2.7 years (range: 0.6-13.9 years). Fifteen patients (68%) remained stable. Seven patients (32%) underwent additional biopsies with invasive ductal carcinoma diagnosed in two patients after 3.9 and 3.6 years who developed increasing calcifications and new masses. In group 2, one patient (14%) was upstaged to microinvasive ductal carcinoma at surgery. Among the patients in both groups with calcifications (n = 26), there was no progression to invasive disease among those with stable (50%, 13/26) or decreased (19%, 5/26) calcifications. CONCLUSIONS: Among a DCIS active surveillance cohort, invasive disease progression presented as increasing calcifications and a new mass following more than 3.5 years of stable imaging. In contrast, there was no progression to invasive disease among cases of DCIS with stable or decreasing calcifications. Close imaging is a key follow-up component in active surveillance.

Authors
Grimm, LJ; Ghate, SV; Hwang, ES; Soo, MS
MLA Citation
Grimm, Lars J., et al. “Imaging Features of Patients Undergoing Active Surveillance for Ductal Carcinoma in Situ..” Acad Radiol, vol. 24, no. 11, Nov. 2017, pp. 1364–71. Pubmed, doi:10.1016/j.acra.2017.05.017.
PMID
28705686
Source
pubmed
Published In
Acad Radiol
Volume
24
Issue
11
Publish Date
2017
Start Page
1364
End Page
1371
DOI
10.1016/j.acra.2017.05.017

Surgical Upstaging Rates for Vacuum Assisted Biopsy Proven DCIS: Implications for Active Surveillance Trials.

PURPOSE: This study was designed to determine invasive cancer upstaging rates at surgical excision following vacuum-assisted biopsy of ductal carcinoma in situ (DCIS) among women meeting eligibility for active surveillance trials. METHODS: Patients with vacuum-assisted, biopsy-proven DCIS at a single center from 2008 to 2015 were retrospectively reviewed. Imaging and pathology reports were interrogated for the imaging appearance, tumor grade, hormone receptor status, and presence of comedonecrosis. Subsequent surgical reports were reviewed for upstaging to invasive disease. Cases were classified by eligibility criteria for the COMET, LORIS, and LORD DCIS active surveillance trials. RESULTS: Of 307 DCIS diagnoses, 15 (5%) were low, 95 (31%) intermediate, and 197 (64%) high nuclear grade. The overall upstage rate to invasive disease was 17% (53/307). Eighty-one patients were eligible for the COMET Trial, 74 for the LORIS trial, and 10 for the LORD Trial, although LORIS trial eligibility also included real-time, multiple central pathology review, including elements not routinely reported. The upstaging rates to invasive disease were 6% (5/81), 7% (5/74), and 10% (1/10) for the COMET, LORIS, and LORD trials, respectively. Among upstaged cancers (n = 5), four tumors were Stage IA invasive ductal carcinoma and one was Stage IIA invasive lobular carcinoma; all were node-negative. CONCLUSIONS: DCIS upstaging rates in women eligible for active surveillance trials are low (6-10%), and in this series, all those with invasive disease were early-stage, node-negative. The careful patient selection for DCIS active surveillance trials has a low risk of missing occult invasive cancer and additional studies will determine clinical outcomes.

Authors
Grimm, LJ; Ryser, MD; Partridge, AH; Thompson, AM; Thomas, JS; Wesseling, J; Hwang, ES
MLA Citation
Grimm, Lars J., et al. “Surgical Upstaging Rates for Vacuum Assisted Biopsy Proven DCIS: Implications for Active Surveillance Trials..” Ann Surg Oncol, vol. 24, no. 12, Nov. 2017, pp. 3534–40. Pubmed, doi:10.1245/s10434-017-6018-9.
PMID
28795370
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
24
Issue
12
Publish Date
2017
Start Page
3534
End Page
3540
DOI
10.1245/s10434-017-6018-9

Patient Age and Tumor Subtype Predict the Extent of Axillary Surgery Among Breast Cancer Patients Eligible for the American College of Surgeons Oncology Group Trial Z0011.

BACKGROUND: The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial established the safety of omitting axillary lymph node dissection (ALND) for early-stage breast cancer patients with limited nodal disease undergoing lumpectomy. We examined the extent of axillary surgery among women eligible for Z0011 based on patient age and tumor subtype. METHODS: Patients with cT1-2, cN0 breast cancers and one or two positive nodes diagnosed from 2009 to 2014 and treated with lumpectomy were identified in the National Cancer Data Base. Sentinel lymph node biopsy (SLNB) was defined as the removal of 1-5 nodes and ALND as the removal of 10 nodes or more. Tumor subtype was categorized as luminal, human epidermal growth factor 2-positive (HER2+), or triple-negative. Logistic regression was used to estimate the odds of receiving SLNB alone versus ALND. RESULTS: The inclusion criteria were met by 28,631 patients (21,029 SLNB-alone and 7602 ALND patients). Patients 70 years of age or older were more likely to undergo SLNB alone than ALND (27.0% vs 20.1%; p < 0.001). The radiation therapy use rate was 89.4% after SLNB alone and 89.7% after ALND. In the multivariate analysis, the uptake of Z0011 recommendations increased over time (2014 vs 2009: odds ratio [OR] 13.02; p < 0.001). Younger patients were less likely to undergo SLNB alone than older patients (age <40 vs ≥70: OR 0.59; p < 0.001). Patients with HER2+ (OR 0.89) or triple-negative disease (OR 0.79) (p < 0.001) were less likely to undergo SLNB alone than those with luminal subtypes. CONCLUSIONS: Among women potentially eligible for ACOSOG Z0011, the use of SLNB alone increased over time in all groups, but the extent of axillary surgery differed by patient age and tumor subtype.

Authors
Ong, CT; Thomas, SM; Blitzblau, RC; Fayanju, OM; Park, TS; Plichta, JK; Rosenberger, LH; Hyslop, T; Shelley Hwang, E; Greenup, RA
MLA Citation
Ong, Cecilia T., et al. “Patient Age and Tumor Subtype Predict the Extent of Axillary Surgery Among Breast Cancer Patients Eligible for the American College of Surgeons Oncology Group Trial Z0011..” Ann Surg Oncol, vol. 24, no. 12, Nov. 2017, pp. 3559–66. Pubmed, doi:10.1245/s10434-017-6075-0.
PMID
28879416
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
24
Issue
12
Publish Date
2017
Start Page
3559
End Page
3566
DOI
10.1245/s10434-017-6075-0

Fat Grafting-More Than Just the Hype.

Authors
Hollenbeck, ST; Hwang, ES
MLA Citation
Hollenbeck, Scott T., and E. Shelley Hwang. “Fat Grafting-More Than Just the Hype..” Jama Surg, vol. 152, no. 10, Oct. 2017, pp. 951–52. Pubmed, doi:10.1001/jamasurg.2017.1717.
PMID
28658466
Source
pubmed
Published In
Jama Surg
Volume
152
Issue
10
Publish Date
2017
Start Page
951
End Page
952
DOI
10.1001/jamasurg.2017.1717

Cost Effectiveness of Risk-Reducing Mastectomy versus Surveillance in BRCA Mutation Carriers with a History of Ovarian Cancer.

BACKGROUND: The appropriate management of breast cancer risk in BRCA mutation carriers following ovarian cancer diagnosis remains unclear. We sought to determine the survival benefit and cost effectiveness of risk-reducing mastectomy (RRM) among women with BRCA1/2 mutations following stage II-IV ovarian cancer. DESIGN: We constructed a decision model from a third-party payer perspective to compare annual screening with magnetic resonance imaging (MRI) and mammography to annual screening followed by RRM with reconstruction following ovarian cancer diagnosis. Survival, overall costs, and cost effectiveness were determined by decade at diagnosis using 2015 US dollars. All inputs were obtained from the literature and public databases. Monte Carlo probabilistic sensitivity analysis was performed with a $100,000 willingness-to-pay threshold. RESULTS: The incremental cost-effectiveness ratio (ICER) per year of life saved (YLS) for RRM increased with age and BRCA2 mutation status, with greater survival benefit demonstrated in younger patients with BRCA1 mutations. RRM delayed 5 years in 40-year-old BRCA1 mutation carriers was associated with 5 months of life gained (ICER $72,739/YLS), and in 60-year-old BRCA2 mutation carriers was associated with 0.8 months of life gained (ICER $334,906/YLS). In all scenarios, $/YLS and mastectomies per breast cancer prevented were lowest with RRM performed 5-10 years after ovarian cancer diagnosis. CONCLUSION: For most BRCA1/2 mutation carriers following ovarian cancer diagnosis, RRM performed within 5 years is not cost effective when compared with breast cancer screening. Imaging surveillance should be advocated during the first several years after ovarian cancer diagnosis, after which point the benefits of RRM can be considered based on patient age and BRCA mutation status.

Authors
Gamble, C; Havrilesky, LJ; Myers, ER; Chino, JP; Hollenbeck, S; Plichta, JK; Kelly Marcom, P; Shelley Hwang, E; Kauff, ND; Greenup, RA
MLA Citation
Gamble, Charlotte, et al. “Cost Effectiveness of Risk-Reducing Mastectomy versus Surveillance in BRCA Mutation Carriers with a History of Ovarian Cancer..” Ann Surg Oncol, vol. 24, no. 11, Oct. 2017, pp. 3116–23. Pubmed, doi:10.1245/s10434-017-5995-z.
PMID
28699130
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
24
Issue
11
Publish Date
2017
Start Page
3116
End Page
3123
DOI
10.1245/s10434-017-5995-z

Classifying the evolutionary and ecological features of neoplasms.

Neoplasms change over time through a process of cell-level evolution, driven by genetic and epigenetic alterations. However, the ecology of the microenvironment of a neoplastic cell determines which changes provide adaptive benefits. There is widespread recognition of the importance of these evolutionary and ecological processes in cancer, but to date, no system has been proposed for drawing clinically relevant distinctions between how different tumours are evolving. On the basis of a consensus conference of experts in the fields of cancer evolution and cancer ecology, we propose a framework for classifying tumours that is based on four relevant components. These are the diversity of neoplastic cells (intratumoural heterogeneity) and changes over time in that diversity, which make up an evolutionary index (Evo-index), as well as the hazards to neoplastic cell survival and the resources available to neoplastic cells, which make up an ecological index (Eco-index). We review evidence demonstrating the importance of each of these factors and describe multiple methods that can be used to measure them. Development of this classification system holds promise for enabling clinicians to personalize optimal interventions based on the evolvability of the patient's tumour. The Evo- and Eco-indices provide a common lexicon for communicating about how neoplasms change in response to interventions, with potential implications for clinical trials, personalized medicine and basic cancer research.

Authors
Maley, CC; Aktipis, A; Graham, TA; Sottoriva, A; Boddy, AM; Janiszewska, M; Silva, AS; Gerlinger, M; Yuan, Y; Pienta, KJ; Anderson, KS; Gatenby, R; Swanton, C; Posada, D; Wu, C-I; Schiffman, JD; Hwang, ES; Polyak, K; Anderson, ARA; Brown, JS; Greaves, M; Shibata, D
MLA Citation
Maley, Carlo C., et al. “Classifying the evolutionary and ecological features of neoplasms..” Nat Rev Cancer, vol. 17, no. 10, Oct. 2017, pp. 605–19. Pubmed, doi:10.1038/nrc.2017.69.
PMID
28912577
Source
pubmed
Published In
Nat Rev Cancer
Volume
17
Issue
10
Publish Date
2017
Start Page
605
End Page
619
DOI
10.1038/nrc.2017.69

The Financial Burden of Breast Cancer Treatment

Authors
Greenup, RA; Fish, L; Rushing, C; Peppercorn, J; Hyslop, T; Zafar, Y; Hwang, ES
MLA Citation
Greenup, Rachel Adams, et al. “The Financial Burden of Breast Cancer Treatment.” Journal of Womens Health, vol. 26, no. 9, MARY ANN LIEBERT, INC, 2017, pp. 1022–1022.
Source
wos
Published In
Journal of Women'S Health (2002)
Volume
26
Issue
9
Publish Date
2017
Start Page
1022
End Page
1022

Can Occult Invasive Disease in Ductal Carcinoma In Situ Be Predicted Using Computer-extracted Mammographic Features?

RATIONALE AND OBJECTIVES: This study aimed to determine whether mammographic features assessed by radiologists and using computer algorithms are prognostic of occult invasive disease for patients showing ductal carcinoma in situ (DCIS) only in core biopsy. MATERIALS AND METHODS: In this retrospective study, we analyzed data from 99 subjects with DCIS (74 pure DCIS, 25 DCIS with occult invasion). We developed a computer-vision algorithm capable of extracting 113 features from magnification views in mammograms and combining these features to predict whether a DCIS case will be upstaged to invasive cancer at the time of definitive surgery. In comparison, we also built predictive models based on physician-interpreted features, which included histologic features extracted from biopsy reports and Breast Imaging Reporting and Data System-related mammographic features assessed by two radiologists. The generalization performance was assessed using leave-one-out cross validation with the receiver operating characteristic curve analysis. RESULTS: Using the computer-extracted mammographic features, the multivariate classifier was able to distinguish DCIS with occult invasion from pure DCIS, with an area under the curve for receiver operating characteristic equal to 0.70 (95% confidence interval: 0.59-0.81). The physician-interpreted features including histologic features and Breast Imaging Reporting and Data System-related mammographic features assessed by two radiologists showed mixed results, and only one radiologist's subjective assessment was predictive, with an area under the curve for receiver operating characteristic equal to 0.68 (95% confidence interval: 0.57-0.81). CONCLUSIONS: Predicting upstaging for DCIS based upon mammograms is challenging, and there exists significant interobserver variability among radiologists. However, the proposed computer-extracted mammographic features are promising for the prediction of occult invasion in DCIS.

Authors
Shi, B; Grimm, LJ; Mazurowski, MA; Baker, JA; Marks, JR; King, LM; Maley, CC; Hwang, ES; Lo, JY
MLA Citation
Shi, Bibo, et al. “Can Occult Invasive Disease in Ductal Carcinoma In Situ Be Predicted Using Computer-extracted Mammographic Features?.” Acad Radiol, vol. 24, no. 9, Sept. 2017, pp. 1139–47. Pubmed, doi:10.1016/j.acra.2017.03.013.
PMID
28506510
Source
pubmed
Published In
Acad Radiol
Volume
24
Issue
9
Publish Date
2017
Start Page
1139
End Page
1147
DOI
10.1016/j.acra.2017.03.013

Indications and techniques for biopsy

© 2018 Elsevier Inc. All rights reserved. Several breast biopsy techniques are available for patients presenting with palpable and nonpalpable lesions. Current consensus guidelines recommend percutaneous biopsy as the initial tissue acquisition modality. Image guidance (ultrasound, mammogram, or magnetic resonance imaging) improves accuracy and precision in the biopsy of nonpalpable lesions. Here we review the biopsy techniques in most common use, as well as the indications for each approach.

Authors
Obeng-Gyasi, S; Grimm, LJ; Hwang, ES; Klimberg, VS; Bland, KI
MLA Citation
Obeng-Gyasi, S., et al. “Indications and techniques for biopsy.” The Breast: Comprehensive Management of Benign and Malignant Diseases, 2017, pp. 377-385.e2. Scopus, doi:10.1016/B978-0-323-35955-9.00028-3.
Source
scopus
Publish Date
2017
Start Page
377
End Page
385.e2
DOI
10.1016/B978-0-323-35955-9.00028-3

Reporting and Guidelines in Propensity Score Analysis: A Systematic Review of Cancer and Cancer Surgical Studies.

Background: : Propensity score (PS) analysis is increasingly being used in observational studies, especially in some cancer studies where random assignment is not feasible. This systematic review evaluates the use and reporting quality of PS analysis in oncology studies. Methods: : We searched PubMed to identify the use of PS methods in cancer studies (CS) and cancer surgical studies (CSS) in major medical, cancer, and surgical journals over time and critically evaluated 33 CS published in top medical and cancer journals in 2014 and 2015 and 306 CSS published up to November 26, 2015, without earlier date limits. The quality of reporting in PS analysis was evaluated. It was also compared over time and among journals with differing impact factors. All statistical tests were two-sided. Results: More than 50% of the publications with PS analysis from the past decade occurred within the past two years. Of the studies critically evaluated, a considerable proportion did not clearly provide the variables used to estimate PS (CS 12.1%, CSS 8.8%), incorrectly included non baseline variables (CS 3.4%, CSS 9.3%), neglected the comparison of baseline characteristics (CS 21.9%, CSS 15.6%), or did not report the matching algorithm utilized (CS 19.0%, CSS 36.1%). In CSS, the reporting of the matching algorithm improved in 2014 and 2015 ( P  = .04), and the reporting of variables used to estimate PS was better in top surgery journals ( P  = .008). However, there were no statistically significant differences for the inclusion of non baseline variables and reporting of comparability of baseline characteristics. Conclusions: The use of PS in cancer studies has dramatically increased recently, but there is substantial room for improvement in the quality of reporting even in top journals. Herein we have proposed reporting guidelines for PS analyses that are broadly applicable to different areas of medical research that will allow better evaluation and comparison across studies applying this approach.

Authors
Yao, XI; Wang, X; Speicher, PJ; Hwang, ES; Cheng, P; Harpole, DH; Berry, MF; Schrag, D; Pang, HH
MLA Citation
Yao, Xiaoxin I., et al. “Reporting and Guidelines in Propensity Score Analysis: A Systematic Review of Cancer and Cancer Surgical Studies..” J Natl Cancer Inst, vol. 109, no. 8, Aug. 2017. Pubmed, doi:10.1093/jnci/djw323.
PMID
28376195
Source
pubmed
Published In
J Natl Cancer Inst
Volume
109
Issue
8
Publish Date
2017
DOI
10.1093/jnci/djw323

Suspicious breast calcifications undergoing stereotactic biopsy in women ages 70 and over: Breast cancer incidence by BI-RADS descriptors.

OBJECTIVES: To determine the malignancy rate overall and for specific BI-RADS descriptors in women ≥70 years who undergo stereotactic biopsy for calcifications. METHODS: We retrospectively reviewed 14,577 consecutive mammogram reports in 6839 women ≥70 years to collect 231 stereotactic biopsies of calcifications in 215 women. Cases with missing images or histopathology and calcifications associated with masses, distortion, or asymmetries were excluded. Three breast radiologists determined BI-RADS descriptors by majority. Histology, hormone receptor status, and lymph node status were correlated with BI-RADS descriptors. RESULTS: There were 131 (57 %) benign, 22 (10 %) atypia/lobular carcinomas in situ, 55 (24 %) ductal carcinomas in situ (DCIS), and 23 (10 %) invasive diagnoses. Twenty-seven (51 %) DCIS cases were high-grade. Five (22 %) invasive cases were high-grade, two (9 %) were triple-negative, and three (12 %) were node-positive. Malignancy was found in 49 % (50/103) of fine pleomorphic, 50 % (14/28) of fine linear, 25 % (10/40) of amorphous, 20 % (3/15) of round, 3 % (1/36) of coarse heterogeneous, and 0 % (0/9) of dystrophic calcifications. CONCLUSIONS: Among women ≥70 years that underwent stereotactic biopsy for calcifications only, we observed a high rate of malignancy. Additionally, coarse heterogeneous calcifications may warrant a probable benign designation. KEY POINTS: • Cancer rates of biopsied calcifications in women ≥70 years are high • Radiologists should not dismiss suspicious calcifications in older women • Coarse heterogeneous calcifications may warrant a probable benign designation.

Authors
Grimm, LJ; Johnson, DY; Johnson, KS; Baker, JA; Soo, MS; Hwang, ES; Ghate, SV
MLA Citation
Grimm, Lars J., et al. “Suspicious breast calcifications undergoing stereotactic biopsy in women ages 70 and over: Breast cancer incidence by BI-RADS descriptors..” Eur Radiol, vol. 27, no. 6, June 2017, pp. 2275–81. Pubmed, doi:10.1007/s00330-016-4617-7.
PMID
27752832
Source
pubmed
Published In
Eur Radiol
Volume
27
Issue
6
Publish Date
2017
Start Page
2275
End Page
2281
DOI
10.1007/s00330-016-4617-7

Breast Cancer after Augmentation: Oncologic and Reconstructive Considerations among Women Undergoing Mastectomy.

BACKGROUND: Breast augmentation with subglandular versus subpectoral implants may differentially impact the early detection of breast cancer and treatment recommendations. The authors assessed the impact of prior augmentation on the diagnosis and management of breast cancer in women undergoing mastectomy. METHODS: Breast cancer diagnosis and management were retrospectively analyzed in all women with prior augmentation undergoing therapeutic mastectomy at the authors' institution from 1993 to 2014. Comparison was made to all women with no prior augmentation undergoing mastectomy in 2010. Subanalyses were performed according to prior implant placement. RESULTS: A total of 260 women with (n = 89) and without (n = 171) prior augmentation underwent mastectomy for 95 and 179 breast cancers, respectively. Prior implant placement was subglandular (n = 27) or subpectoral (n = 63) (For five breasts, the placement was unknown). Breast cancer stage at diagnosis (p = 0.19) and detection method (p = 0.48) did not differ for women with and without prior augmentation. Compared to subpectoral augmentation, subglandular augmentation was associated with the diagnosis of invasive breast cancer rather than ductal carcinoma in situ (p = 0.01) and detection by self-palpation rather than screening mammography (p = 0.03). Immediate two-stage implant reconstruction was the preferred reconstructive method in women with augmentation (p < 0.01). CONCLUSIONS: Breast cancer stage at diagnosis was similar for women with and without prior augmentation. Among women with augmentation, however, subglandular implants were associated with more advanced breast tumors commonly detected on palpation rather than mammography. Increased vigilance in breast cancer screening is recommended among women with subglandular augmentation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Authors
Cho, EH; Shammas, RL; Phillips, BT; Greenup, RA; Hwang, ES; Hollenbeck, ST
MLA Citation
Cho, Eugenia H., et al. “Breast Cancer after Augmentation: Oncologic and Reconstructive Considerations among Women Undergoing Mastectomy..” Plast Reconstr Surg, vol. 139, no. 6, June 2017, pp. 1240e-1249e. Pubmed, doi:10.1097/PRS.0000000000003342.
PMID
28538550
Source
pubmed
Published In
Plast Reconstr Surg
Volume
139
Issue
6
Publish Date
2017
Start Page
1240e
End Page
1249e
DOI
10.1097/PRS.0000000000003342

Reply to L.B. Marks et al.

Authors
Recht, A; Comen, EA; Fine, RE; Fleming, GF; Hardenbergh, PH; Ho, AY; Hudis, CA; Hwang, ES; Kirshner, JJ; Morrow, M; Salerno, KE; Sledge, GW; Solin, LJ; Spears, PA; Whelan, TJ; Somerfield, MR; Edge, SB
MLA Citation
Recht, Abram, et al. “Reply to L.B. Marks et al..” J Clin Oncol, vol. 35, no. 11, Apr. 2017, pp. 1258–59. Pubmed, doi:10.1200/JCO.2016.71.3966.
PMID
28068171
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
35
Issue
11
Publish Date
2017
Start Page
1258
End Page
1259
DOI
10.1200/JCO.2016.71.3966

What Can Molecular Diagnostics Add to Locoregional Treatment Recommendations for DCIS?

Authors
Shelley Hwang, E; Thompson, A
MLA Citation
Shelley Hwang, E., and Alastair Thompson. “What Can Molecular Diagnostics Add to Locoregional Treatment Recommendations for DCIS?.” J Natl Cancer Inst, vol. 109, no. 4, Apr. 2017. Pubmed, doi:10.1093/jnci/djw270.
PMID
28376162
Source
pubmed
Published In
J Natl Cancer Inst
Volume
109
Issue
4
Publish Date
2017
DOI
10.1093/jnci/djw270

The Impact of Axillary Surgery on Women with N2-N3 Invasive Breast Cancer

Authors
Park, T; Thomas, S; Rosenberger, L; Fayanju, O; Plichta, J; Ong, C; Hyslop, T; Hwang, ES; Greenup, R
MLA Citation
Park, Tristen, et al. “The Impact of Axillary Surgery on Women with N2-N3 Invasive Breast Cancer.” Annals of Surgical Oncology, vol. 24, SPRINGER, 2017, pp. 162–63.
Source
wos
Published In
Annals of Surgical Oncology
Volume
24
Publish Date
2017
Start Page
162
End Page
163

Surgical resection of the primary tumor in women with stage IV breast cancer: Contemporary practice patterns and survival analysis

Authors
Lane, W; Thomas, SM; Plichta, JK; Fayanju, OM; Rosenberger, LH; Hyslop, T; Hwang, ES; Greenup, RA
MLA Citation
Lane, Whitney, et al. “Surgical resection of the primary tumor in women with stage IV breast cancer: Contemporary practice patterns and survival analysis.” Annals of Surgical Oncology, vol. 24, SPRINGER, 2017, pp. 46–46.
Source
wos
Published In
Annals of Surgical Oncology
Volume
24
Publish Date
2017
Start Page
46
End Page
46

Patient age and tumor subtype predicts adherence to ACOSOG Z0011 recommendations: Analysis of national practice patterns

Authors
Ong, C; Thomas, S; Rosenberger, L; Park, T; Plichta, J; Fayanju, O; Hyslop, T; Hwang, ES; Greenup, R
MLA Citation
Ong, Cecilia, et al. “Patient age and tumor subtype predicts adherence to ACOSOG Z0011 recommendations: Analysis of national practice patterns.” Annals of Surgical Oncology, vol. 24, SPRINGER, 2017, pp. 164–65.
Source
wos
Published In
Annals of Surgical Oncology
Volume
24
Publish Date
2017
Start Page
164
End Page
165

Cost Implications of an Evidence-Based Approach to Radiation Treatment After Lumpectomy for Early-Stage Breast Cancer.

INTRODUCTION:Breast cancer treatment costs are rising, and identification of high-value oncology treatment strategies is increasingly needed. We sought to determine the potential cost savings associated with an evidence-based radiation treatment (RT) approach among women with early-stage breast cancer treated in the United States. PATIENTS AND METHODS:Using the National Cancer Database, we identified women with T1-T2 N0 invasive breast cancers treated with lumpectomy during 2011. Adjuvant RT regimens were categorized as conventionally fractionated whole-breast irradiation, hypofractionated whole-breast irradiation, and omission of RT. National RT patterns were determined, and RT costs were estimated using the Medicare Physician Fee Schedule. RESULTS:Within the 43,247 patient cohort, 64% (n = 27,697) received conventional RT, 13.3% (n = 5,724) received hypofractionated RT, 1.1% (n = 477) received accelerated partial-breast irradiation, and 21.6% (n = 9,349) received no RT. Among patients who were eligible for shorter RT or omission of RT, 57% underwent treatment with longer, more costly regimens. Estimated RT expenditures of the national cohort approximated $420.2 million during 2011, compared with $256.2 million had women been treated with the least expensive regimens for which they were safely eligible. This demonstrated a potential annual savings of $164.0 million, a 39% reduction in associated treatment costs. CONCLUSION:Among women with early-stage breast cancer after lumpectomy, use of an evidence-based approach illustrates an example of high-value care within oncology. Identification of high-value cancer treatment strategies is critically important to maintaining excellence in cancer care while reducing health care expenditures.

Authors
Greenup, RA; Blitzblau, RC; Houck, KL; Sosa, JA; Horton, J; Peppercorn, JM; Taghian, AG; Smith, BL; Hwang, ES
MLA Citation
Greenup, Rachel A., et al. “Cost Implications of an Evidence-Based Approach to Radiation Treatment After Lumpectomy for Early-Stage Breast Cancer..” Journal of Oncology Practice, vol. 13, no. 4, Apr. 2017, pp. e283–90. Epmc, doi:10.1200/JOP.2016.016683.
PMID
28291382
Source
epmc
Published In
Journal of Oncology Practice
Volume
13
Issue
4
Publish Date
2017
Start Page
e283
End Page
e290
DOI
10.1200/JOP.2016.016683

Contralateral Prophylactic Mastectomy: Aligning Patient Preferences and Provider Recommendations.

Authors
Fayanju, OM; Hwang, ES
MLA Citation
Fayanju, Oluwadamilola M., and E. Shelley Hwang. “Contralateral Prophylactic Mastectomy: Aligning Patient Preferences and Provider Recommendations..” Jama Surg, vol. 152, no. 3, Mar. 2017, pp. 282–83. Pubmed, doi:10.1001/jamasurg.2016.4750.
PMID
28002558
Source
pubmed
Published In
Jama Surg
Volume
152
Issue
3
Publish Date
2017
Start Page
282
End Page
283
DOI
10.1001/jamasurg.2016.4750

Clinical Utility of the 12-Gene DCIS Score Assay: Impact on Radiotherapy Recommendations for Patients with Ductal Carcinoma In Situ.

OBJECTIVE: The aim of this study was to determine the impact of the results of the 12-gene DCIS Score assay on (i) radiotherapy recommendations for patients with pure ductal carcinoma in situ (DCIS) following breast-conserving surgery (BCS), and (ii) patient decisional conflict and state anxiety. METHODS: Thirteen sites across the US enrolled patients (March 2014-August 2015) with pure DCIS undergoing BCS. Prospectively collected data included clinicopathologic factors, physician estimates of local recurrence risk, DCIS Score results, and pre-/post-assay radiotherapy recommendations for each patient made by a surgeon and a radiation oncologist. Patients completed pre-/post-assay decisional conflict scale and state-trait anxiety inventory instruments. RESULTS: The analysis cohort included 127 patients: median age 60 years, 80 % postmenopausal, median size 8 mm (39 % ≤5 mm), 70 % grade 1/2, 88 % estrogen receptor-positive, 75 % progesterone receptor-positive, 54 % with comedo necrosis, and 18 % multifocal. Sixty-six percent of patients had low DCIS Score results, 20 % had intermediate DCIS Score results, and 14 % had high DCIS Score results; the median result was 21 (range 0-84). Pre-assay, surgeons and radiation oncologists recommended radiotherapy for 70.9 and 72.4 % of patients, respectively. Post-assay, 26.4 % of overall recommendations changed, including 30.7 and 22.0 % of recommendations by surgeons and radiation oncologists, respectively. Among patients with confirmed completed questionnaires (n = 32), decision conflict (p = 0.004) and state anxiety (p = 0.042) decreased significantly from pre- to post-assay. CONCLUSIONS: Individualized risk estimates from the DCIS Score assay provide valuable information to physicians and patients. Post-assay, in response to DCIS Score results, surgeons changed treatment recommendations more often than radiation oncologists. Further investigation is needed to better understand how such treatment changes may affect clinical outcomes.

Authors
Manders, JB; Kuerer, HM; Smith, BD; McCluskey, C; Farrar, WB; Frazier, TG; Li, L; Leonard, CE; Carter, DL; Chawla, S; Medeiros, LE; Guenther, JM; Castellini, LE; Buchholz, DJ; Mamounas, EP; Wapnir, IL; Horst, KC; Chagpar, A; Evans, SB; Riker, AI; Vali, FS; Solin, LJ; Jablon, L; Recht, A; Sharma, R; Lu, R; Sing, AP; Hwang, ES; White, J; Study investigators and study participants,
MLA Citation
Manders, Jennifer B., et al. “Clinical Utility of the 12-Gene DCIS Score Assay: Impact on Radiotherapy Recommendations for Patients with Ductal Carcinoma In Situ..” Ann Surg Oncol, vol. 24, no. 3, Mar. 2017, pp. 660–68. Pubmed, doi:10.1245/s10434-016-5583-7.
PMID
27704370
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
24
Issue
3
Publish Date
2017
Start Page
660
End Page
668
DOI
10.1245/s10434-016-5583-7

Value of Propensity Score Matching to Study Surgical Outcomes.

Authors
Hwang, ES; Wang, X
MLA Citation
Hwang, E. Shelley, and Xiaofei Wang. “Value of Propensity Score Matching to Study Surgical Outcomes..” Ann Surg, vol. 265, no. 3, Mar. 2017, pp. 457–58. Pubmed, doi:10.1097/SLA.0000000000002125.
PMID
28045717
Source
pubmed
Published In
Ann Surg
Volume
265
Issue
3
Publish Date
2017
Start Page
457
End Page
458
DOI
10.1097/SLA.0000000000002125

KRAS Allelic Imbalance Enhances Fitness and Modulates MAP Kinase Dependence in Cancer.

Investigating therapeutic "outliers" that show exceptional responses to anti-cancer treatment can uncover biomarkers of drug sensitivity. We performed preclinical trials investigating primary murine acute myeloid leukemias (AMLs) generated by retroviral insertional mutagenesis in KrasG12D "knockin" mice with the MEK inhibitor PD0325901 (PD901). One outlier AML responded and exhibited intrinsic drug resistance at relapse. Loss of wild-type (WT) Kras enhanced the fitness of the dominant clone and rendered it sensitive to MEK inhibition. Similarly, human colorectal cancer cell lines with increased KRAS mutant allele frequency were more sensitive to MAP kinase inhibition, and CRISPR-Cas9-mediated replacement of WT KRAS with a mutant allele sensitized heterozygous mutant HCT116 cells to treatment. In a prospectively characterized cohort of patients with advanced cancer, 642 of 1,168 (55%) with KRAS mutations exhibited allelic imbalance. These studies demonstrate that serial genetic changes at the Kras/KRAS locus are frequent in cancer and modulate competitive fitness and MEK dependency.

Authors
Burgess, MR; Hwang, E; Mroue, R; Bielski, CM; Wandler, AM; Huang, BJ; Firestone, AJ; Young, A; Lacap, JA; Crocker, L; Asthana, S; Davis, EM; Xu, J; Akagi, K; Le Beau, MM; Li, Q; Haley, B; Stokoe, D; Sampath, D; Taylor, BS; Evangelista, M; Shannon, K
MLA Citation
Burgess, Michael R., et al. “KRAS Allelic Imbalance Enhances Fitness and Modulates MAP Kinase Dependence in Cancer..” Cell, vol. 168, no. 5, Feb. 2017, pp. 817-829.e15. Pubmed, doi:10.1016/j.cell.2017.01.020.
PMID
28215705
Source
pubmed
Published In
Cell
Volume
168
Issue
5
Publish Date
2017
Start Page
817
End Page
829.e15
DOI
10.1016/j.cell.2017.01.020

Abstract P1-06-06: Evidence for tumor heterogeneity and clonal evolution during invasive progression of breast cancer

Authors
Ding, Y; Marks, JR; King, LM; Hall, AH; Mardis, ER; Rodrigo, AG; Maley, CC; Hwang, E-S
MLA Citation
Ding, Y., et al. “Abstract P1-06-06: Evidence for tumor heterogeneity and clonal evolution during invasive progression of breast cancer.” Poster Session Abstracts, American Association for Cancer Research, 2017. Crossref, doi:10.1158/1538-7445.sabcs16-p1-06-06.
Source
crossref
Published In
Poster Session Abstracts
Publish Date
2017
DOI
10.1158/1538-7445.sabcs16-p1-06-06

H3K27me3 Expression and X Chromosome Inactivation in Breast Carcinoma

Authors
Bean, G; Pekmezci, M; Chen, Y-Y; Hwang, ES; Krings, G
MLA Citation
Bean, Gregory, et al. “H3K27me3 Expression and X Chromosome Inactivation in Breast Carcinoma.” Laboratory Investigation, vol. 97, NATURE PUBLISHING GROUP, 2017, pp. 32A-32A.
Source
wos
Published In
Laboratory Investigation
Volume
97
Publish Date
2017
Start Page
32A
End Page
32A

H3K27me3 Expression and X Chromosome Inactivation in Breast Carcinoma

Authors
Bean, G; Pekmezci, M; Chen, Y-Y; Hwang, ES; Krings, G
MLA Citation
Bean, Gregory, et al. “H3K27me3 Expression and X Chromosome Inactivation in Breast Carcinoma.” Modern Pathology, vol. 30, NATURE PUBLISHING GROUP, 2017, pp. 32A-32A.
Source
wos
Published In
Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc
Volume
30
Publish Date
2017
Start Page
32A
End Page
32A

Prediction of occult invasive disease in ductal carcinoma in situ using computer-extracted mammographic features

© 2017 SPIE. Predicting the risk of occult invasive disease in ductal carcinoma in situ (DCIS) is an important task to help address the overdiagnosis and overtreatment problems associated with breast cancer. In this work, we investigated the feasibility of using computer-extracted mammographic features to predict occult invasive disease in patients with biopsy proven DCIS. We proposed a computer-vision algorithm based approach to extract mammographic features from magnification views of full field digital mammography (FFDM) for patients with DCIS. After an expert breast radiologist provided a region of interest (ROI) mask for the DCIS lesion, the proposed approach is able to segment individual microcalcifications (MCs), detect the boundary of the MC cluster (MCC), and extract 113 mammographic features from MCs and MCC within the ROI. In this study, we extracted mammographic features from 99 patients with DCIS (74 pure DCIS; 25 DCIS plus invasive disease). The predictive power of the mammographic features was demonstrated through binary classifications between pure DCIS and DCIS with invasive disease using linear discriminant analysis (LDA). Before classification, the minimum redundancy Maximum Relevance (mRMR) feature selection method was first applied to choose subsets of useful features. The generalization performance was assessed using Leave-One-Out Cross-Validation and Receiver Operating Characteristic (ROC) curve analysis. Using the computer-extracted mammographic features, the proposed model was able to distinguish DCIS with invasive disease from pure DCIS, with an average classification performance of AUC = 0.61 ± 0.05. Overall, the proposed computer-extracted mammographic features are promising for predicting occult invasive disease in DCIS.

Authors
Shi, B; Grimm, LJ; Mazurowski, MA; Marks, JR; King, LM; Maley, CC; Hwang, ES; Lo, JY
MLA Citation
Shi, B., et al. “Prediction of occult invasive disease in ductal carcinoma in situ using computer-extracted mammographic features.” Progress in Biomedical Optics and Imaging  Proceedings of Spie, vol. 10134, 2017. Scopus, doi:10.1117/12.2255731.
Source
scopus
Published In
Progress in Biomedical Optics and Imaging Proceedings of Spie
Volume
10134
Publish Date
2017
DOI
10.1117/12.2255731

Can upstaging of ductal carcinoma in situ be predicted at biopsy by histologic and mammographic features?

© 2017 SPIE. Reducing the overdiagnosis and overtreatment associated with ductal carcinoma in situ (DCIS) requires accurate prediction of the invasive potential at cancer screening. In this work, we investigated the utility of pre-operative histologic and mammographic features to predict upstaging of DCIS. The goal was to provide intentionally conservative baseline performance using readily available data from radiologists and pathologists and only linear models. We conducted a retrospective analysis on 99 patients with DCIS. Of those 25 were upstaged to invasive cancer at the time of definitive surgery. Pre-operative factors including both the histologic features extracted from stereotactic core needle biopsy (SCNB) reports and the mammographic features annotated by an expert breast radiologist were investigated with statistical analysis. Furthermore, we built classification models based on those features in an attempt to predict the presence of an occult invasive component in DCIS, with generalization performance assessed by receiver operating characteristic (ROC) curve analysis. Histologic features including nuclear grade and DCIS subtype did not show statistically significant differences between cases with pure DCIS and with DCIS plus invasive disease. However, three mammographic features, i.e., the major axis length of DCIS lesion, the BI-RADS level of suspicion, and radiologist's assessment did achieve the statistical significance. Using those three statistically significant features as input, a linear discriminant model was able to distinguish patients with DCIS plus invasive disease from those with pure DCIS, with AUC-ROC equal to 0.62. Overall, mammograms used for breast screening contain useful information that can be perceived by radiologists and help predict occult invasive components in DCIS.

Authors
Shi, B; Grimm, LJ; Mazurowski, MA; Marks, JR; King, LM; Maley, CC; Hwang, ES; Lo, JY
MLA Citation
Shi, B., et al. “Can upstaging of ductal carcinoma in situ be predicted at biopsy by histologic and mammographic features?.” Progress in Biomedical Optics and Imaging  Proceedings of Spie, vol. 10134, 2017. Scopus, doi:10.1117/12.2255847.
Source
scopus
Published In
Progress in Biomedical Optics and Imaging Proceedings of Spie
Volume
10134
Publish Date
2017
DOI
10.1117/12.2255847

Postmastectomy Radiotherapy: An American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Focused Guideline Update.

PURPOSE: A joint American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology panel convened to develop a focused update of the American Society of Clinical Oncology guideline concerning use of postmastectomy radiotherapy (PMRT). METHODS: A recent systematic literature review by Cancer Care Ontario provided the primary evidentiary basis. The joint panel also reviewed targeted literature searches to identify new, potentially practice-changing data. RECOMMENDATIONS: The panel unanimously agreed that available evidence shows that PMRT reduces the risks of locoregional failure (LRF), any recurrence, and breast cancer mortality for patients with T1-2 breast cancer with one to three positive axillary nodes. However, some subsets of these patients are likely to have such a low risk of LRF that the absolute benefit of PMRT is outweighed by its potential toxicities. In addition, the acceptable ratio of benefit to toxicity varies among patients and physicians. Thus, the decision to recommend PMRT requires a great deal of clinical judgment. The panel agreed clinicians making such recommendations for individual patients should consider factors that may decrease the risk of LRF, attenuate the benefit of reduced breast cancer-specific mortality, and/or increase risk of complications resulting from PMRT. When clinicians and patients elect to omit axillary dissection after a positive sentinel node biopsy, the panel recommends that these patients receive PMRT only if there is already sufficient information to justify its use without needing to know additional axillary nodes are involved. Patients with axillary nodal involvement after neoadjuvant systemic therapy should receive PMRT. The panel recommends treatment generally be administered to both the internal mammary nodes and the supraclavicular-axillary apical nodes in addition to the chest wall or reconstructed breast.

Authors
Recht, A; Comen, EA; Fine, RE; Fleming, GF; Hardenbergh, PH; Ho, AY; Hudis, CA; Hwang, ES; Kirshner, JJ; Morrow, M; Salerno, KE; Sledge, GW; Solin, LJ; Spears, PA; Whelan, TJ; Somerfield, MR; Edge, SB
MLA Citation
Recht, Abram, et al. “Postmastectomy Radiotherapy: An American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Focused Guideline Update..” Ann Surg Oncol, vol. 24, no. 1, Jan. 2017, pp. 38–51. Pubmed, doi:10.1245/s10434-016-5558-8.
PMID
27646018
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
24
Issue
1
Publish Date
2017
Start Page
38
End Page
51
DOI
10.1245/s10434-016-5558-8

Deep learning analysis of breast MRIs for prediction of occult invasive disease in ductal carcinoma in situ.

Authors
Zhu, Z; Harowicz, MR; Zhang, J; Saha, A; Grimm, LJ; Hwang, ES; Mazurowski, MA
MLA Citation
Zhu, Zhe, et al. “Deep learning analysis of breast MRIs for prediction of occult invasive disease in ductal carcinoma in situ..” Corr, vol. abs/1711.10577, 2017.
Source
dblp
Published In
Corr
Volume
abs/1711.10577
Publish Date
2017

Postmastectomy Radiotherapy: An American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Focused Guideline Update.

Purpose A joint American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology panel convened to develop a focused update of the American Society of Clinical Oncology guideline concerning use of postmastectomy radiotherapy (PMRT). Methods A recent systematic literature review by Cancer Care Ontario provided the primary evidentiary basis. The joint panel also reviewed targeted literature searches to identify new, potentially practice-changing data. Recommendations The panel unanimously agreed that available evidence shows that PMRT reduces the risks of locoregional failure (LRF), any recurrence, and breast cancer mortality for patients with T1-2 breast cancer with one to three positive axillary nodes. However, some subsets of these patients are likely to have such a low risk of LRF that the absolute benefit of PMRT is outweighed by its potential toxicities. In addition, the acceptable ratio of benefit to toxicity varies among patients and physicians. Thus, the decision to recommend PMRT requires a great deal of clinical judgment. The panel agreed clinicians making such recommendations for individual patients should consider factors that may decrease the risk of LRF, attenuate the benefit of reduced breast cancer-specific mortality, and/or increase risk of complications resulting from PMRT. When clinicians and patients elect to omit axillary dissection after a positive sentinel node biopsy, the panel recommends that these patients receive PMRT only if there is already sufficient information to justify its use without needing to know additional axillary nodes are involved. Patients with axillary nodal involvement after neoadjuvant systemic therapy should receive PMRT. The panel recommends treatment generally be administered to both the internal mammary nodes and the supraclavicular-axillary apical nodes in addition to the chest wall or reconstructed breast.

Authors
Recht, A; Comen, EA; Fine, RE; Fleming, GF; Hardenbergh, PH; Ho, AY; Hudis, CA; Hwang, ES; Kirshner, JJ; Morrow, M; Salerno, KE; Sledge, GW; Solin, LJ; Spears, PA; Whelan, TJ; Somerfield, MR; Edge, SB
MLA Citation
Recht, Abram, et al. “Postmastectomy Radiotherapy: An American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Focused Guideline Update..” J Clin Oncol, vol. 34, no. 36, Dec. 2016, pp. 4431–42. Pubmed, doi:10.1200/JCO.2016.69.1188.
PMID
27646947
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
34
Issue
36
Publish Date
2016
Start Page
4431
End Page
4442
DOI
10.1200/JCO.2016.69.1188

DCIS-Conservative Nonsurgical Management- The Problem of Over-diagnosis: What is the Path Forward?

Authors
Hwang, ES
MLA Citation
Hwang, E. S. “DCIS-Conservative Nonsurgical Management- The Problem of Over-diagnosis: What is the Path Forward?.” Menopause the Journal of the North American Menopause Society, vol. 23, no. 12, LIPPINCOTT WILLIAMS & WILKINS, 2016, pp. 1365–1365.
Source
wos
Published In
Menopause (New York, N.Y.)
Volume
23
Issue
12
Publish Date
2016
Start Page
1365
End Page
1365

Reply to J. Heil et al.

Authors
Hwang, ES; Hyslop, T
MLA Citation
Hwang, E. Shelley, and Terry Hyslop. “Reply to J. Heil et al..” J Clin Oncol, vol. 34, no. 34, Dec. 2016. Pubmed, doi:10.1200/JCO.2016.69.1121.
PMID
27621401
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
34
Issue
34
Publish Date
2016
Start Page
4192
DOI
10.1200/JCO.2016.69.1121

Active Surveillance for DCIS: The Importance of Selection Criteria and Monitoring.

Authors
Grimm, LJ; Shelley Hwang, E
MLA Citation
Grimm, Lars J., and E. Shelley Hwang. “Active Surveillance for DCIS: The Importance of Selection Criteria and Monitoring..” Ann Surg Oncol, vol. 23, no. 13, Dec. 2016, pp. 4134–36. Pubmed, doi:10.1245/s10434-016-5596-2.
PMID
27704372
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
23
Issue
13
Publish Date
2016
Start Page
4134
End Page
4136
DOI
10.1245/s10434-016-5596-2

Comparing Coordinated Versus Sequential Salpingo-Oophorectomy for BRCA1 and BRCA2 Mutation Carriers With Breast Cancer.

BACKGROUND: Women with breast cancer who carry BRCA1 or BRCA2 mutations must also consider risk-reducing salpingo-oophorectomy (RRSO) and how to coordinate this procedure with their breast surgery. We report the factors associated with coordinated versus sequential surgery and compare the outcomes of each. PATIENTS AND METHODS: Patients in our cancer risk database who had breast cancer and a known deleterious BRCA1/2 mutation before undergoing breast surgery were included. Women who chose concurrent RRSO at the time of breast surgery were compared to those who did not. RESULTS: Sixty-two patients knew their mutation carrier status before undergoing breast cancer surgery. Forty-three patients (69%) opted for coordinated surgeries, and 19 (31%) underwent sequential surgeries at a median follow-up of 4.4 years. Women who underwent coordinated surgery were significantly older than those who chose sequential surgery (median age of 45 vs. 39 years; P = .025). There were no differences in comorbidities between groups. Patients who received neoadjuvant chemotherapy were more likely to undergo coordinated surgery (65% vs. 37%; P = .038). Sequential surgery patients had longer hospital stays (4.79 vs. 3.44 days, P = .01) and longer operating times (8.25 vs. 6.38 hours, P = .006) than patients who elected combined surgery. Postoperative complications were minor and were no more likely in either group (odds ratio, 4.76; 95% confidence interval, 0.56-40.6). CONCLUSION: Coordinating RRSO with breast surgery is associated with receipt of neoadjuvant chemotherapy, longer operating times, and hospital stays without an observed increase in complications. In the absence of risk, surgical options can be personalized.

Authors
S Chapman, J; Roddy, E; Panighetti, A; Hwang, S; Crawford, B; Powell, B; Chen, L-M
MLA Citation
S Chapman, Jocelyn, et al. “Comparing Coordinated Versus Sequential Salpingo-Oophorectomy for BRCA1 and BRCA2 Mutation Carriers With Breast Cancer..” Clin Breast Cancer, vol. 16, no. 6, Dec. 2016, pp. 494–99. Pubmed, doi:10.1016/j.clbc.2016.06.016.
PMID
27495996
Source
pubmed
Published In
Clin Breast Cancer
Volume
16
Issue
6
Publish Date
2016
Start Page
494
End Page
499
DOI
10.1016/j.clbc.2016.06.016

Society of Surgical Oncology-American Society for Radiation Oncology-American Society of Clinical Oncology Consensus Guideline on Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in Ductal Carcinoma In Situ.

Background Controversy exists regarding the optimal negative margin width for ductal carcinoma in situ (DCIS) treated with breast-conserving surgery and whole-breast irradiation (WBRT). Methods A multidisciplinary consensus panel used a meta-analysis of margin width and ipsilateral breast tumor recurrence (IBTR) from a systematic review of 20 studies including 7883 patients and other published literature as the evidence base for consensus. Results Negative margins halve the risk of IBTR compared with positive margins defined as ink on DCIS. A 2 mm margin minimizes the risk of IBTR compared with smaller negative margins. More widely clear margins do not significantly decrease IBTR compared with 2 mm margins. Negative margins less than 2 mm alone are not an indication for mastectomy, and factors known to impact rates of IBTR should be considered in determining the need for re-excision. Conclusion The use of a 2 mm margin as the standard for an adequate margin in DCIS treated with WBRT is associated with low rates of IBTR and has the potential to decrease re-excision rates, improve cosmetic outcome, and decrease health care costs. Clinical judgment should be used in determining the need for further surgery in patients with negative margins < 2 mm.

Authors
Morrow, M; Van Zee, KJ; Solin, LJ; Houssami, N; Chavez-MacGregor, M; Harris, JR; Horton, J; Hwang, S; Johnson, PL; Marinovich, ML; Schnitt, SJ; Wapnir, I; Moran, MS
MLA Citation
Morrow, Monica, et al. “Society of Surgical Oncology-American Society for Radiation Oncology-American Society of Clinical Oncology Consensus Guideline on Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in Ductal Carcinoma In Situ..” J Clin Oncol, vol. 34, no. 33, Nov. 2016, pp. 4040–46. Pubmed, doi:10.1200/JCO.2016.68.3573.
PMID
27528719
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
34
Issue
33
Publish Date
2016
Start Page
4040
End Page
4046
DOI
10.1200/JCO.2016.68.3573

Postmastectomy Radiotherapy: An American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Focused Guideline Update.

A joint American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology panel convened to develop a focused update of the American Society of Clinical Oncology guideline concerning use of postmastectomy radiotherapy (PMRT). METHODS: A recent systematic literature review by Cancer Care Ontario provided the primary evidentiary basis. The joint panel also reviewed targeted literature searches to identify new, potentially practice-changing data. RECOMMENDATIONS: The panel unanimously agreed that available evidence shows that PMRT reduces the risks of locoregional failure (LRF), any recurrence, and breast cancer mortality for patients with T1-2 breast cancer with one to three positive axillary nodes. However, some subsets of these patients are likely to have such a low risk of LRF that the absolute benefit of PMRT is outweighed by its potential toxicities. In addition, the acceptable ratio of benefit to toxicity varies among patients and physicians. Thus, the decision to recommend PMRT requires a great deal of clinical judgment. The panel agreed clinicians making such recommendations for individual patients should consider factors that may decrease the risk of LRF, attenuate the benefit of reduced breast cancer-specific mortality, and/or increase risk of complications resulting from PMRT. When clinicians and patients elect to omit axillary dissection after a positive sentinel node biopsy, the panel recommends that these patients receive PMRT only if there is already sufficient information to justify its use without needing to know additional axillary nodes are involved. Patients with axillary nodal involvement after neoadjuvant systemic therapy should receive PMRT. The panel recommends treatment generally be administered to both the internal mammary nodes and the supraclavicular-axillary apical nodes in addition to the chest wall or reconstructed breast.

Authors
Recht, A; Comen, EA; Fine, RE; Fleming, GF; Hardenbergh, PH; Ho, AY; Hudis, CA; Hwang, ES; Kirshner, JJ; Morrow, M; Salerno, KE; Sledge, GW; Solin, LJ; Spears, PA; Whelan, TJ; Somerfield, MR; Edge, SB
MLA Citation
Recht, Abram, et al. “Postmastectomy Radiotherapy: An American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Focused Guideline Update..” Pract Radiat Oncol, vol. 6, no. 6, Nov. 2016, pp. e219–34. Pubmed, doi:10.1016/j.prro.2016.08.009.
PMID
27659727
Source
pubmed
Published In
Pract Radiat Oncol
Volume
6
Issue
6
Publish Date
2016
Start Page
e219
End Page
e234
DOI
10.1016/j.prro.2016.08.009

Society of Surgical Oncology-American Society for Radiation Oncology-American Society of Clinical Oncology Consensus Guideline on Margins for Breast-Conserving Surgery with Whole-Breast Irradiation in Ductal Carcinoma In Situ.

PURPOSE: Controversy exists regarding the optimal negative margin width for ductal carcinoma in situ (DCIS) treated with breast-conserving surgery and whole-breast irradiation. METHODS: A multidisciplinary consensus panel used a meta-analysis of margin width and ipsilateral breast tumor recurrence (IBTR) from a systematic review of 20 studies including 7,883 patients and other published literature as the evidence base for consensus. RESULTS: Negative margins halve the risk of IBTR compared with positive margins defined as ink on DCIS. A 2-mm margin minimizes the risk of IBTR compared with smaller negative margins. More widely clear margins do not significantly decrease IBTR compared with 2-mm margins. Negative margins narrower than 2 mm alone are not an indication for mastectomy, and factors known to affect rates of IBTR should be considered in determining the need for re-excision. CONCLUSION: Use of a 2-mm margin as the standard for an adequate margin in DCIS treated with whole-breast irradiation is associated with lower rates of IBTR and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs. Clinical judgment should be used in determining the need for further surgery in patients with negative margins narrower than 2 mm.

Authors
Morrow, M; Van Zee, KJ; Solin, LJ; Houssami, N; Chavez-MacGregor, M; Harris, JR; Horton, J; Hwang, S; Johnson, PL; Marinovich, ML; Schnitt, SJ; Wapnir, I; Moran, MS
MLA Citation
Morrow, Monica, et al. “Society of Surgical Oncology-American Society for Radiation Oncology-American Society of Clinical Oncology Consensus Guideline on Margins for Breast-Conserving Surgery with Whole-Breast Irradiation in Ductal Carcinoma In Situ..” Ann Surg Oncol, vol. 23, no. 12, Nov. 2016, pp. 3801–10. Pubmed, doi:10.1245/s10434-016-5449-z.
PMID
27527714
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
23
Issue
12
Publish Date
2016
Start Page
3801
End Page
3810
DOI
10.1245/s10434-016-5449-z

Interleukin-10: An Immune-Activating Cytokine in Cancer Immunotherapy.

Authors
Zhang, H; Wang, Y; Hwang, ES; He, Y-W
MLA Citation
Zhang, Hui, et al. “Interleukin-10: An Immune-Activating Cytokine in Cancer Immunotherapy..” J Clin Oncol, vol. 34, no. 29, Oct. 2016, pp. 3576–78. Pubmed, doi:10.1200/JCO.2016.69.6435.
PMID
27573656
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
34
Issue
29
Publish Date
2016
Start Page
3576
End Page
3578
DOI
10.1200/JCO.2016.69.6435

The Impact of the Affordable Care Act on North Carolinian Breast Cancer Patients Seeking Financial Support for Treatment.

BACKGROUND: The Affordable Care Act (ACA) was instated on 23 March 2010 to improve healthcare quality, reduce costs, and increase access. The Pretty in Pink Foundation (PIPF), a non-profit 501(C)(3) organization in North Carolina, provides financial assistance and in-kind support to individuals seeking help with breast cancer care. The objective of this study was to determine whether sociodemographic variables and treatment services varied among PIPF recipients since enactment of the ACA. METHODS: North Carolinians who received financial assistance from the PIPF between 1 January 2013 and 31 December 2014 were included in the study, and the cohort was divided into two groups based on receipt of assistance before or after the enactment of the ACA. Descriptive statistics were tabulated as frequencies. Comparative univariate analysis between both groups was conducted using the χ (2) and Mann-Whitney U tests. All tests were two-sided and a p value <0.05 was considered statistically significant. All analyses were conducted using Stata. RESULTS: Overall, 1016 individuals fulfilled the inclusion criteria, and the median age of the cohort was 49 years (interquartile range 45-55). The ACA groups did not differ significantly by age, race, and sex; however, the groups varied with respect to income, employment, and clinical stage. In addition, the groups differed on the types of services for which they received financial assistance, but no difference was observed between groups with respect to insurance status. CONCLUSION: Since the enactment of the health insurance market component of the ACA, there has been a reduction in subjects receiving assistance from the PIPF; however, no change in their insurance status has been observed.

Authors
Obeng-Gyasi, S; Tolnitch, L; Greenup, RA; Shelley Hwang, E
MLA Citation
Obeng-Gyasi, Samilia, et al. “The Impact of the Affordable Care Act on North Carolinian Breast Cancer Patients Seeking Financial Support for Treatment..” Ann Surg Oncol, vol. 23, no. 10, Oct. 2016, pp. 3412–17. Pubmed, doi:10.1245/s10434-016-5311-3.
PMID
27411550
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
23
Issue
10
Publish Date
2016
Start Page
3412
End Page
3417
DOI
10.1245/s10434-016-5311-3

Current Trends in the Management of Ductal Carcinoma In Situ.

Ductal carcinoma in situ (DCIS), once a rare entity, now comprises up to 30% of newly diagnosed breast cancers detected on mammography. It is now appreciated as a widely heterogeneous disease, with indolent lesions of minimal clinical significance on one end of the spectrum, and aggressive lesions with malignant invasive potential on the other. Therefore, the traditional guideline-concordant approach to treatment with surgery, radiation, and endocrine therapy may lead to overtreatment of certain patients, and insufficient treatment of others. Risk assessment using clinical and molecular prognostic tools is being investigated, addressing the possibility of delineating subpopulations that may be treated with more tailored therapy. This review will summarize the current trends in the diagnosis and management of DCIS and will highlight ongoing trials that are shaping future management of this entity.

Authors
Park, TS; Hwang, ES
MLA Citation
Park, Tristen S., and E. Shelley Hwang. “Current Trends in the Management of Ductal Carcinoma In Situ..” Oncology (Williston Park), vol. 30, no. 9, Sept. 2016, pp. 823–31.
PMID
27633413
Source
pubmed
Published In
Oncology (Williston Park, N.Y.)
Volume
30
Issue
9
Publish Date
2016
Start Page
823
End Page
831

Current Trends in the Management of Ductal Carcinoma In Situ

Ductal carcinoma in situ (DCIS), once a rare entity, now comprises up to 30% of newly diagnosed breast cancers detected on mammography. It is now appreciated as a widely heterogeneous disease, with indolent lesions of minimal clinical significance on one end of the spectrum, and aggressive lesions with malignant invasive potential on the other. Therefore, the traditional guideline-concordant approach to treatment with surgery, radiation, and endocrine therapy may lead to overtreatment of certain patients, and insufficient treatment of others. Risk assessment using clinical and molecular prognostic tools is being investigated, addressing the possibility of delineating subpopulations that may be treated with more tailored therapy. This review will summarize the current trends in the diagnosis and management of DCIS and will highlight ongoing trials that are shaping future management of this entity.

Authors
Park, TS; Hwang, ES
MLA Citation
Park, T. S., and E. S. Hwang. “Current Trends in the Management of Ductal Carcinoma In Situ.” Oncology (Williston Park, N.Y.), vol. 30, no. 9, Sept. 2016, pp. 823–31.
Source
scopus
Published In
Oncology (Williston Park, N.Y.)
Volume
30
Issue
9
Publish Date
2016
Start Page
823
End Page
831

Current Trends in the Management of Ductal Carcinoma In Situ

Ductal carcinoma in situ (DCIS), once a rare entity, now comprises up to 30% of newly diagnosed breast cancers detected on mammography. It is now appreciated as a widely heterogeneous disease, with indolent lesions of minimal clinical significance on one end of the spectrum, and aggressive lesions with malignant invasive potential on the other. Therefore, the traditional guideline-concordant approach to treatment with surgery, radiation, and endocrine therapy may lead to overtreatment of certain patients, and insufficient treatment of others. Risk assessment using clinical and molecular prognostic tools is being investigated, addressing the possibility of delineating subpopulations that may be treated with more tailored therapy. This review will summarize the current trends in the diagnosis and management of DCIS and will highlight ongoing trials that are shaping future management of this entity.

Authors
Park, TS; Hwang, ES
MLA Citation
Park, T. S., and E. S. Hwang. “Current Trends in the Management of Ductal Carcinoma In Situ.” Oncology (Williston Park, N.Y.), vol. 30, no. 9, Sept. 2016, pp. 823–31.
Source
scopus
Published In
Oncology (Williston Park, N.Y.)
Volume
30
Issue
9
Publish Date
2016
Start Page
823
End Page
831

Society of Surgical Oncology-American Society for Radiation Oncology-American Society of Clinical Oncology Consensus Guideline on Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in Ductal Carcinoma in Situ.

PURPOSE: Controversy exists regarding the optimal negative margin width for ductal carcinoma in situ (DCIS) treated with breast-conserving surgery and whole-breast irradiation. METHODS AND MATERIALS: A multidisciplinary consensus panel used a meta-analysis of margin width and ipsilateral breast tumor recurrence (IBTR) from a systematic review of 20 studies including 7883 patients and other published literature as the evidence base for consensus. RESULTS: Negative margins halve the risk of IBTR compared with positive margins defined as ink on DCIS. A 2-mm margin minimizes the risk of IBTR compared with smaller negative margins. More widely clear margins do not significantly decrease IBTR compared with 2-mm margins. Negative margins narrower than 2 mm alone are not an indication for mastectomy, and factors known to affect rates of IBTR should be considered in determining the need for re-excision. CONCLUSION: Use of a 2-mm margin as the standard for an adequate margin in DCIS treated with whole-breast irradiation is associated with lower rates of IBTR and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs. Clinical judgment should be used in determining the need for further surgery in patients with negative margins narrower than 2 mm.

Authors
Morrow, M; Van Zee, KJ; Solin, LJ; Houssami, N; Chavez-MacGregor, M; Harris, JR; Horton, J; Hwang, S; Johnson, PL; Marinovich, ML; Schnitt, SJ; Wapnir, I; Moran, MS
MLA Citation
Morrow, Monica, et al. “Society of Surgical Oncology-American Society for Radiation Oncology-American Society of Clinical Oncology Consensus Guideline on Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in Ductal Carcinoma in Situ..” Pract Radiat Oncol, vol. 6, no. 5, Sept. 2016, pp. 287–95. Pubmed, doi:10.1016/j.prro.2016.06.011.
PMID
27538810
Source
pubmed
Published In
Pract Radiat Oncol
Volume
6
Issue
5
Publish Date
2016
Start Page
287
End Page
295
DOI
10.1016/j.prro.2016.06.011

Can Vascular Patterns on Preoperative Magnetic Resonance Imaging Help Predict Skin Necrosis after Nipple-Sparing Mastectomy?

BACKGROUND: Nipple-areola complex (NAC) and skin flap ischemia and necrosis can occur after nipple-sparing mastectomy (NSM). The purpose of this study was to correlate vascular findings on MRI with outcomes in patients who underwent NSM. STUDY DESIGN: Female patients at a single institution who underwent NSM and had a preoperative breast MRI between 2010 and 2014 were identified. Medical records were reviewed for patient demographics, surgical factors, and complications. Magnetic resonance images were reviewed by 2 radiologists, blinded to outcomes, for the presence of dual vs single blood supply to the breast. The association between blood supply on MRI with ischemic and necrotic complications after NSM was analyzed. RESULTS: One hundred and sixty-four NSM procedures were performed in 105 patients (mean age 45.5 years, range 25 to 69 years) who had a preoperative MRI. The majority of procedures were performed for malignancy (89 of 164 [54.3%]) or prophylaxis (73 of 164 [44.5%]). Nipple-areola complex or skin flap ischemia or necrosis occurred in 40 (24.4%) breasts. Ischemia or necrosis after NSM was less likely to occur in breasts with dual compared with single blood supply (20.8% vs 38.2%; p = 0.03). There was no association between surgical complications and age, BMI, smoking history, previous radiation therapy, indication for NSM, surgical specimen weight, surgical incision type, reconstruction approach, or operating surgeon on univariate analysis. CONCLUSIONS: Preoperative MRI characterization of breast vascularity can be considered when planning NSM. The presence of a dual blood supply to the breast on MRI is associated with a decreased risk of nipple-areola complex and skin flap ischemia and necrosis after NSM.

Authors
Bahl, M; Pien, IJ; Buretta, KJ; Hwang, ES; Greenup, RA; Ghate, SV; Hollenbeck, ST
MLA Citation
Bahl, Manisha, et al. “Can Vascular Patterns on Preoperative Magnetic Resonance Imaging Help Predict Skin Necrosis after Nipple-Sparing Mastectomy?.” J Am Coll Surg, vol. 223, no. 2, Aug. 2016, pp. 279–85. Pubmed, doi:10.1016/j.jamcollsurg.2016.04.045.
PMID
27182036
Source
pubmed
Published In
J Am Coll Surg
Volume
223
Issue
2
Publish Date
2016
Start Page
279
End Page
285
DOI
10.1016/j.jamcollsurg.2016.04.045

Prognostic Impact of 21-Gene Recurrence Score in Patients With Stage IV Breast Cancer: TBCRC 013.

PURPOSE: The objective of this study was to determine whether the 21-gene Recurrence Score (RS) provides clinically meaningful information in patients with de novo stage IV breast cancer enrolled in the Translational Breast Cancer Research Consortium (TBCRC) 013. PATIENTS AND METHODS: TBCRC 013 was a multicenter prospective registry that evaluated the role of surgery of the primary tumor in patients with de novo stage IV breast cancer. From July 2009 to April 2012, 127 patients from 14 sites were enrolled; 109 (86%) patients had pretreatment primary tumor samples suitable for 21-gene RS analysis. Clinical variables, time to first progression (TTP), and 2-year overall survival (OS) were correlated with the 21-gene RS by using log-rank, Kaplan-Meier, and Cox regression. RESULTS: Median patient age was 52 years (21 to 79 years); the majority had hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative (72 [66%]) or hormone receptor-positive/HER2-positive (20 [18%]) breast cancer. At a median follow-up of 29 months, median TTP was 20 months (95% CI, 16 to 26 months), and median survival was 49 months (95% CI, 40 months to not reached). An RS was generated for 101 (93%) primary tumor samples: 22 (23%) low risk (< 18), 29 (28%) intermediate risk (18 to 30); and 50 (49%) high risk (≥ 31). For all patients, RS was associated with TTP (P = .01) and 2-year OS (P = .04). In multivariable Cox regression models among 69 patients with estrogen receptor (ER)-positive/HER2-negative cancer, RS was independently prognostic for TTP (hazard ratio, 1.40; 95% CI, 1.05 to 1.86; P = .02) and 2-year OS (hazard ratio, 1.83; 95% CI, 1.14 to 2.95; P = .013). CONCLUSION: The 21-gene RS is independently prognostic for both TTP and 2-year OS in ER-positive/HER2-negative de novo stage IV breast cancer. Prospective validation is needed to determine the potential role for this assay in the clinical management of this patient subset.

Authors
King, TA; Lyman, JP; Gonen, M; Voci, A; De Brot, M; Boafo, C; Sing, AP; Hwang, ES; Alvarado, MD; Liu, MC; Boughey, JC; McGuire, KP; Van Poznak, CH; Jacobs, LK; Meszoely, IM; Krontiras, H; Babiera, GV; Norton, L; Morrow, M; Hudis, CA
MLA Citation
King, Tari A., et al. “Prognostic Impact of 21-Gene Recurrence Score in Patients With Stage IV Breast Cancer: TBCRC 013..” J Clin Oncol, vol. 34, no. 20, July 2016, pp. 2359–65. Pubmed, doi:10.1200/JCO.2015.63.1960.
PMID
27001590
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
34
Issue
20
Publish Date
2016
Start Page
2359
End Page
2365
DOI
10.1200/JCO.2015.63.1960

Reoperation for Margins After Breast Conservation Surgery: What's Old Is New Again.

Authors
Nag, U; Hwang, ES
MLA Citation
Nag, Uttara, and E. Shelley Hwang. “Reoperation for Margins After Breast Conservation Surgery: What's Old Is New Again..” Jama Surg, vol. 151, no. 7, July 2016. Pubmed, doi:10.1001/jamasurg.2015.5555.
PMID
26885584
Source
pubmed
Published In
Jama Surg
Volume
151
Issue
7
Publish Date
2016
Start Page
656
DOI
10.1001/jamasurg.2015.5555

Contemporary management of ductal carcinoma in situ and lobular carcinoma in situ.

The management of in situ lesions ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS) continues to evolve. These diagnoses now comprise a large burden of mammographically diagnosed cancers, and with a global trend towards more population-based screening, the incidence of these lesions will continue to rise. Because outcomes following treatment for DCIS and LCIS are excellent, there is emerging controversy about what extent of treatment is optimal for both diseases. Here we review the current approaches to the diagnosis and treatment of both DCIS and LCIS. In addition, we will consider potential directions for future management of these lesions.

Authors
Obeng-Gyasi, S; Ong, C; Hwang, ES
MLA Citation
Obeng-Gyasi, Samilia, et al. “Contemporary management of ductal carcinoma in situ and lobular carcinoma in situ..” Chin Clin Oncol, vol. 5, no. 3, June 2016. Pubmed, doi:10.21037/cco.2016.04.02.
PMID
27197512
Source
pubmed
Published In
Chin Clin Oncol
Volume
5
Issue
3
Publish Date
2016
Start Page
32
DOI
10.21037/cco.2016.04.02

Patient-Reported Outcomes After Choice for Contralateral Prophylactic Mastectomy.

PURPOSE: The rate of contralateral prophylactic mastectomies (CPMs) continues to rise, although there is little evidence to support improvement in quality of life (QOL) with CPM. We sought to ascertain whether patient-reported outcomes and, more specifically, QOL differed according to receipt of CPM. METHODS: Volunteers recruited from the Army of Women with a history of breast cancer surgery took an electronically administered survey, which included the BREAST-Q, a well-validated breast surgery outcomes patient-reporting tool, and demographic and treatment-related questions. Descriptive statistics, hypothesis testing, and regression analysis were used to evaluate the association of CPM with four BREAST-Q QOL domains. RESULTS: A total of 7,619 women completed questionnaires; of those eligible, 3,977 had a mastectomy and 1,598 reported receipt of CPM. Women undergoing CPM were younger than those who did not choose CPM. On unadjusted analysis, mean breast satisfaction was higher in the CPM group (60.4 v 57.9, P < .001) and mean physical well-being was lower in the CPM group (74.6 v 76.6, P < .001). On multivariable analysis, the CPM group continued to report higher breast satisfaction (P = .046) and psychosocial well-being (P = .017), but no difference was reported in the no-CPM group in the other QOL domains. CONCLUSION: Choice for CPM was associated with an improvement in breast satisfaction and psychosocial well-being. However, the magnitude of the effect may be too small to be clinically meaningful. Such patient-reported outcomes data are important to consider when counseling women contemplating CPM as part of their breast cancer treatment.

Authors
Hwang, ES; Locklear, TD; Rushing, CN; Samsa, G; Abernethy, AP; Hyslop, T; Atisha, DM
MLA Citation
Hwang, E. Shelley, et al. “Patient-Reported Outcomes After Choice for Contralateral Prophylactic Mastectomy..” J Clin Oncol, vol. 34, no. 13, 2016, pp. 1518–27. Pubmed, doi:10.1200/JCO.2015.61.5427.
PMID
26951322
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
34
Issue
13
Publish Date
2016
Start Page
1518
End Page
1527
DOI
10.1200/JCO.2015.61.5427

Outcomes of Active Surveillance for Ductal Carcinoma in Situ: A Computational Risk Analysis.

BACKGROUND: Ductal carcinoma in situ (DCIS) is a noninvasive breast lesion with uncertain risk for invasive progression. Usual care (UC) for DCIS consists of treatment upon diagnosis, thus potentially overtreating patients with low propensity for progression. One strategy to reduce overtreatment is active surveillance (AS), whereby DCIS is treated only upon detection of invasive disease. Our goal was to perform a quantitative evaluation of outcomes following an AS strategy for DCIS. METHODS: Age-stratified, 10-year disease-specific cumulative mortality (DSCM) for AS was calculated using a computational risk projection model based upon published estimates for natural history parameters, and Surveillance, Epidemiology, and End Results data for outcomes. AS projections were compared with the DSCM for patients who received UC. To quantify the propagation of parameter uncertainty, a 95% projection range (PR) was computed, and sensitivity analyses were performed. RESULTS: Under the assumption that AS cannot outperform UC, the projected median differences in 10-year DSCM between AS and UC when diagnosed at ages 40, 55, and 70 years were 2.6% (PR = 1.4%-5.1%), 1.5% (PR = 0.5%-3.5%), and 0.6% (PR = 0.0%-2.4), respectively. Corresponding median numbers of patients needed to treat to avert one breast cancer death were 38.3 (PR = 19.7-69.9), 67.3 (PR = 28.7-211.4), and 157.2 (PR = 41.1-3872.8), respectively. Sensitivity analyses showed that the parameter with greatest impact on DSCM was the probability of understaging invasive cancer at diagnosis. CONCLUSION: AS could be a viable management strategy for carefully selected DCIS patients, particularly among older age groups and those with substantial competing mortality risks. The effectiveness of AS could be markedly improved by reducing the rate of understaging.

Authors
Ryser, MD; Worni, M; Turner, EL; Marks, JR; Durrett, R; Hwang, ES
MLA Citation
Ryser, Marc D., et al. “Outcomes of Active Surveillance for Ductal Carcinoma in Situ: A Computational Risk Analysis..” J Natl Cancer Inst, vol. 108, no. 5, May 2016. Pubmed, doi:10.1093/jnci/djv372.
PMID
26683405
Source
pubmed
Published In
J Natl Cancer Inst
Volume
108
Issue
5
Publish Date
2016
DOI
10.1093/jnci/djv372

Imaging-Guided Core-Needle Breast Biopsy: Impact of Meditation and Music Interventions on Patient Anxiety, Pain, and Fatigue.

PURPOSE: To evaluate the impact of guided meditation and music interventions on patient anxiety, pain, and fatigue during imaging-guided breast biopsy. METHODS: After giving informed consent, 121 women needing percutaneous imaging-guided breast biopsy were randomized into three groups: (1) guided meditation; (2) music; (3) standard-care control group. During biopsy, the meditation and music groups listened to an audio-recorded, guided, loving-kindness meditation and relaxing music, respectively; the standard-care control group received supportive dialogue from the biopsy team. Immediately before and after biopsy, participants completed questionnaires measuring anxiety (State-Trait Anxiety Inventory Scale), biopsy pain (Brief Pain Inventory), and fatigue (modified Functional Assessment of Chronic Illness Therapy-Fatigue). After biopsy, participants completed questionnaires assessing radiologist-patient communication (modified Questionnaire on the Quality of Physician-Patient Interaction), demographics, and medical history. RESULTS: The meditation and music groups reported significantly greater anxiety reduction (P values < .05) and reduced fatigue after biopsy than the standard-care control group; the standard-care control group reported increased fatigue after biopsy. The meditation group additionally showed significantly lower pain during biopsy, compared with the music group (P = .03). No significant difference in patient-perceived quality of radiologist-patient communication was noted among groups. CONCLUSIONS: Listening to guided meditation significantly lowered biopsy pain during imaging-guided breast biopsy; meditation and music reduced patient anxiety and fatigue without compromising radiologist-patient communication. These simple, inexpensive interventions could improve women's experiences during core-needle breast biopsy.

Authors
Soo, MS; Jarosz, JA; Wren, AA; Soo, AE; Mowery, YM; Johnson, KS; Yoon, SC; Kim, C; Hwang, ES; Keefe, FJ; Shelby, RA
MLA Citation
Soo, Mary Scott, et al. “Imaging-Guided Core-Needle Breast Biopsy: Impact of Meditation and Music Interventions on Patient Anxiety, Pain, and Fatigue..” J Am Coll Radiol, vol. 13, no. 5, May 2016, pp. 526–34. Pubmed, doi:10.1016/j.jacr.2015.12.004.
PMID
26853501
Source
pubmed
Published In
Journal of the American College of Radiology : Jacr
Volume
13
Issue
5
Publish Date
2016
Start Page
526
End Page
534
DOI
10.1016/j.jacr.2015.12.004

Incidence of Adjacent Synchronous Invasive Carcinoma and/or Ductal Carcinoma In-situ in Patients with Lobular Neoplasia on Core Biopsy: Results from a Prospective Multi-Institutional Registry (TBCRC 020).

BACKGROUND: Lobular neoplasia (LN) represents a spectrum of atypical proliferative lesions, including atypical lobular hyperplasia and lobular carcinoma-in-situ. The need for excision for LN found on core biopsy (CB) is controversial. We conducted a prospective multi-institutional trial (TBCRC 20) to determine the rate of upgrade to cancer after excision for pure LN on CB. METHODS: Patients with a CB diagnosis of pure LN were prospectively identified and consented to excision. Cases with discordant imaging and those with additional lesions requiring excision were excluded. Upgrade rates to cancer were quantified on the basis of local and central pathology review. Confidence intervals and sample size were based on exact binomial calculations. RESULTS: A total of 77 of 79 registered patients underwent excision (median age 51 years, range 27-82 years). Two cases (3%; 95% confidence interval 0.3-9) were upgraded to cancer (one tubular carcinoma, one ductal carcinoma-in-situ) at excision per local pathology. Central pathology review of 76 cases confirmed pure LN in the CB in all but two cases. In one case, the tubular carcinoma identified at excision was also found in the CB specimen, and in the other, LN was not identified, yielding an upgrade rate of one case (1%; 95% CI 0.01-7) by central pathology review. CONCLUSIONS: In this prospective study of 77 patients with pure LN on CB, the upgrade rate was 3% by local pathology and 1% by central pathology review, demonstrating that routine excision is not indicated for patients with pure LN on CB and concordant imaging findings.

Authors
Nakhlis, F; Gilmore, L; Gelman, R; Bedrosian, I; Ludwig, K; Hwang, ES; Willey, S; Hudis, C; Iglehart, JD; Lawler, E; Ryabin, NY; Golshan, M; Schnitt, SJ; King, TA
MLA Citation
Nakhlis, Faina, et al. “Incidence of Adjacent Synchronous Invasive Carcinoma and/or Ductal Carcinoma In-situ in Patients with Lobular Neoplasia on Core Biopsy: Results from a Prospective Multi-Institutional Registry (TBCRC 020)..” Ann Surg Oncol, vol. 23, no. 3, Mar. 2016, pp. 722–28. Pubmed, doi:10.1245/s10434-015-4922-4.
PMID
26542585
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
23
Issue
3
Publish Date
2016
Start Page
722
End Page
728
DOI
10.1245/s10434-015-4922-4

Abstract P5-17-03: The 12-gene DCIS score assay: Impact on radiation treatment (XRT) recommendations and clinical utility

Authors
Manders, JB; Kuerer, HM; Smith, BD; McCluskey, C; Farrar, WB; Frazier, TG; Li, L; Leonard, CE; Carter, DL; Chawla, S; Medeiros, LE; Guenther, JM; Castellini, LE; Buchholz, DJ; Mamounas, EP; Wapnir, IL; Horst, KC; Chagpar, A; Evans, SB; Riker, AI; Vali, FS; Solin, LJ; Jablon, L; Recht, A; Sharma, R; Lu, R; Sing, AP; Hwang, ES; White, J
MLA Citation
Manders, J. B., et al. “Abstract P5-17-03: The 12-gene DCIS score assay: Impact on radiation treatment (XRT) recommendations and clinical utility.” Poster Session Abstracts, American Association for Cancer Research, 2016. Crossref, doi:10.1158/1538-7445.sabcs15-p5-17-03.
Source
crossref
Published In
Poster Session Abstracts
Publish Date
2016
DOI
10.1158/1538-7445.sabcs15-p5-17-03

Abstract ES8-3: Endocrine management of premalignant lesions and DCIS

Authors
Hwang, ES
MLA Citation
Hwang, E. S. “Abstract ES8-3: Endocrine management of premalignant lesions and DCIS.” Invited Speaker Abstracts, American Association for Cancer Research, 2016. Crossref, doi:10.1158/1538-7445.sabcs15-es8-3.
Source
crossref
Published In
Invited Speaker Abstracts
Publish Date
2016
DOI
10.1158/1538-7445.sabcs15-es8-3

National Practice Patterns Among Women with Stage IV Breast Cancer Undergoing Surgery at the Primary Site

Authors
Lane, WO; Houck, K; Hwang, ES; Greenup, R
MLA Citation
Lane, W. O., et al. “National Practice Patterns Among Women with Stage IV Breast Cancer Undergoing Surgery at the Primary Site.” Annals of Surgical Oncology, vol. 23, SPRINGER, 2016, pp. S73–S73.
Source
wos
Published In
Annals of Surgical Oncology
Volume
23
Publish Date
2016
Start Page
S73
End Page
S73

Implementation of the Distress Thermometer Among Surgical Breast Cancer Patients at a Comprehensive Breast Center

Authors
Obeng-Gyasi, S; Stashko, I; Power, S; Marcom, PK; Hwang, ES
MLA Citation
Obeng-Gyasi, S., et al. “Implementation of the Distress Thermometer Among Surgical Breast Cancer Patients at a Comprehensive Breast Center.” Annals of Surgical Oncology, vol. 23, SPRINGER, 2016, pp. S71–S71.
Source
wos
Published In
Annals of Surgical Oncology
Volume
23
Publish Date
2016
Start Page
S71
End Page
S71

A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer.

Local recurrence is a common cause of treatment failure for patients with solid tumors. Intraoperative detection of microscopic residual cancer in the tumor bed could be used to decrease the risk of a positive surgical margin, reduce rates of reexcision, and tailor adjuvant therapy. We used a protease-activated fluorescent imaging probe, LUM015, to detect cancer in vivo in a mouse model of soft tissue sarcoma (STS) and ex vivo in a first-in-human phase 1 clinical trial. In mice, intravenous injection of LUM015 labeled tumor cells, and residual fluorescence within the tumor bed predicted local recurrence. In 15 patients with STS or breast cancer, intravenous injection of LUM015 before surgery was well tolerated. Imaging of resected human tissues showed that fluorescence from tumor was significantly higher than fluorescence from normal tissues. LUM015 biodistribution, pharmacokinetic profiles, and metabolism were similar in mouse and human subjects. Tissue concentrations of LUM015 and its metabolites, including fluorescently labeled lysine, demonstrated that LUM015 is selectively distributed to tumors where it is activated by proteases. Experiments in mice with a constitutively active PEGylated fluorescent imaging probe support a model where tumor-selective probe distribution is a determinant of increased fluorescence in cancer. These co-clinical studies suggest that the tumor specificity of protease-activated imaging probes, such as LUM015, is dependent on both biodistribution and enzyme activity. Our first-in-human data support future clinical trials of LUM015 and other protease-sensitive probes.

Authors
Whitley, MJ; Cardona, DM; Lazarides, AL; Spasojevic, I; Ferrer, JM; Cahill, J; Lee, C-L; Snuderl, M; Blazer, DG; Hwang, ES; Greenup, RA; Mosca, PJ; Mito, JK; Cuneo, KC; Larrier, NA; O'Reilly, EK; Riedel, RF; Eward, WC; Strasfeld, DB; Fukumura, D; Jain, RK; Lee, WD; Griffith, LG; Bawendi, MG; Kirsch, DG; Brigman, BE
MLA Citation
Whitley, Melodi Javid, et al. “A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer..” Sci Transl Med, vol. 8, no. 320, Jan. 2016. Pubmed, doi:10.1126/scitranslmed.aad0293.
PMID
26738797
Source
pubmed
Published In
Sci Transl Med
Volume
8
Issue
320
Publish Date
2016
Start Page
320ra4
DOI
10.1126/scitranslmed.aad0293

DNA defects, epigenetics, and gene expression in cancer-adjacent breast: a study from The Cancer Genome Atlas.

Recurrence rates after breast-conserving therapy may depend on genomic characteristics of cancer-adjacent, benign-appearing tissue. Studies have not evaluated recurrence in association with multiple genomic characteristics of cancer-adjacent breast tissue. To estimate the prevalence of DNA defects and RNA expression subtypes in cancer-adjacent, benign-appearing breast tissue at least 2 cm from the tumor margin, cancer-adjacent, pathologically well-characterized, benign-appearing breast tissue specimens from The Cancer Genome Atlas project were analyzed for DNA sequence, copy-number variation, DNA methylation, messenger RNA (mRNA) sequence, and mRNA/microRNA expression. Additional samples were also analyzed by at least one of these genomic data types and associations between genomic characteristics of normal tissue and overall survival were assessed. Approximately 40% of cancer-adjacent, benign-appearing tissues harbored genomic defects in DNA copy number, sequence, methylation, or in RNA sequence, although these defects did not significantly predict 10-year overall survival. Two mRNA/microRNA expression phenotypes were observed, including an active mRNA subtype that was identified in 40% of samples. Controlling for tumor characteristics and the presence of genomic defects, this active subtype was associated with significantly worse 10-year survival among estrogen receptor (ER)-positive cases. This multi-platform analysis of breast cancer-adjacent samples produced genomic findings consistent with current surgical margin guidelines, and provides evidence that extratumoral RNA expression patterns in cancer-adjacent tissue predict overall survival among patients with ER-positive disease.

Authors
Troester, MA; Hoadley, KA; D'Arcy, M; Cherniack, AD; Stewart, C; Koboldt, DC; Robertson, AG; Mahurkar, S; Shen, H; Wilkerson, MD; Sandhu, R; Johnson, NB; Allison, KH; Beck, AH; Yau, C; Bowen, J; Sheth, M; Hwang, ES; Perou, CM; Laird, PW; Ding, L; Benz, CC
MLA Citation
Troester, Melissa A., et al. “DNA defects, epigenetics, and gene expression in cancer-adjacent breast: a study from The Cancer Genome Atlas..” Npj Breast Cancer, vol. 2, 2016. Pubmed, doi:10.1038/npjbcancer.2016.7.
PMID
28721375
Source
pubmed
Published In
Npj Breast Cancer
Volume
2
Publish Date
2016
Start Page
16007
DOI
10.1038/npjbcancer.2016.7

Trends in Treatment Patterns and Outcomes for Ductal Carcinoma In Situ.

BACKGROUND: Impact of contemporary treatment of pre-invasive breast cancer (ductal carcinoma in situ [DCIS]) on long-term outcomes remains poorly defined. We aimed to evaluate national treatment trends for DCIS and to determine their impact on disease-specific (DSS) and overall survival (OS). METHODS: The Surveillance, Epidemiology, and End Results (SEER) registry was queried for patients diagnosed with DCIS from 1991 to 2010. Treatment pattern trends were analyzed using Cochran-Armitage trend test. Survival analyses were performed using inverse probability weights (IPW)-adjusted competing risk analyses for DSS and Cox proportional hazard regression for OS. All tests performed were two-sided. RESULTS: One hundred twenty-one thousand and eighty DCIS patients were identified. The greatest proportion of patients was treated with lumpectomy and radiation therapy (43.0%), followed by lumpectomy alone (26.5%) and unilateral (23.8%) or bilateral mastectomy (4.5%) with significant shifts over time. The rate of sentinel lymph node biopsy increased from 9.7% to 67.1% for mastectomy and from 1.4% to 17.8% for lumpectomy. Compared with mastectomy, OS was higher for lumpectomy with radiation (hazard ratio [HR] = 0.79, 95% confidence interval [CI] = 0.76 to 0.83, P < .001) and lower for lumpectomy alone (HR = 1.17, 95% CI = 1.13 to 1.23, P < .001). IPW-adjusted ten-year DSS was highest in lumpectomy with XRT (98.9%), followed by mastectomy (98.5%), and lumpectomy alone (98.4%). CONCLUSIONS: We identified substantial shifts in treatment patterns for DCIS from 1991 to 2010. When outcomes between locoregional treatment options were compared, we observed greater differences in OS than DSS, likely reflecting both a prevailing patient selection bias as well as clinically negligible differences in breast cancer outcomes between groups.

Authors
Worni, M; Akushevich, I; Greenup, R; Sarma, D; Ryser, MD; Myers, ER; Hwang, ES
MLA Citation
Worni, Mathias, et al. “Trends in Treatment Patterns and Outcomes for Ductal Carcinoma In Situ..” J Natl Cancer Inst, vol. 107, no. 12, Dec. 2015. Pubmed, doi:10.1093/jnci/djv263.
PMID
26424776
Source
pubmed
Published In
J Natl Cancer Inst
Volume
107
Issue
12
Publish Date
2015
Start Page
djv263
DOI
10.1093/jnci/djv263

Preoperative Partial Breast Radiation Therapy: Short-term Imaging Outcomes With Two Unique Treatment Regimens

Authors
Horton, JK; Baker, JA; Blitzblau, R; Georgiade, GS; Hwang, ES; Duffy, EA; Morgan, M; Feigenberg, SJ; Citron, W; Kesmodel, S; Bellavance, E; Drogula, C; Tkaczuk, K; Galandak, J; Nichols, EM
MLA Citation
Horton, J. K., et al. “Preoperative Partial Breast Radiation Therapy: Short-term Imaging Outcomes With Two Unique Treatment Regimens.” International Journal of Radiation Oncology*Biology*Physics, vol. 93, no. 3, Elsevier BV, 2015, pp. E46–E46. Crossref, doi:10.1016/j.ijrobp.2015.07.658.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
93
Issue
3
Publish Date
2015
Start Page
E46
End Page
E46
DOI
10.1016/j.ijrobp.2015.07.658

Preoperative External Beam APBI: Report of Acute Toxicities From 2 Prospective Clinical Trials Using Two Different Fractionation Schemes

Authors
Nichols, E; Feigenberg, SJ; Morgan, M; Citron, W; Kesmodel, S; Bellavance, E; Drogula, C; Tkaczuk, KH; Rosenblatt, P; Georgiade, GS; Hwang, ES; Broadwater, G; Duffy, EA; Blitzblau, R; Horton, JK
MLA Citation
Nichols, E., et al. “Preoperative External Beam APBI: Report of Acute Toxicities From 2 Prospective Clinical Trials Using Two Different Fractionation Schemes.” International Journal of Radiation Oncology*Biology*Physics, vol. 93, no. 3, Elsevier BV, 2015, pp. E49–E49. Crossref, doi:10.1016/j.ijrobp.2015.07.666.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
93
Issue
3
Publish Date
2015
Start Page
E49
End Page
E49
DOI
10.1016/j.ijrobp.2015.07.666

Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer.

Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3, and FOXA1 as ILC enriched features. PTEN loss associated with increased AKT phosphorylation, which was highest in ILC among all breast cancer subtypes. Spatially clustered FOXA1 mutations correlated with increased FOXA1 expression and activity. Conversely, GATA3 mutations and high expression characterized luminal A IDC, suggesting differential modulation of ER activity in ILC and IDC. Proliferation and immune-related signatures determined three ILC transcriptional subtypes associated with survival differences. Mixed IDC/ILC cases were molecularly classified as ILC-like and IDC-like revealing no true hybrid features. This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options.

Authors
Ciriello, G; Gatza, ML; Beck, AH; Wilkerson, MD; Rhie, SK; Pastore, A; Zhang, H; McLellan, M; Yau, C; Kandoth, C; Bowlby, R; Shen, H; Hayat, S; Fieldhouse, R; Lester, SC; Tse, GMK; Factor, RE; Collins, LC; Allison, KH; Chen, Y-Y; Jensen, K; Johnson, NB; Oesterreich, S; Mills, GB; Cherniack, AD; Robertson, G; Benz, C; Sander, C; Laird, PW; Hoadley, KA; King, TA; TCGA Research Network, ; Perou, CM
MLA Citation
Ciriello, Giovanni, et al. “Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer..” Cell, vol. 163, no. 2, Oct. 2015, pp. 506–19. Pubmed, doi:10.1016/j.cell.2015.09.033.
PMID
26451490
Source
pubmed
Published In
Cell
Volume
163
Issue
2
Publish Date
2015
Start Page
506
End Page
519
DOI
10.1016/j.cell.2015.09.033

Human breast cancer invasion and aggression correlates with ECM stiffening and immune cell infiltration.

Tumors are stiff and data suggest that the extracellular matrix stiffening that correlates with experimental mammary malignancy drives tumor invasion and metastasis. Nevertheless, the relationship between tissue and extracellular matrix stiffness and human breast cancer progression and aggression remains unclear. We undertook a biophysical and biochemical assessment of stromal-epithelial interactions in noninvasive, invasive and normal adjacent human breast tissue and in breast cancers of increasingly aggressive subtype. Our analysis revealed that human breast cancer transformation is accompanied by an incremental increase in collagen deposition and a progressive linearization and thickening of interstitial collagen. The linearization of collagen was visualized as an overall increase in tissue birefringence and was most striking at the invasive front of the tumor where the stiffness of the stroma and cellular mechanosignaling were the highest. Amongst breast cancer subtypes we found that the stroma at the invasive region of the more aggressive Basal-like and Her2 tumor subtypes was the most heterogeneous and the stiffest when compared to the less aggressive luminal A and B subtypes. Intriguingly, we quantified the greatest number of infiltrating macrophages and the highest level of TGF beta signaling within the cells at the invasive front. We also established that stroma stiffness and the level of cellular TGF beta signaling positively correlated with each other and with the number of infiltrating tumor-activated macrophages, which was highest in the more aggressive tumor subtypes. These findings indicate that human breast cancer progression and aggression, collagen linearization and stromal stiffening are linked and implicate tissue inflammation and TGF beta.

Authors
Acerbi, I; Cassereau, L; Dean, I; Shi, Q; Au, A; Park, C; Chen, YY; Liphardt, J; Hwang, ES; Weaver, VM
MLA Citation
Acerbi, I., et al. “Human breast cancer invasion and aggression correlates with ECM stiffening and immune cell infiltration..” Integr Biol (Camb), vol. 7, no. 10, Oct. 2015, pp. 1120–34. Pubmed, doi:10.1039/c5ib00040h.
PMID
25959051
Source
pubmed
Published In
Integr Biol (Camb)
Volume
7
Issue
10
Publish Date
2015
Start Page
1120
End Page
1134
DOI
10.1039/c5ib00040h

Preoperative Single-Fraction Partial Breast Radiation Therapy: A Novel Phase 1, Dose-Escalation Protocol With Radiation Response Biomarkers.

PURPOSE: Women with biologically favorable early-stage breast cancer are increasingly treated with accelerated partial breast radiation (PBI). However, treatment-related morbidities have been linked to the large postoperative treatment volumes required for external beam PBI. Relative to external beam delivery, alternative PBI techniques require equipment that is not universally available. To address these issues, we designed a phase 1 trial utilizing widely available technology to 1) evaluate the safety of a single radiation treatment delivered preoperatively to the small-volume, intact breast tumor and 2) identify imaging and genomic markers of radiation response. METHODS AND MATERIALS: Women aged ≥55 years with clinically node-negative, estrogen receptor-positive, and/or progesterone receptor-positive HER2-, T1 invasive carcinomas, or low- to intermediate-grade in situ disease ≤2 cm were enrolled (n=32). Intensity modulated radiation therapy was used to deliver 15 Gy (n=8), 18 Gy (n=8), or 21 Gy (n=16) to the tumor with a 1.5-cm margin. Lumpectomy was performed within 10 days. Paired pre- and postradiation magnetic resonance images and patient tumor samples were analyzed. RESULTS: No dose-limiting toxicity was observed. At a median follow-up of 23 months, there have been no recurrences. Physician-rated cosmetic outcomes were good/excellent, and chronic toxicities were grade 1 to 2 (fibrosis, hyperpigmentation) in patients receiving preoperative radiation only. Evidence of dose-dependent changes in vascular permeability, cell density, and expression of genes regulating immunity and cell death were seen in response to radiation. CONCLUSIONS: Preoperative single-dose radiation therapy to intact breast tumors is well tolerated. Radiation response is marked by early indicators of cell death in this biologically favorable patient cohort. This study represents a first step toward a novel partial breast radiation approach. Preoperative radiation should be tested in future clinical trials because it has the potential to challenge the current treatment paradigm and provide a path forward to identify radiation response biomarkers.

Authors
Horton, JK; Blitzblau, RC; Yoo, S; Geradts, J; Chang, Z; Baker, JA; Georgiade, GS; Chen, W; Siamakpour-Reihani, S; Wang, C; Broadwater, G; Groth, J; Palta, M; Dewhirst, M; Barry, WT; Duffy, EA; Chi, J-TA; Hwang, ES
MLA Citation
Horton, Janet K., et al. “Preoperative Single-Fraction Partial Breast Radiation Therapy: A Novel Phase 1, Dose-Escalation Protocol With Radiation Response Biomarkers..” Int J Radiat Oncol Biol Phys, vol. 92, no. 4, July 2015, pp. 846–55. Pubmed, doi:10.1016/j.ijrobp.2015.03.007.
PMID
26104938
Source
pubmed
Published In
Int J Radiat Oncol Biol Phys
Volume
92
Issue
4
Publish Date
2015
Start Page
846
End Page
855
DOI
10.1016/j.ijrobp.2015.03.007

Lobular breast cancer series: imaging.

The limitations of mammography in the detection and evaluation of invasive lobular carcinoma (ILC) have long been recognized, presenting real clinical challenges in treatment planning for these tumors. However, advances in mammography, ultrasound, and magnetic resonance imaging present opportunities to improve the diagnosis and preoperative assessment of ILC. The evidence supporting the performance of each imaging modality will be reviewed, specifically as it relates to the pathology of ILC and its subtypes. Further, we will discuss emerging technologies that may be employed to enhance the detection rate and ultimately result in more effective screening and staging of ILC.

Authors
Johnson, K; Sarma, D; Hwang, ES
MLA Citation
Johnson, Karen, et al. “Lobular breast cancer series: imaging..” Breast Cancer Res, vol. 17, July 2015. Pubmed, doi:10.1186/s13058-015-0605-0.
PMID
26163296
Source
pubmed
Published In
Breast Cancer Res
Volume
17
Publish Date
2015
Start Page
94
DOI
10.1186/s13058-015-0605-0

Impact of delayed lymphoscintigraphy for sentinel lymphnode biopsy for breast cancer.

BACKGROUND: Despite universal adoption of sentinel lymph node biopsy (SLNB) for breast cancer, there remains no standardized protocol for preoperative lymphoscintographic assessment of sentinel nodes. Both immediate and delayed lymphoscintigraphy are currently utilized, although it is unclear how delayed imaging impacts SLN identification. METHODS: Among patients diagnosed with breast cancer who underwent SLNB at Duke from 2011 to 2012, two protocols for preoperative lymphoscintigraphy were used: protocol A included both immediate and delayed lymphoscintigraphy (n = 152), while protocol B involved immediate lymphoscintigraphy only (n = 103). RESULTS: The overall intraoperative SLN identification rate was 98.4% and did not differ between groups. A lower number of SLN were visualized on the immediate scan using protocol A compared to protocol B (P < 0.001). Although a greater total number of nodes was excised using protocol A, this result was not statistically significant (P = 0.08). Moreover, there was no significant difference in the number of negative SLN between groups (P = 0.51). CONCLUSIONS: We found no significant impact on identification rate or number of SLN excised with the use of delayed versus immediate imaging. These findings support abandoning delayed lymphoscintographic imaging, except in those cases where aberrant drainage is suspected.

Authors
Wang, H; Heck, K; Pruitt, SK; Wong, TZ; Scheri, RP; Georgiade, GS; Ichite, I; Hwang, ES
MLA Citation
Wang, Hanghang, et al. “Impact of delayed lymphoscintigraphy for sentinel lymphnode biopsy for breast cancer..” J Surg Oncol, vol. 111, no. 8, June 2015, pp. 931–34. Pubmed, doi:10.1002/jso.23915.
PMID
25953313
Source
pubmed
Published In
J Surg Oncol
Volume
111
Issue
8
Publish Date
2015
Start Page
931
End Page
934
DOI
10.1002/jso.23915

Abstract P1-10-02: Adjuvant radiation after lumpectomy: A cost comparison of treatment patterns in 43,247 women from the National Cancer Data Base

Authors
Greenup, RA; Blitzblau, R; Houck, K; Horton, J; Howie, L; Palta, M; Mackey, A; Scheri, R; Sosa, JA; Taghian, AG; Peppercorn, J; Smith, BL; Hwang, ES
MLA Citation
Greenup, Rachel A., et al. “Abstract P1-10-02: Adjuvant radiation after lumpectomy: A cost comparison of treatment patterns in 43,247 women from the National Cancer Data Base.” Poster Session Abstracts, American Association for Cancer Research, 2015. Crossref, doi:10.1158/1538-7445.sabcs14-p1-10-02.
Source
crossref
Published In
Poster Session Abstracts
Publish Date
2015
DOI
10.1158/1538-7445.sabcs14-p1-10-02

Abstract P3-07-22: Predictors of neoadjuvant chemotherapy use in women with breast cancer: A review of 169,329 patients from the American College of Surgeons' National Cancer Database

Authors
Howie, LJ; Greenup, R; Houck, K; Sosa, JA; Hwang, ES; Peppercorn, JM
MLA Citation
Howie, Lynn J., et al. “Abstract P3-07-22: Predictors of neoadjuvant chemotherapy use in women with breast cancer: A review of 169,329 patients from the American College of Surgeons' National Cancer Database.” Poster Session Abstracts, American Association for Cancer Research, 2015. Crossref, doi:10.1158/1538-7445.sabcs14-p3-07-22.
Source
crossref
Published In
Poster Session Abstracts
Publish Date
2015
DOI
10.1158/1538-7445.sabcs14-p3-07-22

Implications of HER2-targeted therapy on extent of surgery for early-stage breast cancer.

Authors
Aziz, H; Marcom, PK; Hwang, ES
MLA Citation
Aziz, Hamza, et al. “Implications of HER2-targeted therapy on extent of surgery for early-stage breast cancer..” Ann Surg Oncol, vol. 22, no. 5, May 2015, pp. 1404–05. Pubmed, doi:10.1245/s10434-015-4503-6.
PMID
25777094
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
22
Issue
5
Publish Date
2015
Start Page
1404
End Page
1405
DOI
10.1245/s10434-015-4503-6

Practice patterns in the delivery of radiation therapy after mastectomy among the University of California Athena Breast Health Network.

BACKGROUND: Practice patterns vary with the planning and delivery of PMRT. In our investigation we examined practice patterns in the use of chest wall bolus and a boost among the Athena Breast Health Network (Athena). MATERIALS AND METHODS: Athena is a collaboration among the 5 University of California Medical Centers that aims to integrate clinical care and research. From February 2011 to June 2011, all physicians specializing in the multidisciplinary treatment of breast cancer were invited to take a Web-based practice patterns survey. Sixty-two of the 239 questions focused on radiation therapy practice environment, decision-making processes, and treatment management, including the use of a bolus or boost in PMRT. RESULTS: Ninety-two percent of the radiation oncologists specializing in breast cancer completed the survey. All of the responders use a material to increase the surface dose to the chest wall during PMRT. Materials used included brass mesh, commercial bolus, and custom-designed wax bolus. Fifty percent used tissue equivalent superflab bolus. Fifty-five percent of the respondents routinely use a boost to the chest wall in PMRT. Eighteen percent give a boost depending on the margin status, and 3 of 11 (27%) do not use a boost. CONCLUSION: Our investigation documents practice pattern variation for the use of a PMRT boost and the use of chest wall bolus among the University of California breast cancer radiation oncologists. Further understanding of the practice pattern variation will help guide clinicians in our cancer centers to a more uniform approach in the delivery of PMRT.

Authors
Mayadev, J; Einck, J; Elson, S; Rugo, H; Hwang, S; Bold, R; Daroui, P; McCloskey, S; Yashar, C; Kim, D; Fowble, B
MLA Citation
Mayadev, Jyoti, et al. “Practice patterns in the delivery of radiation therapy after mastectomy among the University of California Athena Breast Health Network..” Clin Breast Cancer, vol. 15, no. 1, Feb. 2015, pp. 43–47. Pubmed, doi:10.1016/j.clbc.2014.07.005.
PMID
25245425
Source
pubmed
Published In
Clin Breast Cancer
Volume
15
Issue
1
Publish Date
2015
Start Page
43
End Page
47
DOI
10.1016/j.clbc.2014.07.005

Monitoring and surveillance following DCIS treatment

© Springer Science+Business Media New York 2015. Currently, more than 20% of breast cancers diagnosed in the USA are ductal carcinoma in situ (DCIS; Brinton et al., J Natl Cancer Inst 100:1643-1648, 2008; DeSantis et al., CA Cancer J Clin 64:52-62, 2014; Ernster et al., J Natl Cancer Inst 94:1546-1554, 2002). Early detection and a low breast-cancer-specific mortality (1-2%; Ernster et al., Arch Intern Med 160:953-958, 2000) have resulted in an increasing number of patients that require clinical follow-up and imaging surveillance after treatment for DCIS. As this population continues to grow, clinical evaluation and management patterns are also evolving, including advances in breast imaging, surgery with or without reconstruction, radiation therapy, and systemic therapies. Clinicians must determine long-term follow-up for patients that have taken a variety of pathways to survivorship. As treatment patterns become more individualized for tumor biology and patient preference, surveillance practices must also evolve and be tailored appropriately for survivorship programs. In this chapter, we review the current guidelines for surveillance after treatment for DCIS and discuss a practical application of these guidelines for a spectrum of DCIS survivors.

Authors
Zakhireh, JL; Shelley Hwang, E
MLA Citation
Zakhireh, J. L., and E. Shelley Hwang. Monitoring and surveillance following DCIS treatment. Jan. 2015, pp. 139–46. Scopus, doi:10.1007/978-1-4939-2035-8_14.
Source
scopus
Publish Date
2015
Start Page
139
End Page
146
DOI
10.1007/978-1-4939-2035-8_14

Preclinical efficacy of MEK inhibition in Nras-mutant AML.

Oncogenic NRAS mutations are highly prevalent in acute myeloid leukemia (AML). Genetic analysis supports the hypothesis that NRAS mutations cooperate with antecedent molecular lesions in leukemogenesis, but have limited independent prognostic significance. Using short hairpin RNA-mediated knockdown in human cell lines and primary mouse leukemias, we show that AML cells with NRAS/Nras mutations are dependent on continued oncogene expression in vitro and in vivo. Using the Mx1-Cre transgene to inactivate a conditional mutant Nras allele, we analyzed hematopoiesis and hematopoietic stem and progenitor cells (HSPCs) under normal and stressed conditions and found that HSPCs lacking Nras expression are functionally equivalent to normal HSPCs in the adult mouse. Treating recipient mice transplanted with primary Nras(G12D) AMLs with 2 potent allosteric mitogen-activated protein kinase kinase (MEK) inhibitors (PD0325901 or trametinib/GlaxoSmithKline 1120212) significantly prolonged survival and reduced proliferation but did not induce apoptosis, promote differentiation, or drive clonal evolution. The phosphatidylinositol 3-kinase inhibitor GDC-0941 was ineffective as a single agent and did not augment the activity of PD0325901. All mice ultimately succumbed to progressive leukemia. Together, these data validate oncogenic N-Ras signaling as a therapeutic target in AML and support testing combination regimens that include MEK inhibitors.

Authors
Burgess, MR; Hwang, E; Firestone, AJ; Huang, T; Xu, J; Zuber, J; Bohin, N; Wen, T; Kogan, SC; Haigis, KM; Sampath, D; Lowe, S; Shannon, K; Li, Q
MLA Citation
Burgess, Michael R., et al. “Preclinical efficacy of MEK inhibition in Nras-mutant AML..” Blood, vol. 124, no. 26, Dec. 2014, pp. 3947–55. Pubmed, doi:10.1182/blood-2014-05-574582.
PMID
25361812
Source
pubmed
Published In
Blood
Volume
124
Issue
26
Publish Date
2014
Start Page
3947
End Page
3955
DOI
10.1182/blood-2014-05-574582

Macrophage IL-10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells.

Blockade of colony-stimulating factor-1 (CSF-1) limits macrophage infiltration and improves response of mammary carcinomas to chemotherapy. Herein we identify interleukin (IL)-10 expression by macrophages as the critical mediator of this phenotype. Infiltrating macrophages were the primary source of IL-10 within tumors, and therapeutic blockade of IL-10 receptor (IL-10R) was equivalent to CSF-1 neutralization in enhancing primary tumor response to paclitaxel and carboplatin. Improved response to chemotherapy was CD8(+) T cell-dependent, but IL-10 did not directly suppress CD8(+) T cells or alter macrophage polarization. Instead, IL-10R blockade increased intratumoral dendritic cell expression of IL-12, which was necessary for improved outcomes. In human breast cancer, expression of IL12A and cytotoxic effector molecules were predictive of pathological complete response rates to paclitaxel.

Authors
Ruffell, B; Chang-Strachan, D; Chan, V; Rosenbusch, A; Ho, CMT; Pryer, N; Daniel, D; Hwang, ES; Rugo, HS; Coussens, LM
MLA Citation
Ruffell, Brian, et al. “Macrophage IL-10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells..” Cancer Cell, vol. 26, no. 5, Nov. 2014, pp. 623–37. Pubmed, doi:10.1016/j.ccell.2014.09.006.
PMID
25446896
Source
pubmed
Published In
Cancer Cell
Volume
26
Issue
5
Publish Date
2014
Start Page
623
End Page
637
DOI
10.1016/j.ccell.2014.09.006

In defense of screening for breast cancer with magnetic resonance imaging--reply.

Authors
Hwang, ES
MLA Citation
Hwang, E. Shelley. “In defense of screening for breast cancer with magnetic resonance imaging--reply..” Jama Intern Med, vol. 174, no. 8, Aug. 2014, pp. 1417–18. Pubmed, doi:10.1001/jamainternmed.2014.803.
PMID
25090184
Source
pubmed
Published In
Jama Internal Medicine
Volume
174
Issue
8
Publish Date
2014
Start Page
1417
End Page
1418
DOI
10.1001/jamainternmed.2014.803

Breast conservation: is the survival better for mastectomy?

Breast conserving therapy with radiation is now firmly established as an effective treatment option for early stage disease, and has been thought for decades to yield equivalent survival outcomes to mastectomy. However, recently published observational studies as well as meta-analyses suggest not only a locoregional, but possibly a systemic benefit to BCT. Choice of surgery and radiation is only one of numerous factors impacting survival following surgery for early stage breast cancer; competing comorbidities and risk of treatment related side effects from radiotherapy must also be considered in order to make optimal treatment recommendations.

Authors
Hwang, ES
MLA Citation
Hwang, E. Shelley. “Breast conservation: is the survival better for mastectomy?.” J Surg Oncol, vol. 110, no. 1, July 2014, pp. 58–61. Pubmed, doi:10.1002/jso.23622.
PMID
24846595
Source
pubmed
Published In
J Surg Oncol
Volume
110
Issue
1
Publish Date
2014
Start Page
58
End Page
61
DOI
10.1002/jso.23622

Risk of positive nonsentinel nodes in women with 1-2 positive sentinel nodes related to age and molecular subtype approximated by receptor status.

We examine risk of positive nonsentinel axillary nodes (NSN) and ≥4 positive nodes in patients with 1-2 positive sentinel nodes (SN) by age and tumor subtype approximated by ER, PR, and Her2 receptor status. Review of two institutional databases demonstrated 284 women undergoing breast conservation between 1997 and 2008 for T1-2 tumors and 1 (229) or 2 (55) positive SN followed by completion dissection. The median number of SN and total axillary nodes removed were 2 (range 1-10) and 14 (range 6-37), respectively. The rate of positive NSNs (p = 0.5) or ≥4 positive nodes (p = 0.6) was not associated with age. NSN were positive in 36% of luminal A, 26% of luminal B, 21% of TN and 38% of Her2+ (p = 0.4). Four or more nodes were present in 17% of luminal A, 13% luminal of B, 0% of TN and 29% of Her2+ (p = 0.1). Microscopic extracapsular extension was significantly associated with having NSNs positive (55% versus 24%, p < 0.0001) and with having total ≥4 nodes positive (33% versus 7%, p < 0.0001). In a population that was largely eligible for ACOSOG Z0011, the risk of positive NSN or ≥4 positive nodes did not vary significantly by age. The TN subgroup had the lowest risk of both positive NSN or ≥4 positive nodes. Several high risk groups with >15% risk for having ≥4 positive nodes were identified. Further data is needed to confirm that ACOSOG Z0011 results are equally applicable to all molecular phenotypes.

Authors
Freedman, GM; Fowble, BL; Li, T; Hwang, ES; Schechter, N; Devarajan, K; Anderson, PR; Sigurdson, ER; Goldstein, LJ; Bleicher, RJ
MLA Citation
Freedman, Gary M., et al. “Risk of positive nonsentinel nodes in women with 1-2 positive sentinel nodes related to age and molecular subtype approximated by receptor status..” Breast J, vol. 20, no. 4, July 2014, pp. 358–63. Pubmed, doi:10.1111/tbj.12276.
PMID
24861613
Source
pubmed
Published In
Breast J
Volume
20
Issue
4
Publish Date
2014
Start Page
358
End Page
363
DOI
10.1111/tbj.12276

Patient-reported outcomes and satisfaction after total skin-sparing mastectomy and immediate expander-implant reconstruction.

BACKGROUND: Total skin-sparing mastectomy (TSSM) with preservation of the nipple-areolar complex skin has become more widely accepted. Few studies looking at outcomes after TSSM and immediate reconstruction have focused on patient-reported outcomes and trends in satisfaction over time. METHODS: Prospective evaluation of patients undergoing TSSM and immediate expander-implant reconstruction was performed. Patients completed the BREAST-Q questionnaire preoperatively and again at 1 month, 6 months, and 1 year postoperatively. Mean scores in each BREAST-Q domain were assessed at each time point. Domains were scored on a 0- to 100-point scale. RESULTS: Survey completion rate was 55%; BREAST-Q scores were calculated from responses from 28 patients. Mean overall satisfaction with breasts declined at 1 month (69.8 to 46.1, P<0.001), but then returned to baseline by 1 year. Mean scores also declined at 1 month in the psychosocial (75.7-67.4, P=0.2) and sexual (58.3-46.7, P=0.06) domains, but returned to baseline by 1 year. Mean nipple satisfaction score was 76.4 at 1 year, with 89% of patients reporting satisfaction with nipple appearance. Satisfaction with nipple position and sensation was lower, with only 56% of patients reporting satisfaction with nipple position and 40% with nipple sensation. CONCLUSIONS: After TSSM and immediate reconstruction, patient satisfaction with their breasts, as well as psychosocial and sexual well-being, returns to baseline by 1 year. Although overall nipple satisfaction is high, patients often report dissatisfaction with nipple position and sensation; appropriate preoperative counseling is important to set realistic expectations.

Authors
Peled, AW; Duralde, E; Foster, RD; Fiscalini, AS; Esserman, LJ; Hwang, ES; Sbitany, H
MLA Citation
Peled, Anne Warren, et al. “Patient-reported outcomes and satisfaction after total skin-sparing mastectomy and immediate expander-implant reconstruction..” Ann Plast Surg, vol. 72 Suppl 1, May 2014, pp. S48–52. Pubmed, doi:10.1097/SAP.0000000000000020.
PMID
24317238
Source
pubmed
Published In
Ann Plast Surg
Volume
72 Suppl 1
Publish Date
2014
Start Page
S48
End Page
S52
DOI
10.1097/SAP.0000000000000020

Cost implications of the SSO-ASTRO consensus guideline on margins for breast-conserving surgery with whole breast irradiation in stage I and II invasive breast cancer.

Authors
Greenup, RA; Peppercorn, J; Worni, M; Hwang, ES
MLA Citation
Greenup, Rachel A., et al. “Cost implications of the SSO-ASTRO consensus guideline on margins for breast-conserving surgery with whole breast irradiation in stage I and II invasive breast cancer..” Ann Surg Oncol, vol. 21, no. 5, May 2014, pp. 1512–14. Pubmed, doi:10.1245/s10434-014-3605-x.
PMID
24577813
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
21
Issue
5
Publish Date
2014
Start Page
1512
End Page
1514
DOI
10.1245/s10434-014-3605-x

Addressing overdiagnosis and overtreatment in cancer: a prescription for change.

A vast range of disorders--from indolent to fast-growing lesions--are labelled as cancer. Therefore, we believe that several changes should be made to the approach to cancer screening and care, such as use of new terminology for indolent and precancerous disorders. We propose the term indolent lesion of epithelial origin, or IDLE, for those lesions (currently labelled as cancers) and their precursors that are unlikely to cause harm if they are left untreated. Furthermore, precursors of cancer or high-risk disorders should not have the term cancer in them. The rationale for this change in approach is that indolent lesions with low malignant potential are common, and screening brings indolent lesions and their precursors to clinical attention, which leads to overdiagnosis and, if unrecognised, possible overtreatment. To minimise that potential, new strategies should be adopted to better define and manage IDLEs. Screening guidelines should be revised to lower the chance of detection of minimal-risk IDLEs and inconsequential cancers with the same energy traditionally used to increase the sensitivity of screening tests. Changing the terminology for some of the lesions currently referred to as cancer will allow physicians to shift medicolegal notions and perceived risk to reflect the evolving understanding of biology, be more judicious about when a biopsy should be done, and organise studies and registries that offer observation or less invasive approaches for indolent disease. Emphasis on avoidance of harm while assuring benefit will improve screening and treatment of patients and will be equally effective in the prevention of death from cancer.

Authors
Esserman, LJ; Thompson, IM; Reid, B; Nelson, P; Ransohoff, DF; Welch, HG; Hwang, S; Berry, DA; Kinzler, KW; Black, WC; Bissell, M; Parnes, H; Srivastava, S
MLA Citation
Esserman, Laura J., et al. “Addressing overdiagnosis and overtreatment in cancer: a prescription for change..” Lancet Oncol, vol. 15, no. 6, May 2014, pp. e234–42. Pubmed, doi:10.1016/S1470-2045(13)70598-9.
PMID
24807866
Source
pubmed
Published In
Lancet Oncol
Volume
15
Issue
6
Publish Date
2014
Start Page
e234
End Page
e242
DOI
10.1016/S1470-2045(13)70598-9

The current clinical value of the DCIS Score.

The management of ductal carcinoma in situ (DCIS) can be controversial. Widespread adoption of mammographic screening has made DCIS a more frequent diagnosis, and increasingly smaller, lower-grade lesions are being detected. DCIS is commonly treated with breast-conserving surgery and radiation. However, there is greater recognition that acceptable cancer control outcomes can be achieved for some patients with breast-conserving surgery alone, with radiotherapy reserved for those at higher risk of in-breast recurrence. The primary clinical dilemma is that there are currently no reliable clinicopathologic features that accurately predict which patients will have a recurrence, but risk stratification is an area of active research. Molecular profiling has the potential to assess recurrence risk based on the individual patient's tumor biology and guide treatment decisions. The DCIS Score is a 12-gene assay intended to support personalized treatment planning for patients with DCIS following local excision. It provides information on local failure risk independent of traditional clinicopathologic features. Our group of expert breast surgeons and radiation oncologists met in December 2013 at the San Antonio Breast Cancer Symposium to discuss current controversies in DCIS management and determine the potential value of the DCIS Score in managing these situations. We concluded that the DCIS Score provides clinically relevant information about personal risk that can guide patient discussions and facilitate shared decision making.

Authors
Wood, WC; Alvarado, M; Buchholz, DJ; Hyams, D; Hwang, S; Manders, J; Park, C; Solin, LJ; White, J; Willey, S
MLA Citation
Wood, William C., et al. “The current clinical value of the DCIS Score..” Oncology (Williston Park), vol. 28 Suppl 2, 2014, pp. C2–3.
PMID
25375000
Source
pubmed
Published In
Oncology (Williston Park, N.Y.)
Volume
28 Suppl 2
Publish Date
2014
Start Page
C2
End Page
C3

Tissue mechanics modulate microRNA-dependent PTEN expression to regulate malignant progression.

Tissue mechanics regulate development and homeostasis and are consistently modified in tumor progression. Nevertheless, the fundamental molecular mechanisms through which altered mechanics regulate tissue behavior and the clinical relevance of these changes remain unclear. We demonstrate that increased matrix stiffness modulates microRNA expression to drive tumor progression through integrin activation of β-catenin and MYC. Specifically, in human and mouse tissue, increased matrix stiffness induced miR-18a to reduce levels of the tumor suppressor phosphatase and tensin homolog (PTEN), both directly and indirectly by decreasing levels of homeobox A9 (HOXA9). Clinically, extracellular matrix stiffness correlated directly and significantly with miR-18a expression in human breast tumor biopsies. miR-18a expression was highest in basal-like breast cancers in which PTEN and HOXA9 levels were lowest, and high miR-18a expression predicted poor prognosis in patients with luminal breast cancers. Our findings identify a mechanically regulated microRNA circuit that can promote malignancy and suggest potential prognostic roles for HOXA9 and miR-18a levels in stratifying patients with luminal breast cancers.

Authors
Mouw, JK; Yui, Y; Damiano, L; Bainer, RO; Lakins, JN; Acerbi, I; Ou, G; Wijekoon, AC; Levental, KR; Gilbert, PM; Hwang, ES; Chen, Y-Y; Weaver, VM
MLA Citation
Mouw, Janna K., et al. “Tissue mechanics modulate microRNA-dependent PTEN expression to regulate malignant progression..” Nat Med, vol. 20, no. 4, Apr. 2014, pp. 360–67. Pubmed, doi:10.1038/nm.3497.
PMID
24633304
Source
pubmed
Published In
Nat Med
Volume
20
Issue
4
Publish Date
2014
Start Page
360
End Page
367
DOI
10.1038/nm.3497

Incidence Patterns of Breast Cancer among Women 35 and Younger at Diagnosis

Authors
Greenup, RA; Arbeev, K; Akushevich, I; Mackey, A; Tolnitch, L; Hwang, ES
MLA Citation
Greenup, R. A., et al. “Incidence Patterns of Breast Cancer among Women 35 and Younger at Diagnosis.” Annals of Surgical Oncology, vol. 21, SPRINGER, 2014, pp. S56–57.
Source
wos
Published In
Annals of Surgical Oncology
Volume
21
Publish Date
2014
Start Page
S56
End Page
S57

The Cumulative Impact of Breast Irradiation on Chest Wall Angiosarcoma: A 40-year Outcome Study

Authors
Mackey, A; Arbeev, K; Akushevich, I; Greenup, R; Georgiade, G; Horton, J; Brennan, MF; Hwang, ES
MLA Citation
Mackey, A., et al. “The Cumulative Impact of Breast Irradiation on Chest Wall Angiosarcoma: A 40-year Outcome Study.” Annals of Surgical Oncology, vol. 21, SPRINGER, 2014, pp. S10–S10.
Source
wos
Published In
Annals of Surgical Oncology
Volume
21
Publish Date
2014
Start Page
S10
End Page
S10

New therapeutic approaches for invasive lobular carcinoma

Invasive lobular carcinoma (ILC) is the second most common histological subtype among newly diagnosed breast cancers. The clinical features of ILC are related to the underlying biology of this disease, which is distinguished by loss of the cell adhesion protein e-cadherin. The resulting poorly cohesive growth pattern is responsible for the comparatively poor detection of ILC both on imaging and palpation. Recent genomic and proteomic discoveries have identified other molecular features of ILC which may lead to its future treatment with more targeted therapy. The presentation, treatment, and outcome of ILC is reviewed and future research directions are considered. © 2014 Springer Science+Business Media.

Authors
Hwang, ES
MLA Citation
Hwang, E. S. “New therapeutic approaches for invasive lobular carcinoma.” Current Breast Cancer Reports, vol. 6, no. 3, Jan. 2014, pp. 159–68. Scopus, doi:10.1007/s12609-014-0158-8.
Source
scopus
Published In
Current Breast Cancer Reports
Volume
6
Issue
3
Publish Date
2014
Start Page
159
End Page
168
DOI
10.1007/s12609-014-0158-8

Should ductal carcinoma in situ be treated?

Authors
Kuerer, HM; Hwang, ES
MLA Citation
Kuerer, H. M., and E. S. Hwang. “Should ductal carcinoma in situ be treated?.” Oncology Report, vol. 10, no. 11, 1 Jan. 2014, pp. 8–10.
Source
scopus
Published In
Oncology Report
Volume
10
Issue
11
Publish Date
2014
Start Page
8
End Page
10

Incidence and consequence of close margins in patients with ductal carcinoma-in situ treated with mastectomy: Is further therapy warranted?

Authors
Sarma, D; Hwang, ES
MLA Citation
Sarma, D., and E. S. Hwang. “Incidence and consequence of close margins in patients with ductal carcinoma-in situ treated with mastectomy: Is further therapy warranted?.” Breast Diseases, vol. 25, no. 4, Jan. 2014, pp. 325–26.
Source
scopus
Published In
Breast Diseases
Volume
25
Issue
4
Publish Date
2014
Start Page
325
End Page
326

Patterns of breast magnetic resonance imaging use: an opportunity for data-driven resource allocation.

Authors
Hwang, ES; Bedrosian, I
MLA Citation
Hwang, E. Shelley, and Isabelle Bedrosian. “Patterns of breast magnetic resonance imaging use: an opportunity for data-driven resource allocation..” Jama Intern Med, vol. 174, no. 1, Jan. 2014, pp. 122–24. Pubmed, doi:10.1001/jamainternmed.2013.10502.
PMID
24247170
Source
pubmed
Published In
Jama Internal Medicine
Volume
174
Issue
1
Publish Date
2014
Start Page
122
End Page
124
DOI
10.1001/jamainternmed.2013.10502

Abstract P5-14-04: Preoperative single-fraction partial breast radiotherapy – Initial results from a novel phase I dose-escalation protocol with exploration of radiation response biomarkers

Authors
Horton, JK; Blitzblau, RC; Yoo, S; Georgiade, GS; Geradts, J; Baker, JA; Chang, Z; Broadwater, G; Barry, W; Duffy, EA; Hwang, ES
MLA Citation
Horton, J. K., et al. “Abstract P5-14-04: Preoperative single-fraction partial breast radiotherapy – Initial results from a novel phase I dose-escalation protocol with exploration of radiation response biomarkers.” Poster Session Abstracts, American Association for Cancer Research, 2013. Crossref, doi:10.1158/0008-5472.sabcs13-p5-14-04.
Source
crossref
Published In
Poster Session Abstracts
Publish Date
2013
DOI
10.1158/0008-5472.sabcs13-p5-14-04

Features of occult invasion in biopsy-proven DCIS at breast MRI.

The purpose of this study is to determine if MRI BI-RADS criteria or radiologist perception correlate with presence of invasive cancer after initial core biopsy of ductal carcinoma in situ (DCIS). Retrospective search spanning 2000-2007 identified all core-biopsy diagnoses of pure DCIS that coincided with preoperative MRI. Two radiologists fellowship-trained in breast imaging categorized lesions according to ACR MRI BI-RADS lexicon and estimated likelihood of occult invasion. Semiquantitative signal enhancement ratio (SER) kinetic analysis was also performed. Results were compared with histopathology. 51 consecutive patients with primary core biopsy-proven DCIS and concurrent MRI were identified. Of these, 13 patients (25%) had invasion at excision. Invasion correlated significantly with presence of a mass for both readers (p = 0.012 and 0.001), rapid initial enhancement for Reader 1 (p = 0.001), and washout kinetics for Reader 2 (p = 0.012). Significant correlation between washout and invasion was confirmed by SER (p = 0.006) when threshold percent enhancement was sufficiently high (130%), corresponding to rapidly enhancing portions of the lesion. Radiologist perception of occult invasion was strongly correlated with true presence of invasion. These results provide evidence that certain BI-RADS MRI criteria, as well as radiologist perception, correlate with occult invasion after an initial core biopsy of DCIS.

Authors
Wisner, DJ; Hwang, ES; Chang, CB; Tso, HH; Joe, BN; Lessing, JN; Lu, Y; Hylton, NM
MLA Citation
Wisner, Dorota Jakubowski, et al. “Features of occult invasion in biopsy-proven DCIS at breast MRI..” Breast J, vol. 19, no. 6, Nov. 2013, pp. 650–58. Pubmed, doi:10.1111/tbj.12201.
PMID
24165314
Source
pubmed
Published In
Breast J
Volume
19
Issue
6
Publish Date
2013
Start Page
650
End Page
658
DOI
10.1111/tbj.12201

Impact of ductal carcinoma in situ terminology on patient treatment preferences.

Authors
Omer, ZB; Hwang, ES; Esserman, LJ; Howe, R; Ozanne, EM
MLA Citation
Omer, Zehra B., et al. “Impact of ductal carcinoma in situ terminology on patient treatment preferences..” Jama Intern Med, vol. 173, no. 19, 28 Oct. 2013, pp. 1830–31. Pubmed, doi:10.1001/jamainternmed.2013.8405.
PMID
23978843
Source
pubmed
Published In
Jama Internal Medicine
Volume
173
Issue
19
Publish Date
2013
Start Page
1830
End Page
1831
DOI
10.1001/jamainternmed.2013.8405

Preoperative Single-Fraction Partial Breast Radiation Therapy: A Novel Phase 1 Dose-Escalation Protocol and Exploration of Breast Cancer Radiation Response

Authors
Horton, JK; Blitzblau, RC; Yoo, S; Georgiade, GS; Geradts, J; Baker, JA; Chang, Z; Duffy, E; Hwang, ES
MLA Citation
Horton, J. K., et al. “Preoperative Single-Fraction Partial Breast Radiation Therapy: A Novel Phase 1 Dose-Escalation Protocol and Exploration of Breast Cancer Radiation Response.” International Journal of Radiation Oncology*Biology*Physics, vol. 87, no. 2, Elsevier BV, 2013, pp. S229–S229. Crossref, doi:10.1016/j.ijrobp.2013.06.594.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
87
Issue
2
Publish Date
2013
Start Page
S229
End Page
S229
DOI
10.1016/j.ijrobp.2013.06.594

Reply to survival after lumpectomy and mastectomy for early stage invasive breast cancer: the effect of age and hormone receptor status.

Authors
Hwang, ES; Clarke, CA; Gomez, SL
MLA Citation
Hwang, E. Shelley, et al. “Reply to survival after lumpectomy and mastectomy for early stage invasive breast cancer: the effect of age and hormone receptor status..” Cancer, vol. 119, no. 17, Sept. 2013, pp. 3254–55. Pubmed, doi:10.1002/cncr.28181.
PMID
23824869
Source
pubmed
Published In
Cancer
Volume
119
Issue
17
Publish Date
2013
Start Page
3254
End Page
3255
DOI
10.1002/cncr.28181

Ductal carcinoma in situ: knowledge of associated risks and prognosis among Latina and non-Latina white women.

While not itself life-threatening, ductal carcinoma in situ (DCIS) can progress to invasive disease if untreated, and confers an increased risk of future breast cancer. We investigated knowledge of DCIS among a cohort of English- and Spanish-speaking Latina and English-speaking non-Latina white women previously treated for DCIS. We examined knowledge of DCIS with four true/false statements about risk of invasive disease, breast cancer recurrence, and prognosis. For each knowledge statement, we modeled the odds of a correct answer by language-ethnicity (English-speaking Latinas, Spanish-speaking Latinas, and English-speaking whites) adjusting for demographics, health history, and treatment factors. Of 710 participants, 52 % were English-speaking whites, 21 % English-speaking Latinas, and 27 % Spanish-speaking Latinas. Less than half (41 %) of participants were aware that DCIS is not life-threatening and only 32 % knew that surgical treatment choice does not impact mortality; whereas two-thirds (67 %) understood that DCIS confers increased risk of future breast cancer, and almost all (92 %) knew that DCIS, if untreated, could become invasive. Only three Spanish-speakers used professional interpreters during discussions with their physicians. In adjusted analyses, compared to English-speaking whites, both English- and Spanish-speaking Latinas had significantly lower odds of knowing that DCIS was not life-threatening (OR, 95 % CI 0.6, 0.4-0.9 and 0.5, 0.3-0.9, respectively). In contrast, Spanish-speaking Latinas had a twofold higher odds of knowing that DCIS increases risk of future breast cancer (OR, 95 % CI 2.6, 1.6-4.4), but English-speaking Latinas were no different from English-speaking whites. Our data suggest that physicians are more successful at conveying the risks conferred by DCIS than the nuances of DCIS as a non-life-threatening diagnosis. This uneven communication is most marked for Spanish-speaking Latinas. In addition to the use of professional interpreters, efforts to create culturally and linguistically standardized information could improve knowledge and engagement in informed decision making for all DCIS patients.

Authors
Parikh, AR; Kaplan, CP; Burke, NJ; Livaudais-Toman, J; Hwang, ES; Karliner, LS
MLA Citation
Parikh, Aparna R., et al. “Ductal carcinoma in situ: knowledge of associated risks and prognosis among Latina and non-Latina white women..” Breast Cancer Res Treat, vol. 141, no. 2, Sept. 2013, pp. 261–68. Pubmed, doi:10.1007/s10549-013-2676-x.
PMID
23996141
Source
pubmed
Published In
Breast Cancer Res Treat
Volume
141
Issue
2
Publish Date
2013
Start Page
261
End Page
268
DOI
10.1007/s10549-013-2676-x

New treatment paradigms for patients with ductal carcinoma in situ

One of the most poorly understood clinical diagnoses in breast cancer is ductal carcinoma in situ (DCIS), which now accounts for almost one third of all mammographically detected malignancies. Detection and diagnosis of DCIS have improved, and mature data from randomized controlled trials of lumpectomy for DCIS have provided some measure of the magnitude of benefit to be derived from adjuvant treatments. The past 5 years have seen the emergence of molecular prognostic tools, which together with clinical factors have the potential to allow better selection of individualized therapies for these heterogeneous lesions. Ongoing and future research to identify which patients with DCIS can be safely managed with active surveillance are underway and will create opportunities to better understand the biology of this disease, thereby informing treatment strategies that are more closely aligned with the invasive potential of specific DCIS subtypes. © 2013 Springer Science+Business Media New York.

Authors
Mackey, A; Greenup, R; Hwang, ES
MLA Citation
Mackey, A., et al. “New treatment paradigms for patients with ductal carcinoma in situ.” Current Breast Cancer Reports, vol. 5, no. 2, June 2013, pp. 86–98. Scopus, doi:10.1007/s12609-013-0109-9.
Source
scopus
Published In
Current Breast Cancer Reports
Volume
5
Issue
2
Publish Date
2013
Start Page
86
End Page
98
DOI
10.1007/s12609-013-0109-9

Ductal carcinoma in situ (DCIS): posttreatment follow-up care among Latina and non-Latina White women.

BACKGROUND: There is a lack of information about posttreatment care among patients with ductal carcinoma in situ (DCIS). This study compares posttreatment care by ethnicity-language and physician specialty among Latina and White women with DCIS. METHODS: Latina and White women diagnosed with DCIS between 2002 and 2005 identified through the California Cancer Registry completed a telephone survey in 2006. Main outcomes were breast surveillance, lifestyle counseling, and follow-up physician specialty. KEY RESULTS: Of 742 women (396 White, 349 Latinas), most (90 %) had at least one clinical breast exam (CBE). Among women treated with breast-conserving surgery (BCS; N = 503), 76 % had received at least two mammograms. While 92 % of all women had follow-up with a breast specialist, Spanish-speaking Latinas had the lowest specialist follow-up rates (84 %) of all groups. Lifestyle counseling was low with only 53 % discussing exercise, 43 % weight, and 31 % alcohol in relation to their DCIS. In multivariable analysis, Spanish-speaking Latinas with BCS had lower odds of receiving the recommended mammography screening in the year following treatment compared to Whites (OR 0.5; 95 % CI, 0.2-0.9). Regardless of ethnicity-language, seeing both a specialist and primary care physician increased the odds of mammography screening and CBE (OR 1.6; 95 % CI, 1.2-2.3 and OR 1.9; 95 % CI, 1.3-2.8), as well as having discussions about exercise, weight, and alcohol use, compared to seeing a specialist only. CONCLUSIONS: Most women reported appropriate surveillance after DCIS treatment. However, our results suggest less adequate follow-up for Spanish-speaking Latinas, possibly due to language barriers or insurance access. IMPLICATIONS FOR CANCER SURVIVORS: Follow-up with a primary care provider in addition to a breast specialist increases receipt of appropriate follow-up for all women.

Authors
López, ME; Kaplan, CP; Nápoles, AM; Livaudais, JC; Hwang, ES; Stewart, SL; Bloom, J; Karliner, L
MLA Citation
López, Mónica E., et al. “Ductal carcinoma in situ (DCIS): posttreatment follow-up care among Latina and non-Latina White women..” J Cancer Surviv, vol. 7, no. 2, June 2013, pp. 219–26. Pubmed, doi:10.1007/s11764-012-0262-6.
PMID
23408106
Source
pubmed
Published In
J Cancer Surviv
Volume
7
Issue
2
Publish Date
2013
Start Page
219
End Page
226
DOI
10.1007/s11764-012-0262-6

FOXP3-positive regulatory T lymphocytes and epithelial FOXP3 expression in synchronous normal, ductal carcinoma in situ, and invasive cancer of the breast.

FOXP3-expressing T regulatory lymphocytes (Tregs) have been described as putative mediators of immune tolerance, and thus facilitators of tumor growth. When found in association with various malignancies, Tregs are generally markers of poor clinical outcome. However, it is unknown whether they are also associated with cancer progression. We evaluated quantitative FOXP3 expression in lymphocytes as well as in epithelial cells in a set of thirty-two breast tumors with synchronous normal epithelium, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) components. Tumors were stained for FOXP3 and CD3 expression and Tregs quantified by determining the ratio of colocalized FOXP3 and CD3 relative to 1) total CD3-expressing lymphocytes and 2) to FOXP3-expressing epithelial cells. The median proportion of FOXP3-expressing CD3 cells significantly increased with malignant progression from normal to DCIS to IDC components (0.005, 0.019 and 0.030, respectively; p ≤ 0.0001 for normal vs. IDC and p = 0.004 for DCIS vs. IDC). The median intensity of epithelial FOXP3 expression was also increased with invasive progression and most markedly augmented between normal and DCIS components (0.130 vs. 0.175, p ≤ 0.0001). Both Treg infiltration and epithelial FOXP3 expression were higher in grade 3 vs. grade 1 tumors (p = 0.014 for Tregs, p = 0.038 for epithelial FOXP3), but did not vary significantly with hormone receptor status, size of invasive tumor, lymph node status, or disease stage. Notably, Treg infiltration significantly correlated with epithelial up-regulation of FOXP3 expression (p = 0.013 for normal, p = 0.001 for IDC). These findings implicate both Treg infiltration and up-regulated epithelial FOXP3 expression in breast cancer progression.

Authors
Lal, A; Chan, L; Devries, S; Chin, K; Scott, GK; Benz, CC; Chen, Y-Y; Waldman, FM; Hwang, ES
MLA Citation
Lal, Aseem, et al. “FOXP3-positive regulatory T lymphocytes and epithelial FOXP3 expression in synchronous normal, ductal carcinoma in situ, and invasive cancer of the breast..” Breast Cancer Res Treat, vol. 139, no. 2, June 2013, pp. 381–90. Pubmed, doi:10.1007/s10549-013-2556-4.
PMID
23712790
Source
pubmed
Published In
Breast Cancer Res Treat
Volume
139
Issue
2
Publish Date
2013
Start Page
381
End Page
390
DOI
10.1007/s10549-013-2556-4

Change in mammographic density with metformin use: A companion study to NCIC study MA.32.

Authors
Wood, ME; Qin, R; Le-Petross, HT; Hwang, ES; Ligibel, JA; Mayer, IA; Marshall, JR; Goodwin, PJ
MLA Citation
Wood, Marie E., et al. “Change in mammographic density with metformin use: A companion study to NCIC study MA.32..” Journal of Clinical Oncology, vol. 31, no. 15, AMER SOC CLINICAL ONCOLOGY, 2013.
Source
wos
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
31
Issue
15
Publish Date
2013

Survival after lumpectomy and mastectomy for early stage invasive breast cancer: the effect of age and hormone receptor status.

BACKGROUND: Randomized clinical trials (RCT) have demonstrated equivalent survival for breast-conserving therapy with radiation (BCT) and mastectomy for early-stage breast cancer. A large, population-based series of women who underwent BCT or mastectomy was studied to observe whether outcomes of RCT were achieved in the general population, and whether survival differed by surgery type when stratified by age and hormone receptor (HR) status. METHODS: Information was obtained regarding all women diagnosed in the state of California with stage I or II breast cancer between 1990 and 2004, who were treated with either BCT or mastectomy and followed for vital status through December 2009. Cox proportional hazards modeling was used to compare overall survival (OS) and disease-specific survival (DSS) between BCT and mastectomy groups. Analyses were stratified by age group (< 50 years and ≥ 50 years) and tumor HR status. RESULTS: A total of 112,154 women fulfilled eligibility criteria. Women undergoing BCT had improved OS and DSS compared with women with mastectomy (adjusted hazard ratio for OS entire cohort = 0.81, 95% confidence interval [CI] = 0.80-0.83). The DSS benefit with BCT compared with mastectomy was greater among women age ≥ 50 with HR-positive disease (hazard ratio = 0.86, 95% CI = 0.82-0.91) than among women age < 50 with HR-negative disease (hazard ratio = 0.88, 95% CI = 0.79-0.98); however, this trend was seen among all subgroups analyzed. CONCLUSIONS: Among patients with early stage breast cancer, BCT was associated with improved DSS. These data provide confidence that BCT remains an effective alternative to mastectomy for early stage disease regardless of age or HR status.

Authors
Hwang, ES; Lichtensztajn, DY; Gomez, SL; Fowble, B; Clarke, CA
MLA Citation
Hwang, E. Shelley, et al. “Survival after lumpectomy and mastectomy for early stage invasive breast cancer: the effect of age and hormone receptor status..” Cancer, vol. 119, no. 7, Apr. 2013, pp. 1402–11. Pubmed, doi:10.1002/cncr.27795.
PMID
23359049
Source
pubmed
Published In
Cancer
Volume
119
Issue
7
Publish Date
2013
Start Page
1402
End Page
1411
DOI
10.1002/cncr.27795

Impact of Race in Prevalence of BRCA Mutations Among Women With Triple-Negative Breast Cancer (TNBC) in a Genetic Counseling Cohort

Authors
Greenup, R; Marcom, PK; McLennan, J; Buchanan, A; King, R; Crawford, B; Chen, Y-Y; Mackey, A; Hwang, ES
MLA Citation
Greenup, Rachel, et al. “Impact of Race in Prevalence of BRCA Mutations Among Women With Triple-Negative Breast Cancer (TNBC) in a Genetic Counseling Cohort.” Annals of Surgical Oncology, vol. 20, SPRINGER, 2013, pp. 17–17.
Source
wos
Published In
Annals of Surgical Oncology
Volume
20
Publish Date
2013
Start Page
17
End Page
17

Multidisciplinary care of patients with early-stage breast cancer.

There is a compelling need for close coordination and integration of multiple specialties in the management of patients with early-stage breast cancer. Optimal patient care and outcomes depend on the sequential and often simultaneous participation and dialogue between specialists in imaging, pathologic and molecular diagnostic and prognostic stratification, and the therapeutic specialties of surgery, radiation oncology, and medical oncology. These are but a few of the various disciplines needed to provide modern, sophisticated management. The essential role for coordinated involvement of the entire health care team in optimal management of patients with early-stage breast cancer is likely to increase further.

Authors
Lyman, GH; Baker, J; Geradts, J; Horton, J; Kimmick, G; Peppercorn, J; Pruitt, S; Scheri, RP; Hwang, ES
MLA Citation
Lyman, Gary H., et al. “Multidisciplinary care of patients with early-stage breast cancer..” Surg Oncol Clin N Am, vol. 22, no. 2, Apr. 2013, pp. 299–317. Pubmed, doi:10.1016/j.soc.2012.12.005.
PMID
23453336
Source
pubmed
Published In
Surg Oncol Clin N Am
Volume
22
Issue
2
Publish Date
2013
Start Page
299
End Page
317
DOI
10.1016/j.soc.2012.12.005

Contralateral Prophylactic Mastectomy for Unilateral Breast Cancer: A Review of the National Comprehensive Cancer Network (NCCN) Database

Authors
Carson, WE; Otteson, RA; Hughes, ME; Neumayer, L; Hwang, ES; Laronga, C; Breslin, T; Chen, SL; Khan, S; Edge, SB; Farrar, WB; Weeks, JC
MLA Citation
Carson, W. E., et al. “Contralateral Prophylactic Mastectomy for Unilateral Breast Cancer: A Review of the National Comprehensive Cancer Network (NCCN) Database.” Annals of Surgical Oncology, vol. 20, SPRINGER, 2013, pp. S10–S10.
Source
wos
Published In
Annals of Surgical Oncology
Volume
20
Publish Date
2013
Start Page
S10
End Page
S10

Outcomes after Mastectomy for Node-positive Breast Cancer: Comparison of Women Treated With and Without Completion Axillary Dissection at NCCN Cancer Centers

Authors
Greenup, RA; Breslin, T; Edge, SB; Hughes, ME; Hwang, ES; Laronga, C; Marcom, P; Moy, B; Otteson, RA; Rugo, H; Wilson, JL; Wong, Y; Weeks, JC
MLA Citation
Greenup, R. A., et al. “Outcomes after Mastectomy for Node-positive Breast Cancer: Comparison of Women Treated With and Without Completion Axillary Dissection at NCCN Cancer Centers.” Annals of Surgical Oncology, vol. 20, SPRINGER, 2013, pp. S9–S9.
Source
wos
Published In
Annals of Surgical Oncology
Volume
20
Publish Date
2013
Start Page
S9
End Page
S9

Abstract P4-14-04: Total skin-sparing mastectomy in BRCA mutation carriers

Authors
Warren, PA; Hwang, ES; Ewing, CA; Alvarado, M; Esserman, LJ
MLA Citation
Warren, Peled A., et al. “Abstract P4-14-04: Total skin-sparing mastectomy in BRCA mutation carriers.” Poster Session Abstracts, American Association for Cancer Research, Dec. 2012. Crossref, doi:10.1158/0008-5472.sabcs12-p4-14-04.
Source
crossref
Published In
Poster Session Abstracts
Publish Date
2012
DOI
10.1158/0008-5472.sabcs12-p4-14-04

Abstract P4-16-07: Selective use of post-mastectomy radiation therapy in the neoadjuvant setting

Authors
Warren, PA; Wang, F; Stover, AC; Rugo, HS; Melisko, ME; Park, JW; Alvarado, M; Ewing, CA; Esserman, LJ; Fowble, B; Hwang, ES
MLA Citation
Warren, Peled A., et al. “Abstract P4-16-07: Selective use of post-mastectomy radiation therapy in the neoadjuvant setting.” Poster Session Abstracts, American Association for Cancer Research, Dec. 2012. Crossref, doi:10.1158/0008-5472.sabcs12-p4-16-07.
Source
crossref
Published In
Poster Session Abstracts
Publish Date
2012
DOI
10.1158/0008-5472.sabcs12-p4-16-07

Cell-extrinsic consequences of epithelial stress: activation of protumorigenic tissue phenotypes.

INTRODUCTION: Tumors are characterized by alterations in the epithelial and stromal compartments, which both contribute to tumor promotion. However, where, when, and how the tumor stroma develops is still poorly understood. We previously demonstrated that DNA damage or telomere malfunction induces an activin A-dependent epithelial stress response that activates cell-intrinsic and cell-extrinsic consequences in mortal, nontumorigenic human mammary epithelial cells (HMECs and vHMECs). Here we show that this epithelial stress response also induces protumorigenic phenotypes in neighboring primary fibroblasts, recapitulating many of the characteristics associated with formation of the tumor stroma (for example, desmoplasia). METHODS: The contribution of extrinsic and intrinsic DNA damage to acquisition of desmoplastic phenotypes was investigated in primary human mammary fibroblasts (HMFs) co-cultured with vHMECs with telomere malfunction (TRF2-vHMEC) or in HMFs directly treated with DNA-damaging agents, respectively. Fibroblast reprogramming was assessed by monitoring increases in levels of selected protumorigenic molecules with quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and immunocytochemistry. Dependence of the induced phenotypes on activin A was evaluated by addition of exogenous activin A or activin A silencing. In vitro findings were validated in vivo, in preinvasive ductal carcinoma in situ (DCIS) lesions by using immunohistochemistry and telomere-specific fluorescent in situ hybridization. RESULTS: HMFs either cocultured with TRF2-vHMEC or directly exposed to exogenous activin A or PGE2 show increased expression of cytokines and growth factors, deposition of extracellular matrix (ECM) proteins, and a shift toward aerobic glycolysis. In turn, these "activated" fibroblasts secrete factors that promote epithelial cell motility. Interestingly, cell-intrinsic DNA damage in HMFs induces some, but not all, of the molecules induced as a consequence of cell-extrinsic DNA damage. The response to cell-extrinsic DNA damage characterized in vitro is recapitulated in vivo in DCIS lesions, which exhibit telomere loss, heightened DNA damage response, and increased activin A and cyclooxygenase-2 expression. These lesions are surrounded by a stroma characterized by increased expression of α smooth muscle actin and endothelial and immune cell infiltration. CONCLUSIONS: Thus, synergy between stromal and epithelial interactions, even at the initiating stages of carcinogenesis, appears necessary for the acquisition of malignancy and provides novel insights into where, when, and how the tumor stroma develops, allowing new therapeutic strategies.

Authors
Fordyce, CA; Patten, KT; Fessenden, TB; DeFilippis, R; Hwang, ES; Zhao, J; Tlsty, TD
MLA Citation
Fordyce, Colleen A., et al. “Cell-extrinsic consequences of epithelial stress: activation of protumorigenic tissue phenotypes..” Breast Cancer Res, vol. 14, no. 6, Dec. 2012. Pubmed, doi:10.1186/bcr3368.
PMID
23216814
Source
pubmed
Published In
Breast Cancer Res
Volume
14
Issue
6
Publish Date
2012
Start Page
R155
DOI
10.1186/bcr3368

Paget's disease of the breast masquerading as squamous cell carcinoma on cytology: a case report.

Paget's disease is an uncommon manifestation of breast carcinoma occurring in 1-2% of female patients with breast cancer. Here, we present a case of Paget's disease of the breast, which was initially interpreted as squamous cell carcinoma on cytology. This case report raises two issues. First, histological and cytological specimens of Paget's disease show a mixed population of epithelial cells including squamous cells with reactive changes and malignant glandular cells. In the current case, a mixed population of atypical keratinizing and nonkeratinizing epithelial cells was initially interpreted as squamous cell carcinoma of cutaneous origin. The marked reactive changes in the squamous epithelium involved by Paget's disease should be recognized. Second, this case is an unusual clinical presentation for Paget's disease of the breast as the nipple-areolar complex and underlying breast tissue were surgically absent at the time of diagnosis. Clinical suspicion, along with an awareness of the cytologic features and clinical presentation of Paget's disease, can help in reaching the correct diagnosis in a timely fashion.

Authors
Vohra, P; Ljung, B-ME; Miller, TR; Hwang, E-S; van Zante, A
MLA Citation
Vohra, Poonam, et al. “Paget's disease of the breast masquerading as squamous cell carcinoma on cytology: a case report..” Diagn Cytopathol, vol. 40, no. 11, Nov. 2012, pp. 1015–18. Pubmed, doi:10.1002/dc.21712.
PMID
21548119
Source
pubmed
Published In
Diagn Cytopathol
Volume
40
Issue
11
Publish Date
2012
Start Page
1015
End Page
1018
DOI
10.1002/dc.21712

Lobular histology and response to neoadjuvant chemotherapy in invasive breast cancer.

Invasive lobular carcinoma (ILC) has been reported to be less responsive to neoadjuvant chemotherapy (NAC) than invasive ductal carcinoma (IDC). We sought to determine whether ILC histology indeed predicts poor response to NAC by analyzing tumor characteristics such as protein expression, gene expression, and imaging features, and by comparing NAC response rates to those seen in IDC after adjustment for these factors. We combined datasets from two large prospective NAC trials, including in total 676 patients, of which 75 were of lobular histology. Eligible patients had tumors ≥3 cm in diameter or pathologic documentation of positive nodes, and underwent serial biopsies, expression microarray analysis, and MRI imaging. We compared pathologic complete response (pCR) rates and breast conservation surgery (BCS) rates between ILC and IDC, adjusted for clinicopathologic factors. On univariate analysis, ILCs were significantly less likely to have a pCR after NAC than IDCs (11 vs. 25 %, p = 0.01). However, the known differences in tumor characteristics between the two histologic types, including hormone receptor (HR) status, HER2 status, histological grade, and p53 expression, accounted for this difference with the lowest pCR rates among HR+/HER2- tumors in both ILC and IDC (7 and 5 %, respectively). ILC which were HR- and/or HER2+ had a pCR rate of 25 %. Expression subtyping, particularly the NKI 70-gene signature, was correlated with pCR, although the small numbers of ILC in each group precluded significant associations. BCS rate did not differ between IDC and ILC after adjusting for molecular characteristics. We conclude that ILC represents a heterogeneous group of tumors which are less responsive to NAC than IDC. However, this difference is explained by differences in molecular characteristics, particularly HR and HER2, and independent of lobular histology.

Authors
Lips, EH; Mukhtar, RA; Yau, C; de Ronde, JJ; Livasy, C; Carey, LA; Loo, CE; Vrancken-Peeters, M-JTFD; Sonke, GS; Berry, DA; Van't Veer, LJ; Esserman, LJ; Wesseling, J; Rodenhuis, S; Shelley Hwang, E; I-SPY TRIAL Investigators,
MLA Citation
Lips, Esther H., et al. “Lobular histology and response to neoadjuvant chemotherapy in invasive breast cancer..” Breast Cancer Res Treat, vol. 136, no. 1, Nov. 2012, pp. 35–43. Pubmed, doi:10.1007/s10549-012-2233-z.
PMID
22961065
Source
pubmed
Published In
Breast Cancer Res Treat
Volume
136
Issue
1
Publish Date
2012
Start Page
35
End Page
43
DOI
10.1007/s10549-012-2233-z

Outcomes after total skin-sparing mastectomy and immediate reconstruction in 657 breasts.

BACKGROUND: Total skin-sparing mastectomy (TSSM), a technique comprising removal of all breast and nipple tissue while preserving the entire skin envelope, is increasingly offered to women for therapeutic and prophylactic indications. However, standard use of the procedure remains controversial as a result oft concerns regarding oncologic safety and risk of complications. METHODS: Outcomes from a prospectively maintained database of patients undergoing TSSM and immediate breast reconstruction from 2001 to 2010 were reviewed. Outcome measures included postoperative complications, tumor involvement of the nipple-areolar complex (NAC) on pathologic analysis, and cancer recurrence. RESULTS: TSSM was performed on 657 breasts in 428 patients. Indications included in situ cancer [111 breasts (16.9%)], invasive cancer [301 breasts (45.8%)], and prophylactic risk-reduction [245 breasts (37.3%)]. A total of 210 patients (49%) had neoadjuvant chemotherapy, 78 (18.2%) had adjuvant chemotherapy, and 114 (26.7%) had postmastectomy radiotherapy. Nipple tissue contained in situ cancer in 11 breasts (1.7%) and invasive cancer in 9 breasts (1.4%); management included repeat excision (7 cases), NAC removal (9 cases), or radiotherapy without further excision (4 cases). Ischemic complications included 13 cases (2%) of partial nipple loss, 10 cases (1.5%) of complete nipple loss, and 78 cases (11.9%) of skin flap necrosis. Overall locoregional recurrence rate was 2% (median follow-up 28 months), with a 2.4% rate observed in the subset of patients with at least 3 years' follow-up (median 45 months). No NAC skin recurrences were observed. CONCLUSIONS: In this large, high-risk cohort, TSSM was associated with low rates of NAC complications, nipple involvement, and locoregional recurrence.

Authors
Warren Peled, A; Foster, RD; Stover, AC; Itakura, K; Ewing, CA; Alvarado, M; Hwang, ES; Esserman, LJ
MLA Citation
Warren Peled, Anne, et al. “Outcomes after total skin-sparing mastectomy and immediate reconstruction in 657 breasts..” Ann Surg Oncol, vol. 19, no. 11, Oct. 2012, pp. 3402–09. Pubmed, doi:10.1245/s10434-012-2362-y.
PMID
22526909
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
19
Issue
11
Publish Date
2012
Start Page
3402
End Page
3409
DOI
10.1245/s10434-012-2362-y

Increasing the time to expander-implant exchange after postmastectomy radiation therapy reduces expander-implant failure.

BACKGROUND: Increased rates of complications can occur when postmastectomy radiation therapy is required after immediate expander-implant breast reconstruction. The sequence and timing of tissue expansion and implant exchange with regard to postmastectomy radiation therapy may impact complication rates. METHODS: A prospectively maintained database of patients undergoing mastectomy and immediate reconstruction was queried for patients who underwent postmastectomy radiation therapy. The authors' protocol is to complete tissue expansion before radiation, irradiate the fully inflated expander, and then perform expander-implant exchange. Starting in 2009, the authors refined their protocol by increasing the time interval between completion of radiation therapy and expander-implant exchange from 3 months to 6 months as a strategy to reduce surgical complications. For analysis, patients were divided into two cohorts based on whether expander-implant exchange was performed less than 6 months or more than 6 months after radiation. The primary outcome was expander-implant failure, defined as device removal without concurrent replacement. RESULTS: Eighty-eight patients met selection criteria; 49 (55.7 percent) had expander-implant exchange within 6 months of completing radiation therapy (mean, 3.4 months; range, 1.2 to 5.8 months), and the rest had at least a 6-month interval (mean, 8.6 months; range, 6.1 to 17.1 months). Risk factors for postoperative complications were equivalent between cohorts. Overall expander-implant failure was 15.9 percent; failure was significantly higher in the cohort with less than 6 months' time before exchange (22.4 percent versus 7.7 percent, p = 0.036). CONCLUSION: Delaying expander-implant exchange for at least 6 months after the completion of postmastectomy radiation therapy can significantly reduce expander-implant failure.

Authors
Peled, AW; Foster, RD; Esserman, LJ; Park, CC; Hwang, ES; Fowble, B
MLA Citation
Peled, Anne Warren, et al. “Increasing the time to expander-implant exchange after postmastectomy radiation therapy reduces expander-implant failure..” Plast Reconstr Surg, vol. 130, no. 3, Sept. 2012, pp. 503–09. Pubmed, doi:10.1097/PRS.0b013e31825dbf15.
PMID
22929235
Source
pubmed
Published In
Plast Reconstr Surg
Volume
130
Issue
3
Publish Date
2012
Start Page
503
End Page
509
DOI
10.1097/PRS.0b013e31825dbf15

377 Extra-cellular Matrix Stiffness and Immune Cells Infiltrate Are Associated With Breast Tumor Phenotype

Authors
Acerbi, I; Zheng, SY; Ruffell, B; Au, A; Shi, Q; Liphardt, JT; Coussens, LM; Chen, YY; Hwang, ES; Weaver, VM
MLA Citation
Acerbi, I., et al. “377 Extra-cellular Matrix Stiffness and Immune Cells Infiltrate Are Associated With Breast Tumor Phenotype.” European Journal of Cancer, vol. 48, Elsevier BV, 2012, pp. S91–S91. Crossref, doi:10.1016/s0959-8049(12)71063-8.
Source
crossref
Published In
European Journal of Cancer
Volume
48
Publish Date
2012
Start Page
S91
End Page
S91
DOI
10.1016/s0959-8049(12)71063-8

Role of postmastectomy radiation after neoadjuvant chemotherapy in stage II-III breast cancer.

PURPOSE: To identify a cohort of women treated with neoadjuvant chemotherapy and mastectomy for whom postmastectomy radiation therapy (PMRT) may be omitted according to the projected risk of local-regional failure (LRF). METHODS AND MATERIALS: Seven breast cancer physicians from the University of California cancer centers created 14 hypothetical clinical case scenarios, identified, reviewed, and abstracted the available literature (MEDLINE and Cochrane databases), and formulated evidence tables with endpoints of LRF, disease-free survival, and overall survival. Using the American College of Radiology appropriateness criteria methodology, appropriateness ratings for postmastectomy radiation were assigned for each scenario. Finally, an overall summary risk assessment table was developed. RESULTS: Of 24 sources identified, 23 were retrospective studies from single institutions. Consensus on the appropriateness rating, defined as 80% agreement in a category, was achieved for 86% of the cases. Distinct LRF risk categories emerged. Clinical stage II (T1-2N0-1) patients, aged >40 years, estrogen receptor-positive subtype, with pathologic complete response or 0-3 positive nodes without lymphovascular invasion or extracapsular extension, were identified as having ≤ 10% risk of LRF without radiation. Limited data support stage IIIA patients with pathologic complete response as being low risk. CONCLUSIONS: In the absence of randomized trial results, existing data can be used to guide the use of PMRT in the neoadjuvant chemotherapy setting. Using available studies to inform appropriateness ratings for clinical scenarios, we found a high concordance of treatment recommendations for PMRT and were able to identify a cohort of women with a low risk of LRF without radiation. These low-risk patients will form the basis for future planned studies within the University of California Athena Breast Health Network.

Authors
Fowble, BL; Einck, JP; Kim, DN; McCloskey, S; Mayadev, J; Yashar, C; Chen, SL; Hwang, ES; Athena Breast Health Network,
MLA Citation
Fowble, Barbara L., et al. “Role of postmastectomy radiation after neoadjuvant chemotherapy in stage II-III breast cancer..” Int J Radiat Oncol Biol Phys, vol. 83, no. 2, June 2012, pp. 494–503. Pubmed, doi:10.1016/j.ijrobp.2012.01.068.
PMID
22579377
Source
pubmed
Published In
Int J Radiat Oncol Biol Phys
Volume
83
Issue
2
Publish Date
2012
Start Page
494
End Page
503
DOI
10.1016/j.ijrobp.2012.01.068

Reframing treatment for ductal carcinoma in situ: could less be more?

Authors
Hwang, ES; Nelson, H
MLA Citation
Hwang, E. Shelley, and Heidi Nelson. “Reframing treatment for ductal carcinoma in situ: could less be more?.” Bull Am Coll Surg, vol. 97, no. 6, June 2012, pp. 50–51.
PMID
22745990
Source
pubmed
Published In
Bulletin of the American College of Surgeons
Volume
97
Issue
6
Publish Date
2012
Start Page
50
End Page
51

Evaluating the feasibility of extended partial mastectomy and immediate reduction mammoplasty reconstruction as an alternative to mastectomy.

OBJECTIVES: To assess the efficacy of using concurrent partial mastectomy and reduction mammoplasty for resection of a wide range of tumor sizes and compare oncologic outcomes and postoperative complications on the basis of tumor size. BACKGROUND: Although tumor size greater than 4 cm has been considered an indication for undergoing a mastectomy, this dictum may not apply in women with breast hypertrophy, where the ratio of tumor size to breast size may still permit breast conservation. We wished to evaluate whether an approach combining partial mastectomy with reduction mammoplasty could provide a safe oncologic procedure with immediate breast reconstruction that could technically be applied even for large (>4 cm) lesions. METHODS: A retrospective review of all patients undergoing partial mastectomy and concurrent reduction mammoplasty performed at our institution from 2000 to 2009. Clinical characteristics at presentation, pathologic data, and follow-up data were collected and analyzed. RESULTS: Eighty-five consecutive simultaneous partial mastectomy/reduction mammoplasty procedures were performed in 79 patients. Average tumor size was 2.8 cm for ductal carcinoma in situ (0.05-17.0 cm), 2.4 cm for invasive ductal carcinoma (IDC) (0.2-8.9 cm), 3.5 cm for lobular carcinoma (1.6-8.0 cm), and 5.7 cm for phyllodes tumors (3.7-7.6 cm). Twenty-five of 85 tumors (29.4%) were larger than 4 cm. Distribution for stage 0, I, II, III, and IV disease was 15, 12, 35, 19, and 2 tumors respectively, with an additional 2 phyllodes tumors. Median follow-up was 39 months (10-130 months). Seventy-five patients (94.9%) achieved successful breast conservation, whereas 4 patients (5.1%) went on to completion mastectomy. Thirteen patients (16.4%) required 1 reexcision to achieve clear margins, and 2 (2.5%) required multiple reexcisions. Two patients had a local recurrence during the follow-up period, one of whom underwent reexcision and the other underwent mastectomy. The overall complication rate was 14.1%, which included 4 major complications (4.7%) requiring an unplanned return to the operating room and need for hospital readmission, and 8 minor wound-related complications (9.4%). Neither recurrence nor complication rates were increased in patients with tumors greater than 4 cm when compared with tumors less than or equal to 4 cm. CONCLUSIONS: A partial mastectomy with concurrent reduction mammoplasty technique is a viable option for breast conservation even for larger tumors, combining a safe oncologic procedure with excellent cosmesis. A combined effort between breast surgeons and reconstructive surgeons has a high probability of success with low recurrence rates. In carefully selected patients, this approach may be preferable to mastecomy and breast reconstruction, particularly when postmastectomy radiation therapy is anticipated.

Authors
Chang, EI; Peled, AW; Foster, RD; Lin, C; Zeidler, KR; Ewing, CA; Alvarado, M; Hwang, ES; Esserman, LJ
MLA Citation
Chang, Edward I., et al. “Evaluating the feasibility of extended partial mastectomy and immediate reduction mammoplasty reconstruction as an alternative to mastectomy..” Ann Surg, vol. 255, no. 6, June 2012, pp. 1151–57. Pubmed, doi:10.1097/SLA.0b013e31824f9769.
PMID
22470069
Source
pubmed
Published In
Ann Surg
Volume
255
Issue
6
Publish Date
2012
Start Page
1151
End Page
1157
DOI
10.1097/SLA.0b013e31824f9769

The effects of acellular dermal matrix in expander-implant breast reconstruction after total skin-sparing mastectomy: results of a prospective practice improvement study.

BACKGROUND: Neither outcome after total skin-sparing mastectomy and expander-implant reconstruction using acellular dermal matrix nor a strategy for optimal acellular dermal matrix selection criteria has been well described. METHODS: Prospective review of three patient cohorts undergoing total skin-sparing mastectomy with preservation of the nipple-areola complex and immediate expander-implant reconstruction from 2006 to 2010 was performed. Cohort 1 (no acellular dermal matrix) comprised 90 cases in which acellular dermal matrix was not used. Cohort 2 (consecutive acellular dermal matrix) included the next 100 consecutive cases, which all received acellular dermal matrix. Cohort 3 (selective acellular dermal matrix) consisted of the next 260 cases, in which acellular dermal matrix was selectively used based on mastectomy skin flap thickness. Complication rates were compared using chi-square analysis. RESULTS: The study included 450 cases in 288 patients. Mean follow-up was 25.5 months. Infection occurred in 27.8 percent of the no-acellular dermal matrix cases, 20 percent of the consecutive cases, and 15.8 percent of the selective cases (p = 0.04). Unplanned return to the operating room was required in 23.3, 11, and 10 percent of cases, respectively (p = 0.004). Expander-implant loss occurred in 17.8, 7, and 5 percent of cases, respectively (p = 0.001). Additional analysis of the odds ratios of developing complications after postmastectomy radiation therapy demonstrated a specific protective benefit of acellular dermal matrix in irradiated patients. CONCLUSIONS: Acellular dermal matrix use in expander-implant reconstruction after total skin-sparing mastectomy reduced major postoperative complications in this study. Maximal benefit is achieved with selected use in patients with thin mastectomy skin flaps and those receiving radiation therapy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Authors
Peled, AW; Foster, RD; Garwood, ER; Moore, DH; Ewing, CA; Alvarado, M; Hwang, ES; Esserman, LJ
MLA Citation
Peled, Anne Warren, et al. “The effects of acellular dermal matrix in expander-implant breast reconstruction after total skin-sparing mastectomy: results of a prospective practice improvement study..” Plast Reconstr Surg, vol. 129, no. 6, June 2012, pp. 901e-908e. Pubmed, doi:10.1097/PRS.0b013e31824ec447.
PMID
22634688
Source
pubmed
Published In
Plast Reconstr Surg
Volume
129
Issue
6
Publish Date
2012
Start Page
901e
End Page
908e
DOI
10.1097/PRS.0b013e31824ec447

Long-term reconstructive outcomes after expander-implant breast reconstruction with serious infectious or wound-healing complications.

INTRODUCTION: Immediate expander-implant breast reconstruction has been associated with postoperative complications, including infection and wound-healing problems. In extreme cases, these issues can lead to expander-implant loss. Little is known about the long-term reconstructive outcomes for patients who develop major complications threatening their expander-implant reconstructions. METHODS: A review of all patients who underwent mastectomy and immediate expander-implant reconstruction at University of California, San Francisco (UCSF) from 2005 to 2007 was performed. A prospective database was queried for patients who developed a major postoperative complication related to infection or wound-healing problems requiring unplanned operative intervention. Only patients who had a minimum of 3 years' follow-up were included in the study. RESULTS: Twenty-nine patients were identified who met study criteria. Mean follow-up time was 52.5 months (range, 41-71 months). Six of the 29 (20.7%) patients had received prior breast irradiation, and 9 patients (31%) underwent postoperative radiation therapy. Reasons for unplanned return to the operating room included infection (n = 11, 37.9%), expander-implant exposure (n = 5, 17.2%), nonhealing wounds without underlying exposure (n = 3, 1.3%), or >1 of these indications (n = 10, 34.5%). Unplanned operative intervention (such as wound debridement or expander-implant exchange or removal) was required once in 10 patients (34.5%), twice in 10 patients (34.5%), 3 times in 4 patients (13.8%), 4 times in 1 patient (3.4%), and 5 or greater times in 4 patients (13.8%). At the conclusion of all operative interventions, 15 patients (51.7%) had successful breast reconstruction using an expander-implant technique. Five additional patients (17.3%) ultimately achieved successful salvage reconstruction with either a transverse rectus abdominis myocutaneous (TRAM) or deep inferior epigastric perforator (DIEP) flap. Nine patients (31%) did not have successful breast reconstruction. Of these 9 patients, 5 elected to abandon reconstructive efforts after 1 unplanned return to the operating room for expander-implant removal, whereas the rest underwent at least 1 attempt at expander-implant salvage, with the overall rate of final successful reconstruction after attempt at salvage 83.3% (20 of 24 patients). CONCLUSIONS: Even when unplanned operative intervention is required to address postoperative wound-healing or infectious complications after expander-implant reconstruction, the majority of patients can achieve successful reconstructive outcomes at long-term follow-up, including those patients requiring multiple operative interventions to treat their complication.

Authors
Peled, AW; Stover, AC; Foster, RD; McGrath, MH; Hwang, ES
MLA Citation
Peled, Anne Warren, et al. “Long-term reconstructive outcomes after expander-implant breast reconstruction with serious infectious or wound-healing complications..” Ann Plast Surg, vol. 68, no. 4, Apr. 2012, pp. 369–73. Pubmed, doi:10.1097/SAP.0b013e31823aee67.
PMID
22421481
Source
pubmed
Published In
Ann Plast Surg
Volume
68
Issue
4
Publish Date
2012
Start Page
369
End Page
373
DOI
10.1097/SAP.0b013e31823aee67

Leukocyte composition of human breast cancer.

Retrospective clinical studies have used immune-based biomarkers, alone or in combination, to predict survival outcomes for women with breast cancer (BC); however, the limitations inherent to immunohistochemical analyses prevent comprehensive descriptions of leukocytic infiltrates, as well as evaluation of the functional state of leukocytes in BC stroma. To more fully evaluate this complexity, and to gain insight into immune responses after chemotherapy (CTX), we prospectively evaluated tumor and nonadjacent normal breast tissue from women with BC, who either had or had not received neoadjuvant CTX before surgery. Tissues were evaluated by polychromatic flow cytometry in combination with confocal immunofluorescence and immunohistochemical analysis of tissue sections. These studies revealed that activated T lymphocytes predominate in tumor tissue, whereas myeloid lineage cells are more prominant in "normal" breast tissue. Notably, residual tumors from an unselected group of BC patients treated with neoadjuvant CTX contained increased percentages of infiltrating myeloid cells, accompanied by an increased CD8/CD4 T-cell ratio and higher numbers of granzyme B-expressing cells, compared with tumors removed from patients treated primarily by surgery alone. These data provide an initial evaluation of differences in the immune microenvironment of BC compared with nonadjacent normal tissue and reveal the degree to which CTX may alter the complexity and presence of selective subsets of immune cells in tumors previously treated in the neoadjuvant setting.

Authors
Ruffell, B; Au, A; Rugo, HS; Esserman, LJ; Hwang, ES; Coussens, LM
MLA Citation
Ruffell, Brian, et al. “Leukocyte composition of human breast cancer..” Proc Natl Acad Sci U S A, vol. 109, no. 8, Feb. 2012, pp. 2796–801. Pubmed, doi:10.1073/pnas.1104303108.
PMID
21825174
Source
pubmed
Published In
Proc Natl Acad Sci U S A
Volume
109
Issue
8
Publish Date
2012
Start Page
2796
End Page
2801
DOI
10.1073/pnas.1104303108

Inhibiting the palmitoylation/depalmitoylation cycle selectively reduces the growth of hematopoietic cells expressing oncogenic Nras.

The palmitoylation/depalmitoylation cycle of posttranslational processing is a potential therapeutic target for selectively inhibiting the growth of hematologic cancers with somatic NRAS mutations. To investigate this question at the single-cell level, we constructed murine stem cell virus vectors and assayed the growth of myeloid progenitors. Whereas cells expressing oncogenic N-Ras(G12D) formed cytokine-independent colonies and were hypersensitive to GM-CSF, mutations within the N-Ras hypervariable region induced N-Ras mislocalization and attenuated aberrant progenitor growth. Exposing transduced hematopoietic cells and bone marrow from Nras and Kras mutant mice to the acyl protein thioesterase inhibitor palmostatin B had similar effects on protein localization and colony growth. Importantly, palmostatin B-mediated inhibition was selective for Nras mutant cells, and we mapped this activity to the hypervariable region. These data support the clinical development of depalmitoylation inhibitors as a novel class of rational therapeutics in hematologic malignancies with NRAS mutations.

Authors
Xu, J; Hedberg, C; Dekker, FJ; Li, Q; Haigis, KM; Hwang, E; Waldmann, H; Shannon, K
MLA Citation
Xu, Jin, et al. “Inhibiting the palmitoylation/depalmitoylation cycle selectively reduces the growth of hematopoietic cells expressing oncogenic Nras..” Blood, vol. 119, no. 4, Jan. 2012, pp. 1032–35. Pubmed, doi:10.1182/blood-2011-06-358960.
PMID
22144181
Source
pubmed
Published In
Blood
Volume
119
Issue
4
Publish Date
2012
Start Page
1032
End Page
1035
DOI
10.1182/blood-2011-06-358960

Adjuvant hormonal therapy use among women with ductal carcinoma in situ.

OBJECTIVE: In the absence of consistent guidelines for the use of adjuvant hormonal therapy (HT) in treating ductal carcinoma in situ (DCIS), our purpose was to explore a variety of factors associated with discussion, use, and discontinuation of this therapy for DCIS, including patient, tumor, and treatment-related characteristics and physician-patient communication factors. METHODS: We identified women from eight California Cancer Registry regions diagnosed with DCIS from 2002 through 2005, aged ≥18 years, of Latina or non-Latina white race/ethnicity. A total of 744 women were interviewed an average of 24 months postdiagnosis about whether they had (1) discussed with a physician, (2) used, and (3) discontinued adjuvant HT. RESULTS: Although 83% of women discussed adjuvant HT with a physician, 47% used adjuvant HT, and 23% of users reported discontinuation by a median of 11 months. In multivariable adjusted analyses, Latina Spanish speakers were less likely than white women to discuss therapy (odds ratio [OR] 0.36, 95% confidence interval [CI] 0.18-0.69) and more likely to discontinue therapy (OR 2.67, 95% CI 1.05-6.81). Seeing an oncologist for follow-up care was associated with discussion (OR 5.10, 95% CI 3.14-8.28) and use of therapy (OR 4.20, 95% CI 2.05-8.61). Similarly, physician recommendation that treatment was necessary vs. optional was positively associated with use (OR 11.2, 95% CI 6.50-19.4) and inversely associated with discontinuation (OR 0.38, 95% CI 0.19-0.73). CONCLUSIONS: Physician recommendation is an important factor associated with use and discontinuation of adjuvant HT for DCIS. Differences in discussion and discontinuation of therapy according to patient characteristics, particularly ethnicity/language, suggest challenges to physician-patient communication about adjuvant HT across a language barrier.

Authors
Livaudais, JC; Hwang, ES; Karliner, L; Nápoles, A; Stewart, S; Bloom, J; Kaplan, CP
MLA Citation
Livaudais, Jennifer C., et al. “Adjuvant hormonal therapy use among women with ductal carcinoma in situ..” J Womens Health (Larchmt), vol. 21, no. 1, Jan. 2012, pp. 35–42. Pubmed, doi:10.1089/jwh.2011.2773.
PMID
21902542
Source
pubmed
Published In
J Womens Health (Larchmt)
Volume
21
Issue
1
Publish Date
2012
Start Page
35
End Page
42
DOI
10.1089/jwh.2011.2773

Neoadjuvant endocrine therapy in the treatment of early-stage breast cancer

Endocrine therapy is the first targeted biologic therapy to be used in breast cancer treatment and was initially conceived in 1895. Based on the observation that lactation led to a cancer-like ductal epithelial proliferation in cattle and that castration of these cattle led to fatty degeneration of this epithelium, George Thomas Beatson, a Scottish surgeon, hypothesized that bilateral oophorectomy might benefit women with advanced breast cancer. He tested this hypothesis in Glasgow Cancer Hospital on a 33-year-old woman with recurrent soft tissue, axillary, and chest wall disease. Beatson described the case in the Lancet in 1896, reporting significant regression of the patient's cancer after which she survived for another 4 years. Beatson's initial report and subsequent reasoning in a 1901 edition of the Lancet that, "we must look in the female to the ovaries as the seat of the exciting cause of carcinoma, certainly of the mamma.." led to the adoption of oophorectomy for breast cancer. Although oophorectomy was effective in only about a third of women with advanced breast cancer, it became the standard of care for patients with limited adjuvant treatment options. This chapter provides an overview of available endocrine options for neoadjuvant therapy of breast cancer. © 2011 Springer Science + Business Media.

Authors
Hwang, ES; Jelin, E
MLA Citation
Hwang, E. S., and E. Jelin. “Neoadjuvant endocrine therapy in the treatment of early-stage breast cancer.” Breast Surgical Techniques and Interdisciplinary Management, 2011, pp. 717–29. Scopus, doi:10.1007/978-1-4419-6076-4_59.
Source
scopus
Publish Date
2011
Start Page
717
End Page
729
DOI
10.1007/978-1-4419-6076-4_59

Outcome of long term active surveillance for estrogen receptor-positive ductal carcinoma in situ.

INTRODUCTION: An option for active surveillance is not currently offered to patients with ductal carcinoma in situ (DCIS); however a small number of women decline standard surgical treatment for noninvasive cancer. The purpose of this study was to assess outcomes in a cohort of 14 well-informed women who elected non-surgical active surveillance with endocrine treatment alone for estrogen receptor-positive DCIS. METHODS: Retrospective review of 14 women, 12 of whom were enrolled in an IRB-approved single-arm study of 3 months of neoadjuvant endocrine therapy prior to definitive surgical management. The patients in this report withdrew from the parent study opting instead for active surveillance with endocrine treatment and imaging. RESULTS: 8 women had surgery at a median follow up of 28.3 months (range 10.1-70 months), 5 had stage I IDC at surgical excision, and 3 had DCIS alone. 6 women remain on surveillance without evidence of invasive disease for a median of 31.8 months (range 11.8-80.8 months). CONCLUSION: Long-term active surveillance for DCIS is feasible in a well-informed patient population, but is associated with risk of invasive cancer at surgical excision.

Authors
Meyerson, AF; Lessing, JN; Itakura, K; Hylton, NM; Wolverton, DE; Joe, BN; Esserman, LJ; Hwang, ES
MLA Citation
Meyerson, Anna F., et al. “Outcome of long term active surveillance for estrogen receptor-positive ductal carcinoma in situ..” Breast, vol. 20, no. 6, Dec. 2011, pp. 529–33. Pubmed, doi:10.1016/j.breast.2011.06.001.
PMID
21843942
Source
pubmed
Published In
Breast
Volume
20
Issue
6
Publish Date
2011
Start Page
529
End Page
533
DOI
10.1016/j.breast.2011.06.001

Genomic alterations and phenotype of large compared to small high-grade ductal carcinoma in situ.

A clinically distinct subgroup of pure ductal carcinoma in situ presents as an extensive, high-grade lesion, which nevertheless lacks invasion. We sought to evaluate differences between those ductal carcinomas in situ presenting as large versus small lesions while controlling for high-grade, to determine whether there exist phenotypic and genetic differences between the 2 groups. Fifty-two cases of pure high-grade ductal carcinomas in situ were collected retrospectively, consisting of 27 large (>40 mm) and 25 small (<15 mm) cases. The 2 groups were compared based on genomic copy number assessed by array-based comparative genomic hybridization and by phenotype determined by immunohistochemistry for estrogen receptor, progesterone receptor, Ki-67, p53, cyclin D1, p16, cyclooxygenase 2, human epidermal growth factor receptor 2, and CD68. Large lesions presented at a younger age, with lower incidence of comedonecrosis and periductal macrophage response. Larger lesions also had significantly lower estrogen receptor expression, lower cyclin D1 expression, and lower Ki-67 index. The subset of 9 large palpable tumors had significantly lower p16/cyclooxygenase 2 expression and lower Ki-67 index compared to nonpalpable tumors. Genomically, larger lesions had fewer break points, fewer amplifications, and decreased copy number gains involving chromosome 8q and chromosome 20q when compared to the small lesions. Among pure high-grade tumors, small and large groups show specific genomic and phenotypic differences. Interestingly, larger tumors showed some molecular features associated with better prognosis. A more thorough evaluation of these differences could help identify the likelihood of recurrence or progression for in situ lesions.

Authors
Hwang, ES; Lal, A; Chen, Y-Y; DeVries, S; Swain, R; Anderson, J; Roy, R; Waldman, FM
MLA Citation
Hwang, E. Shelley, et al. “Genomic alterations and phenotype of large compared to small high-grade ductal carcinoma in situ..” Hum Pathol, vol. 42, no. 10, Oct. 2011, pp. 1467–75. Pubmed, doi:10.1016/j.humpath.2011.01.002.
PMID
21496874
Source
pubmed
Published In
Hum Pathol
Volume
42
Issue
10
Publish Date
2011
Start Page
1467
End Page
1475
DOI
10.1016/j.humpath.2011.01.002

The effect of system-level access factors on receipt of reconstruction among Latina and white women with DCIS.

Treatment decisions associated with ductal carcinoma in situ (DCIS), including the decision to undergo breast reconstruction, may be more problematic for Latinas due to access and language issues. To help understand the factors that influence patients' receipt of reconstruction following mastectomy for DCIS, we conducted a population-based study of English- and Spanish-speaking Latina and non-Latina white women from 35 California counties. The objectives of this study were to identify the role of ethnicity and language in the receipt of reconstruction, the relationship between system-level factors and the receipt of reconstruction, and women's reasons for not undergoing reconstruction. Women aged 18 and older, who self-identified as Latina or non-Latino white and were diagnosed with DCIS between 2002 and 2005 were selected from eight California Cancer Registry (CCR) regions encompassing 35 counties. Approximately 24 months after diagnosis, they were surveyed about their DCIS treatment decisions. Survey data were merged with CCR records to obtain tumor and treatment data. The survey was successfully completed by 745 women, 239 of whom had a mastectomy and represent the sample included in this study. Whites had a higher completion rate than Latinas (67 and 55%, respectively). Analysis included descriptive statistics and logistic regression modeling. Mean age was 54 years. A greater proportion of whites had reconstruction (72%) compared to English-speaking Latinas (69%) and Spanish-speaking Latinas (40%). Multivariate analysis showed that women who were aged 65 and older, unemployed, and had a lower ratio of plastic surgeons in their county were less likely to have reconstructive surgery after mastectomy. The most frequent reasons mentioned not to receive reconstruction included lack of importance and desire to avoid additional surgery. Although ethnic/language differences in treatment selection were observed, multivariable analysis suggests that these differences could be explained by differential employment levels and geographic availability of plastic surgeons.

Authors
Kaplan, CP; Karliner, LS; Hwang, ES; Bloom, J; Stewart, S; Nickleach, D; Quinn, J; Thrasher, A; Nápoles, AM
MLA Citation
Kaplan, Celia Patricia, et al. “The effect of system-level access factors on receipt of reconstruction among Latina and white women with DCIS..” Breast Cancer Res Treat, vol. 129, no. 3, Oct. 2011, pp. 909–17. Pubmed, doi:10.1007/s10549-011-1524-0.
PMID
21533531
Source
pubmed
Published In
Breast Cancer Res Treat
Volume
129
Issue
3
Publish Date
2011
Start Page
909
End Page
917
DOI
10.1007/s10549-011-1524-0

Characterizing the impact of 25 years of DCIS treatment.

The significant increase in the detection and treatment of ductal carcinoma in situ (DCIS) since the introduction of screening mammography has not been accompanied by the anticipated reduction in invasive breast cancer (IBC) incidence. The prevalence of DCIS requires a reexamination of the population level effects of detecting and treating DCIS. To further our understanding of the possible impact of DCIS diagnosis and treatment on IBC incidence in the U.S., we simulated breast cancer incidence over 25 years under various assumptions regarding the baseline incidence of IBC and the progression of DCIS to IBC. The simulations demonstrate a tradeoff between the expected increased incidence of IBC absent any DCIS detection and treatment and the rate of progression of DCIS to IBC. Our analyses indicate that a high progression of DCIS to IBC implies a significant increase in incidence of IBC over what is observed had we not detected and treated DCIS. Conversely, if we assume that there would not have been a significant increase over and above the observed incidence evident in SEER, then our model indicates that the rate of DCIS progression to clinically significant IBC is low. Given the tradeoff illustrated by our model, we must reevaluate the assumption that DCIS is a short-term obligate precursor of invasive cancer and instead focus on further exploration of the true natural history of DCIS.

Authors
Ozanne, EM; Shieh, Y; Barnes, J; Bouzan, C; Hwang, ES; Esserman, LJ
MLA Citation
Ozanne, Elissa M., et al. “Characterizing the impact of 25 years of DCIS treatment..” Breast Cancer Res Treat, vol. 129, no. 1, Aug. 2011, pp. 165–73. Pubmed, doi:10.1007/s10549-011-1430-5.
PMID
21390494
Source
pubmed
Published In
Breast Cancer Res Treat
Volume
129
Issue
1
Publish Date
2011
Start Page
165
End Page
173
DOI
10.1007/s10549-011-1430-5

Language barriers and patient-centered breast cancer care.

OBJECTIVE: Provision of high quality patient-centered care is fundamental to eliminating healthcare disparities in breast cancer. We investigated physicians' experiences communicating with limited English proficient (LEP) breast cancer patients. METHODS: Survey of a random sample of California oncologists and surgeons. RESULTS: Of 301 respondents who reported treating LEP patients, 46% were oncologists, 75% male, 68% in private practice, and on average 33% of their patients had breast cancer. Only 40% reported at least sometimes using professional interpretation services. Although 75% felt they were usually able to communicate effectively with LEP patients, more than half reported difficulty discussing treatment options and prognosis, and 56% acknowledged having less-patient-centered treatment discussions with LEP breast cancer patients. In multivariate analysis, use of professional interpreters was associated with 53% lower odds of reporting less-patient-centered treatment discussions (OR 0.47; 95% CI 0.26-0.85). CONCLUSION: California surgeons and oncologists caring for breast cancer patients report substantial communication challenges when faced with a language barrier. Although use of professional interpreters is associated with more patient-centered communication, there is a low rate of professional interpreter utilization. PRACTICE IMPLICATIONS: Future research and policy should focus on increasing access to and reimbursement for professional interpreter services.

Authors
Karliner, LS; Hwang, ES; Nickleach, D; Kaplan, CP
MLA Citation
Karliner, Leah S., et al. “Language barriers and patient-centered breast cancer care..” Patient Educ Couns, vol. 84, no. 2, Aug. 2011, pp. 223–28. Pubmed, doi:10.1016/j.pec.2010.07.009.
PMID
20685068
Source
pubmed
Published In
Patient Educ Couns
Volume
84
Issue
2
Publish Date
2011
Start Page
223
End Page
228
DOI
10.1016/j.pec.2010.07.009

Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy.

UNLABELLED: Immune-regulated pathways influence multiple aspects of cancer development. In this article we demonstrate that both macrophage abundance and T-cell abundance in breast cancer represent prognostic indicators for recurrence-free and overall survival. We provide evidence that response to chemotherapy is in part regulated by these leukocytes; cytotoxic therapies induce mammary epithelial cells to produce monocyte/macrophage recruitment factors, including colony stimulating factor 1 (CSF1) and interleukin-34, which together enhance CSF1 receptor (CSF1R)-dependent macrophage infiltration. Blockade of macrophage recruitment with CSF1R-signaling antagonists, in combination with paclitaxel, improved survival of mammary tumor-bearing mice by slowing primary tumor development and reducing pulmonary metastasis. These improved aspects of mammary carcinogenesis were accompanied by decreased vessel density and appearance of antitumor immune programs fostering tumor suppression in a CD8+ T-cell-dependent manner. These data provide a rationale for targeting macrophage recruitment/response pathways, notably CSF1R, in combination with cytotoxic therapy, and identification of a breast cancer population likely to benefit from this novel therapeutic approach. SIGNIFICANCE: These findings reveal that response to chemotherapy is in part regulated by the tumor immune microenvironment and that common cytotoxic drugs induce neoplastic cells to produce monocyte/macrophage recruitment factors, which in turn enhance macrophage infiltration into mammary adenocarcinomas. Blockade of pathways mediating macrophage recruitment, in combination with chemotherapy, significantly decreases primary tumor progression, reduces metastasis, and improves survival by CD8+ T-cell-dependent mechanisms, thus indicating that the immune microenvironment of tumors can be reprogrammed to instead foster antitumor immunity and improve response to cytotoxic therapy.

Authors
DeNardo, DG; Brennan, DJ; Rexhepaj, E; Ruffell, B; Shiao, SL; Madden, SF; Gallagher, WM; Wadhwani, N; Keil, SD; Junaid, SA; Rugo, HS; Hwang, ES; Jirström, K; West, BL; Coussens, LM
MLA Citation
DeNardo, David G., et al. “Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy..” Cancer Discov, vol. 1, no. 1, June 2011, pp. 54–67. Pubmed, doi:10.1158/2159-8274.CD-10-0028.
PMID
22039576
Source
pubmed
Published In
Cancer Discov
Volume
1
Issue
1
Publish Date
2011
Start Page
54
End Page
67
DOI
10.1158/2159-8274.CD-10-0028

Is radiation indicated in patients with ductal carcinoma in situ and close or positive mastectomy margins?

PURPOSE: Resection margin status is one of the most significant factors for local recurrence in patients with ductal carcinoma in situ (DCIS) treated with breast-conserving surgery with or without radiation. However, its impact on chest wall recurrence in patients treated with mastectomy is unknown. The purpose of this study was to determine chest wall recurrence rates in women with DCIS and close (<5 mm) or positive mastectomy margins in order to evaluate the potential role of radiation therapy. METHODS AND MATERIALS: Between 1985 and 2005, 193 women underwent mastectomy for DCIS. Fifty-five patients had a close final margin, and 4 patients had a positive final margin. Axillary surgery was performed in 17 patients. Median follow-up was 8 years. Formal pathology review was conducted to measure and verify margin status. Nuclear grade, architectural pattern, and presence or absence of necrosis was recorded. RESULTS: Median pathologic size of the DCIS in the mastectomy specimen was 4.5 cm. Twenty-two patients had DCIS of >5 cm or diffuse disease. Median width of the close final margin was 2 mm. Nineteen patients had margins of <1 mm. One of these 59 patients experienced a chest wall recurrence with regional adenopathy, followed by distant metastases 2 years following skin-sparing mastectomy. The DCIS was high-grade, 4 cm, with a 5-mm deep margin. A second patient developed an invasive cancer in the chest wall 20 years after her mastectomy for DCIS. This cancer was considered a new primary site arising in residual breast tissue. CONCLUSIONS: The risk of chest wall recurrence in this series of patients is 1.7% for all patients and 3.3% for high-grade DCIS. One out of 20 (5%) patients undergoing skin sparing or total skin-sparing mastectomy experienced a chest wall recurrence. This risk of a chest wall recurrence appears sufficiently low not to warrant a recommendation for postmastectomy radiation therapy for patients with margins of <5 mm. There were too few patients with positive margins to draw any firm conclusions.

Authors
Chan, LW; Rabban, J; Hwang, ES; Bevan, A; Alvarado, M; Ewing, C; Esserman, L; Fowble, B
MLA Citation
Chan, Linda W., et al. “Is radiation indicated in patients with ductal carcinoma in situ and close or positive mastectomy margins?.” Int J Radiat Oncol Biol Phys, vol. 80, no. 1, May 2011, pp. 25–30. Pubmed, doi:10.1016/j.ijrobp.2010.01.044.
PMID
20646871
Source
pubmed
Published In
Int J Radiat Oncol Biol Phys
Volume
80
Issue
1
Publish Date
2011
Start Page
25
End Page
30
DOI
10.1016/j.ijrobp.2010.01.044

The impact of lobular histology on breast cancer treatment.

Lobular neoplasias are a distinct clinical entity with subtle differences in locoregional treatment considerations when compared with ductal cancers. Although overall surgical recommendations do not differ significantly between breast cancers of lobular versus ductal histology, there are important distinctions that should be considered as part of patient care, particularly with respect to recommendations regarding management of the contralateral breast and genetic testing. Because the lobular subtype of breast cancer is underrepresented in studies of molecular prognostic markers, the results of such testing must be interpreted with caution until they are validated specifically in patients with lobular histology. Until then, the mainstay of sound treatment decision-making remains a thorough clinical understanding of the disease and of the factors that can have an impact on outcome.

Authors
Hwang, ES
MLA Citation
Hwang, E. Shelley. “The impact of lobular histology on breast cancer treatment..” Oncology (Williston Park), vol. 25, no. 4, Apr. 2011, pp. 362–65.
PMID
21618959
Source
pubmed
Published In
Oncology (Williston Park, N.Y.)
Volume
25
Issue
4
Publish Date
2011
Start Page
362
End Page
365

The impact of preoperative magnetic resonance imaging on surgical treatment and outcomes for ductal carcinoma in situ

Background: Although magnetic resonance imaging (MRI) is a useful imaging modality for invasive cancer, its role in preoperative surgical planning for ductal carcinoma in situ (DCIS) has not been established. We sought to determine whether preoperative MRI affects surgical treatment and outcomes in women with pure DCIS. Patients and Methods: We reviewed consecutive records of women diagnosed with pure DCIS on core biopsy between 2000 and 2007. Patient characteristics, surgical planning, and outcomes were compared between patients with and without preoperative MRI. Multivariable regression was performed to determine which covariates were independently associated with mastectomy or sentinel lymph node biopsy (SLNB). Results: Of 149 women diagnosed with DCIS, 38 underwent preoperative MRI. On univariate analysis, patients undergoing MRI were younger (50 years vs. 59 years; P < .001) and had larger DCIS size on final pathology (1.6 cm vs. 1.0 cm; P = .007) than those without MRI. Mastectomy and SLNB rates were significantly higher in the preoperative MRI group (45% vs. 14%, P < .001; and 47% vs. 23%, P = .004, respectively). However, there were no differences in number of re-excisions, margin status, and margin size between the two groups. On multivariate analysis, preoperative MRI and age were independently associated with mastectomy (OR, 3.16, P = .018; OR, 0.95, P = .031, respectively), while multifocality, size, and family history were not significant predictors. Conclusion: We found a strong association between preoperative MRI and mastectomy in women undergoing treatment for DCIS. Additional studies are needed to examine the increased rates of mastectomy as a possible consequence of preoperative MRI for DCIS.© 2011 Elsevier Inc. All rights reserved.

Authors
Itakura, K; Lessing, J; Sakata, T; Heinzerling, A; Vriens, E; Wisner, D; Alvarado, M; Esserman, L; Ewing, C; Hylton, N; Hwang, ES
MLA Citation
Itakura, K., et al. “The impact of preoperative magnetic resonance imaging on surgical treatment and outcomes for ductal carcinoma in situ.” Clinical Breast Cancer, vol. 11, no. 1, Mar. 2011, pp. 33–38. Scopus, doi:10.3816/CBC.2011.n.006.
Source
scopus
Published In
Clinical Breast Cancer
Volume
11
Issue
1
Publish Date
2011
Start Page
33
End Page
38
DOI
10.3816/CBC.2011.n.006

Selection of treatment among Latina and non-Latina white women with ductal carcinoma in situ.

BACKGROUND: The growing rates of ductal carcinoma in situ (DCIS) and evidence that Latinas may underuse breast-conserving surgery (BCS) compared with white women highlight the need to better understand how treatment decisions are made in this understudied group. To help address this gap, this study compared surgery and radiation treatment decision making among white and Spanish-speaking and English-speaking Latina women with DCIS recruited from eight population-based cancer registries from 35 California counties. METHODS: Women aged ≥18 who self-identified as Latina or non-Latina white diagnosed with DCIS between 2002 and 2005 were selected from eight California Cancer Registry (CCR) regions and surveyed about their DCIS treatment decision making by telephone approximately 24 months after diagnosis. Survey data were merged with CCR hospital-based records to obtain tumor and treatment data. RESULTS: Mean age was 57 years. Multivariate analysis indicated no differences by ethnicity or language in the receipt of mastectomy vs. BCS after controlling demographic, health, and personal preferences. English-speaking Latinas were more likely to receive radiation than their Spanish-speaking or white counterparts, controlling for demographic and other factors. Among women receiving BCS, physician recommendation was the strongest predictor of receipt of radiation. CONCLUSIONS: Ethnic disparities in surgical treatment choices after breast cancer diagnosis were not seen in this cohort of women diagnosed with DCIS. Physicians play an essential role in patients' treatment choices for DCIS, particularly for adjuvant radiation.

Authors
Kaplan, CP; Nápoles, AM; Hwang, ES; Bloom, J; Stewart, S; Nickleach, D; Karliner, L
MLA Citation
Kaplan, Celia P., et al. “Selection of treatment among Latina and non-Latina white women with ductal carcinoma in situ..” J Womens Health (Larchmt), vol. 20, no. 2, Feb. 2011, pp. 215–23. Pubmed, doi:10.1089/jwh.2010.1986.
PMID
21128819
Source
pubmed
Published In
J Womens Health (Larchmt)
Volume
20
Issue
2
Publish Date
2011
Start Page
215
End Page
223
DOI
10.1089/jwh.2010.1986

Intraoperative frozen section analysis of sentinel lymph nodes in breast cancer patients: a meta-analysis and single-institution experience.

BACKGROUND: Accurate intraoperative pathologic examination of sentinel lymph nodes (SLNs) has been an important tool that can reduce the need for reoperations in patients with SLN-positive breast cancer. The objective of the current study was to determine the accuracy of intraoperative frozen section (IFS) of SLNs during breast cancer surgery. METHODS: The authors retrospectively reviewed the records of 326 patients with breast cancer who underwent IF analysis of SLNs at a single institution. Then, they conducted a meta-analysis that included 47 published studies of IFS of SLNs in patients with breast cancer. RESULTS: Hematoxylin and eosin (H&E) staining revealed metastasis in SLNs in 99 patients (30.4%), including 61 patients with macrometastasis (MAM) (>2 mm) (the MAM group) and 38 patients with micrometastasis (Mi) or isolated tumor cell (ITC) deposits (the Mi/ITC group). The overall sensitivity of the institutional series was 60.6% (60 of 99 patients), and overall specificity was 100% (227 of 227 true negatives). The sensitivity of IFS was significantly lower in the Mi/ITC group (28.9%) than in the MAM group (80.3%; P < .0001). According to the meta-analysis of published studies and data from the author's institution (47 studies, for a total of 13,062 patients who underwent SLN dissection with IFS of SLNs), the mean sensitivity was 73%, and the mean specificity was 100%. The mean sensitivity was 94% for the MAM group and 40% for the Mi/ITC group. CONCLUSIONS: IFS of SLNs was more reliable for detecting MAM than for detecting Mi/ITC deposits. It lacked sufficient accuracy to rule out Mi/ITC deposits.

Authors
Liu, L-C; Lang, JE; Lu, Y; Roe, D; Hwang, SE; Ewing, CA; Esserman, LJ; Morita, E; Treseler, P; Leong, SP
MLA Citation
Liu, Liang-Chih, et al. “Intraoperative frozen section analysis of sentinel lymph nodes in breast cancer patients: a meta-analysis and single-institution experience..” Cancer, vol. 117, no. 2, Jan. 2011, pp. 250–58. Pubmed, doi:10.1002/cncr.25606.
PMID
20818649
Source
pubmed
Published In
Cancer
Volume
117
Issue
2
Publish Date
2011
Start Page
250
End Page
258
DOI
10.1002/cncr.25606

Spontaneous resolution of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis.

Secondary hemophagocytic lymphohistiocytosis (sHLH) is a reactive, proliferative disorder of the immune system resulting in lymphohistiocytic proliferation, hemophagocytosis, and cytokine dysregulation. The most common infectious trigger in sHLH is Epstein-Barr virus (EBV-HLH). Current treatment protocols for EBV-HLH have a cure rate of approximately 75%; however, there are significant toxicities associated with these therapies. We present two patients with EBV-HLH who experienced spontaneous resolution of their disease prior to the initiation of therapy, suggesting there may be a subgroup of patients with EBV-HLH who do well with conservative management and can avoid potentially toxic therapies.

Authors
Belyea, B; Hinson, A; Moran, C; Hwang, E; Heath, J; Barfield, R
MLA Citation
Belyea, Brian, et al. “Spontaneous resolution of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis..” Pediatr Blood Cancer, vol. 55, no. 4, Oct. 2010, pp. 754–56. Pubmed, doi:10.1002/pbc.22618.
PMID
20806367
Source
pubmed
Published In
Pediatr Blood Cancer
Volume
55
Issue
4
Publish Date
2010
Start Page
754
End Page
756
DOI
10.1002/pbc.22618

Impact of chemotherapy on postoperative complications after mastectomy and immediate breast reconstruction.

OBJECTIVES: To determine the impact of chemotherapy and the timing of chemotherapy on postoperative outcomes after mastectomy and immediate breast reconstruction. DESIGN: Retrospective review. SETTING: University tertiary care institution. PATIENTS: One hundred sixty-three consecutive patients undergoing mastectomy and immediate breast reconstruction. INTERVENTION: Systemic chemotherapy for breast cancer. MAIN OUTCOME MEASURES: Postoperative complications following mastectomy and immediate breast reconstruction. RESULTS: One hundred sixty-three patients underwent mastectomy and immediate breast reconstruction during the study period, with a mean postoperative follow-up of 19.2 months. Sixty-six percent of the patients had expander/implant reconstruction, while 33% underwent autologous reconstruction. Fifty-seven patients received neoadjuvant chemotherapy and 41 received postoperative chemotherapy. Eighteen patients (44%) in the adjuvant chemotherapy cohort developed postoperative infections, compared with 13 patients (23%) in the neoadjuvant chemotherapy group and 16 patients (25%) who did not receive any chemotherapy (P = .05). Overall, 31% of patients had a complication requiring an unplanned return to the operating room; this rate did not differ between groups (P = .79). Of patients who underwent expander/implant reconstruction, 8 women (26%) in the neoadjuvant chemotherapy cohort, 7 women (22%) in the adjuvant chemotherapy cohort, and 8 women (18%) without chemotherapy required expander or implant removal (P = .70). CONCLUSIONS: Although the highest rate of surgical site infections was in the adjuvant chemotherapy group, there were no differences between groups with respect to unplanned return to the operating room, expander loss, and donor-site complications. Neither the inclusion of chemotherapy nor the timing of its administration significantly affected the complication rates after mastectomy and immediate breast reconstruction in this population.

Authors
Warren Peled, A; Itakura, K; Foster, RD; Hamolsky, D; Tanaka, J; Ewing, C; Alvarado, M; Esserman, LJ; Hwang, ES
MLA Citation
Warren Peled, Anne, et al. “Impact of chemotherapy on postoperative complications after mastectomy and immediate breast reconstruction..” Arch Surg, vol. 145, no. 9, Sept. 2010, pp. 880–85. Pubmed, doi:10.1001/archsurg.2010.163.
PMID
20855759
Source
pubmed
Published In
Arch Surg
Volume
145
Issue
9
Publish Date
2010
Start Page
880
End Page
885
DOI
10.1001/archsurg.2010.163

Status of intraductal therapy for ductal carcinoma in Situ

The intraductal approach is particularly appealing in the setting of ductal carcinoma in situ (DCIS), a preinvasive breast neoplasm that is thought to be entirely intraductal in its extent. Based on an emerging understanding of the anatomy of the ductal system as well as novel techniques to leverage the access accorded by the intraductal approach, researchers are actively exploring how ductal lavage, ductoscopy, and intraductal infusion of therapeutic agents may enhance breast cancer treatment. Both cytologic and molecular diagnostics continue to improve, and work is ongoing to identify the most effective diagnostic biomarkers for DCIS and cancer, although optimal targeting of the diseased duct remains an important consideration. Ductoscopy holds potential in detection of occult intraductal lesions, and ductoscopically guided lumpectomy could increase the likelihood of a more comprehensive surgical excision. Exciting pilot studies are in progress to determine the safety and feasibility of intraductal chemotherapy infusion. These studies are an important starting point for future investigations of intraductal ablative therapy for DCIS, because as our knowledge and techniques evolve, it is likely that DCIS may be the target most amenable to treatment by intraductal therapy. If such studies are successful, these approaches will allow an important and meaningful transformation in treatment options for women diagnosed with DCIS. © The Author(s) 2010.

Authors
Flanagan, M; Love, S; Hwang, ES
MLA Citation
Flanagan, M., et al. “Status of intraductal therapy for ductal carcinoma in Situ.” Current Breast Cancer Reports, vol. 2, no. 2, June 2010, pp. 75–82. Scopus, doi:10.1007/s12609-010-0015-3.
Source
scopus
Published In
Current Breast Cancer Reports
Volume
2
Issue
2
Publish Date
2010
Start Page
75
End Page
82
DOI
10.1007/s12609-010-0015-3

Fluvastatin reduces proliferation and increases apoptosis in women with high grade breast cancer.

The purpose of this study is to determine the biologic impact of short-term lipophilic statin exposure on in situ and invasive breast cancer through paired tissue, blood and imaging-based biomarkers. A perioperative window trial of fluvastatin was conducted in women with a diagnosis of DCIS or stage 1 breast cancer. Patients were randomized to high dose (80 mg/day) or low dose (20 mg/day) fluvastatin for 3-6 weeks before surgery. Tissue (diagnostic core biopsy/final surgical specimen), blood, and magnetic resonance images were obtained before/after treatment. The primary endpoint was Ki-67 (proliferation) reduction. Secondary endpoints were change in cleaved caspase-3 (CC3, apoptosis), MRI tumor volume, and serum C-reactive protein (CRP, inflammation). Planned subgroup analyses compared disease grade, statin dose, and estrogen receptor status. Forty of 45 patients who enrolled completed the protocol; 29 had paired Ki-67 primary endpoint data. Proliferation of high grade tumors decreased by a median of 7.2% (P = 0.008), which was statistically greater than the 0.3% decrease for low grade tumors. Paired data for CC3 showed tumor apoptosis increased in 38%, remained stable in 41%, and decreased in 21% of subjects. More high grade tumors had an increase in apoptosis (60 vs. 13%; P = 0.015). Serum CRP did not change, but cholesterol levels were significantly lower post statin exposure (P < 0.001). Fluvastatin showed measurable biologic changes by reducing tumor proliferation and increasing apoptotic activity in high-grade, stage 0/1 breast cancer. Effects were only evident in high grade tumors. These results support further evaluation of statins as chemoprevention for ER-negative high grade breast cancers.

Authors
Garwood, ER; Kumar, AS; Baehner, FL; Moore, DH; Au, A; Hylton, N; Flowers, CI; Garber, J; Lesnikoski, B-A; Hwang, ES; Olopade, O; Port, ER; Campbell, M; Esserman, LJ
MLA Citation
Garwood, Elisabeth R., et al. “Fluvastatin reduces proliferation and increases apoptosis in women with high grade breast cancer..” Breast Cancer Res Treat, vol. 119, no. 1, Jan. 2010, pp. 137–44. Pubmed, doi:10.1007/s10549-009-0507-x.
PMID
19728082
Source
pubmed
Published In
Breast Cancer Res Treat
Volume
119
Issue
1
Publish Date
2010
Start Page
137
End Page
144
DOI
10.1007/s10549-009-0507-x

The impact of surgery on ductal carcinoma in situ outcomes: the use of mastectomy.

Mastectomy has been the historical mainstay of treatment for ductal carcinoma in situ (DCIS), but over time, there have been significant changes in its use for preinvasive breast cancer. Although there was an early reduction in mastectomy rates for DCIS with the introduction of breast-conserving surgery, in some groups, the rates of both mastectomy and contralateral mastectomy for DCIS have increased in recent years. Due to advances in breast cancer screening as well as improvements in breast reconstruction, mastectomy will continue to be an important and acceptable treatment option. Recurrence is rare following mastectomy for DCIS. Nevertheless, there remains a need to follow patients for in-breast, nodal, or contralateral breast events, which can occur long after the index DCIS has been treated. Since up to 70% of women with newly diagnosed DCIS have disease that can be managed with breast-conserving surgery, patient counseling is imperative to ensure the best use of this option for DCIS, given that mastectomy does not significantly impact survival in this setting.

Authors
Hwang, ES
MLA Citation
Hwang, E. Shelley. “The impact of surgery on ductal carcinoma in situ outcomes: the use of mastectomy..” J Natl Cancer Inst Monogr, vol. 2010, no. 41, 2010, pp. 197–99. Pubmed, doi:10.1093/jncimonographs/lgq032.
PMID
20956829
Source
pubmed
Published In
J Natl Cancer Inst Monogr
Volume
2010
Issue
41
Publish Date
2010
Start Page
197
End Page
199
DOI
10.1093/jncimonographs/lgq032

Genetic and phenotypic characteristics of pleomorphic lobular carcinoma in situ of the breast.

The clinical, pathologic, and molecular features of pleomorphic lobular carcinoma in situ (PLCIS) and the relationship of PLCIS to classic LCIS (CLCIS) are poorly defined. In this study, we analyzed 31 cases of PLCIS (13 apocrine and 18 nonapocrine subtypes) and compared the clinical, pathologic, immunophenotypic, and genetic characteristics of these cases with those of 24 cases of CLCIS. Biomarker expression was examined using immunostaining for E-cadherin, gross cystic disease fluid protein-15, estrogen, progesterone, androgen receptor, human epidermal growth factor receptor2, CK5/6, and Ki67. Array-based comparative genomic hybridization to assess the genomic alterations was performed using microdissected formalin-fixed paraffin-embedded samples. Patients with PLCIS presented with mammographic abnormalities. Histologically, the tumor cells were dyshesive and showed pleomorphic nuclei, and there was often associated necrosis and microcalcifications. All lesions were E-cadherin negative. Compared with CLCIS, PLCIS showed significantly higher Ki67 index, lower estrogen receptor and progesterone receptor expression, and higher incidence of HER2 gene amplification. The majority of PLCIS and CLCIS demonstrated loss of 16q and gain of 1q. Apocrine PLCIS had significantly more genomic alterations than CLCIS and nonapocrine PLCIS. Although lack of E-cadherin expression and the 16q loss and 1q gain-array-based comparative genomic hybridization pattern support a relationship to CLCIS, PLCIS has clinical, mammographic, histologic, immunophenotypic, and genetic features that distinguish it from CLCIS. The histologic features, biomarker profile, and genomic instability observed in PLCIS suggest a more aggressive phenotype than CLCIS. However, clinical follow-up studies will be required to define the natural history and most appropriate management of these lesions.

Authors
Chen, Y-Y; Hwang, E-SS; Roy, R; DeVries, S; Anderson, J; Wa, C; Fitzgibbons, PL; Jacobs, TW; MacGrogan, G; Peterse, H; Vincent-Salomon, A; Tokuyasu, T; Schnitt, SJ; Waldman, FM
MLA Citation
Chen, Yunn-Yi, et al. “Genetic and phenotypic characteristics of pleomorphic lobular carcinoma in situ of the breast..” Am J Surg Pathol, vol. 33, no. 11, Nov. 2009, pp. 1683–94. Pubmed, doi:10.1097/PAS.0b013e3181b18a89.
PMID
19701073
Source
pubmed
Published In
American Journal of Surgical Pathology
Volume
33
Issue
11
Publish Date
2009
Start Page
1683
End Page
1694
DOI
10.1097/PAS.0b013e3181b18a89

Bacteriologic features of surgical site infections following breast surgery.

BACKGROUND: Perioperative antibiotic prophylaxis to prevent surgical site infections (SSIs) after breast surgery is common practice. Breast SSIs were investigated to determine bacterial isolates, resistance patterns, and the appropriateness of cefazolin, the authors' institution's current regimen for perioperative antibiotic prophylaxis. METHODS: A retrospective review of 53 patients with culture-positive breast SSIs between June 1997 and August 2008 identified patient characteristics, bacterial isolates, and microbial resistance patterns. RESULTS: Among the 53 patients with positive cultures, 42% (n = 22) had undergone mastectomy, and 34% (n = 18) had undergone lumpectomy. Sixty-three bacterial isolates were identified, with 15% of SSIs being polymicrobial. Of the isolates, 49% (n = 31) were gram-negative bacteria. There was only 1 case of methicillin-resistant Staphylococcus aureus. Eight of 63 (13%) gram-negative isolates were cefazolin resistant. CONCLUSIONS: Gram-negative SSIs constituted half of the SSIs in this breast surgery cohort. Of all breast isolates, 17.5% were resistant to cefazolin. On the basis of these findings, antibiotic prophylaxis regimens alternative to cefazolin should be considered.

Authors
Mukhtar, RA; Throckmorton, AD; Alvarado, MD; Ewing, CA; Esserman, LJ; Chiu, C; Hwang, ES
MLA Citation
Mukhtar, Rita A., et al. “Bacteriologic features of surgical site infections following breast surgery..” Am J Surg, vol. 198, no. 4, Oct. 2009, pp. 529–31. Pubmed, doi:10.1016/j.amjsurg.2009.06.006.
PMID
19800462
Source
pubmed
Published In
Am J Surg
Volume
198
Issue
4
Publish Date
2009
Start Page
529
End Page
531
DOI
10.1016/j.amjsurg.2009.06.006

Pathologic and biologic response to preoperative endocrine therapy in patients with ER-positive ductal carcinoma in situ.

BACKGROUND: Endocrine therapy is commonly recommended in the adjuvant setting for patients as treatment for ductal carcinoma in situ (DCIS). However, it is unknown whether a neoadjuvant (preoperative) anti-estrogen approach to DCIS results in any biological change. This study was undertaken to investigate the pathologic and biomarker changes in DCIS following neoadjuvant endocrine therapy compared to a group of patients who did not undergo preoperative anti-estrogenic treatment to determine whether such treatment results in detectable histologic alterations. METHODS: Patients (n = 23) diagnosed with ER-positive pure DCIS by stereotactic core biopsy were enrolled in a trial of neoadjuvant anti-estrogen therapy followed by definitive excision. Patients on hormone replacement therapy, with palpable masses, or with histologic or clinical suspicion of invasion were excluded. Premenopausal women were treated with tamoxifen and postmenopausal women were treated with letrozole. Pathologic markers of proliferation, inflammation, and apoptosis were evaluated at baseline and at three months.Biomarker changes were compared to a cohort of patients who had not received preoperative treatment. RESULTS: Median age of the cohort was 53 years (range 38-78); 14 were premenopausal. Following treatment, predominant morphologic changes included increased multinucleated histiocytes and degenerated cells, decreased duct extension, and prominent periductal fibrosis. Two postmenopausal patients had ADH only with no residual DCIS at excision. Postmenopausal women on letrozole had significant reduction of PR, and Ki67 as well as increase in CD68-positive cells. For premenopausal women on tamoxifen treatment, the only significant change was increase in CD68. No change in cleaved caspase 3 was found. Two patients had invasive cancer at surgery. CONCLUSION: Preoperative therapy for DCIS is associated with significant pathologic alterations. These changes may be clinically significant. Further work is needed to identify which women may be the best candidates for such treatment for DCIS, and whether best responders may safely avoid surgical intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT00290745.

Authors
Chen, Y-Y; DeVries, S; Anderson, J; Lessing, J; Swain, R; Chin, K; Shim, V; Esserman, LJ; Waldman, FM; Hwang, ES
MLA Citation
Chen, Yunn-Yi, et al. “Pathologic and biologic response to preoperative endocrine therapy in patients with ER-positive ductal carcinoma in situ..” Bmc Cancer, vol. 9, Aug. 2009. Pubmed, doi:10.1186/1471-2407-9-285.
PMID
19689789
Source
pubmed
Published In
Bmc Cancer
Volume
9
Publish Date
2009
Start Page
285
DOI
10.1186/1471-2407-9-285

Protein acetylation and histone deacetylase expression associated with malignant breast cancer progression.

PURPOSE: Excess histone deacetylase (HDAC) activity can induce hypoacetylation of histone and nonhistone protein substrates, altering gene expression patterns and cell behavior potentially associated with malignant transformation. However, HDAC expression and protein acetylation have not been studied in the context of breast cancer progression. EXPERIMENTAL DESIGN: We assessed expression levels of acetylated histone H4 (ac-H4), ac-H4K12, ac-tubulin, HDAC1, HDAC2, and HDAC6 in 22 reduction mammoplasties and in 58 specimens with synchronous normal epithelium, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) components. Differences among groups were tested for significance using nonparametric tests. RESULTS: From normal epithelium to DCIS, there was a marked reduction in histone acetylation (P < 0.0001). Most cases showed similar levels of acetylation in DCIS and IDC, although some showed further reduction of ac-H4 and ac-H4K12 from DCIS to IDC. Expression of HDAC1, HDAC2, and HDAC6 was also significantly reduced but by a smaller magnitude. Greater reductions of H4 acetylation and HDAC1 levels were observed from normal to DCIS in estrogen receptor-negative compared with estrogen receptor-positive, and in high-grade compared with non-high-grade tumors. CONCLUSION: Overall, there was a global pattern of hypoacetylation associated with progression from normal to DCIS to IDC. These findings suggest that the reversal of this hypoacetylation in DCIS and IDC could be an early measure of HDAC inhibitor activity.

Authors
Suzuki, J; Chen, Y-Y; Scott, GK; Devries, S; Chin, K; Benz, CC; Waldman, FM; Hwang, ES
MLA Citation
Suzuki, Junko, et al. “Protein acetylation and histone deacetylase expression associated with malignant breast cancer progression..” Clin Cancer Res, vol. 15, no. 9, May 2009, pp. 3163–71. Pubmed, doi:10.1158/1078-0432.CCR-08-2319.
PMID
19383825
Source
pubmed
Published In
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Volume
15
Issue
9
Publish Date
2009
Start Page
3163
End Page
3171
DOI
10.1158/1078-0432.CCR-08-2319

Prognostic implications of positive nonsentinel lymph nodes removed during selective sentinel lymphadenectomy for breast cancer.

Nonsentinel lymph nodes (SLNs) are commonly removed at the time of selective sentinel lymphadenectomy (SSL). Their predictive value for the rest of the nodal basin is unknown. A retrospective review of 436 breast cancer patients who underwent SSL between 12/97 and 04/03 at a single institution. One-hundred nineteen patients had non-SLNs removed at SSL; eight were positive (6.7%). Positive non-SLNs predicted that SLNs would also be positive (p = 0.008). There was no difference in rates of additional positive nodes found on completion axillary node dissection between the non-SLN and SLN positive patients (p = 0.62). After adjustment for covariates, the presence of positive non-SLNs was not associated with poorer disease free survival (p = 0.24), time to systemic recurrence (p = 0.57), or overall survival (p = 0.70). Positive non-SLNs removed during SSL are not a significant risk factor for additional positive nodes on completion axillary nodal dissection (CALND) or for worse survival than positive SLNs.

Authors
Lang, JE; Liu, L-C; Lu, Y; Jenkins, T; Hwang, SE; Esserman, LJ; Ewing, CA; Alvarado, M; Morita, E; Treseler, P; Leong, SP
MLA Citation
Lang, Julie E., et al. “Prognostic implications of positive nonsentinel lymph nodes removed during selective sentinel lymphadenectomy for breast cancer..” Breast J, vol. 15, no. 3, May 2009, pp. 242–46. Pubmed, doi:10.1111/j.1524-4741.2009.00712.x.
PMID
19645778
Source
pubmed
Published In
Breast J
Volume
15
Issue
3
Publish Date
2009
Start Page
242
End Page
246
DOI
10.1111/j.1524-4741.2009.00712.x

Total skin-sparing mastectomy: complications and local recurrence rates in 2 cohorts of patients.

PURPOSE: Dissemination of the total skin-sparing mastectomy (TSSM) technique is limited by concerns of nipple viability, flap necrosis, local recurrence risk, and the technical challenge of this procedure. We sought to define the impact of surgical and reconstructive variables on complication rates and assess how changes in technique affect outcomes. PATIENTS AND METHODS: We compared the outcomes of TSSM in 2 cohorts of patients. Cohort 1: the first 64 TSSM procedures performed at our institution, between 2001 and 2005. Cohort 2: 106 TSSM performed between 2005 and 2007. Outcomes of cohort 1 were analyzed in 2005. At that time, potential risk factors for complications were identified, and efforts to minimize these risks by altering operative and reconstructive technique were then applied to patients in cohort 2. The impact of these changes on outcomes was assessed. Logistic regression was used to determine the association between predictor variables and adverse outcomes (Stata 10). RESULTS: The predominant incision type in cohort 2 involved less than a third of the nipple areola complex (NAC), and the most frequent reconstruction technique was tissue expander placement. Between cohort 1 and cohort 2, nipple survival rates rose from 80% to 95% (P = 0.003) and complication rates declined: necrotic complications (30% --> 13%; P = 0.01), implant loss (31% --> 10%; P = 0.005), skin flap necrosis (16%-11%; not significant), and significant infections (17%-9%, not significant). Incisions involving >30% of the NAC (P < 0.001) and reconstruction with autologous tissue (P < 0.001) were independent risk factors for necrotic complications. The local recurrence rate was 0.6% at a median follow-up of 13 months (range, 1-65), with no recurrences in the NAC. CONCLUSION: Focused improvement in technique has resulted in the development of TSSM as a successful intervention at our institution that is oncologically safe with high nipple viability and early low rates of recurrence. Identifying factors that contribute to complications and changing surgical and reconstructive techniques to eliminate risk factors has greatly improved outcomes.

Authors
Garwood, ER; Moore, D; Ewing, C; Hwang, ES; Alvarado, M; Foster, RD; Esserman, LJ
MLA Citation
Garwood, Elisabeth R., et al. “Total skin-sparing mastectomy: complications and local recurrence rates in 2 cohorts of patients..” Ann Surg, vol. 249, no. 1, Jan. 2009, pp. 26–32. Pubmed, doi:10.1097/SLA.0b013e31818e41a7.
PMID
19106672
Source
pubmed
Published In
Ann Surg
Volume
249
Issue
1
Publish Date
2009
Start Page
26
End Page
32
DOI
10.1097/SLA.0b013e31818e41a7

Is it necessary to harvest additional lymph nodes after resection of the most radioactive sentinel lymph node in breast cancer?

BACKGROUND: No consensus exists about the number of sentinel lymph nodes (SLNs) that should be removed based on radioactivity counts in breast cancer, although the "10% rule" is often used. We hypothesized that the node with the highest radioactivity would have the strongest probability of being a positive SLN, and we sought to determine the lowest radioactive count of a node harboring cancer. STUDY DESIGN: We retrospectively studied 332 breast cancer patients who underwent lymphoscintigraphy by injection of technetium 99m-labeled thiosulfate colloid and sentinel lymphadenectomy (SL) between 1997 and 2006, with intraoperative determination of radioactive counts of nodes by a gamma probe. All SLNs were examined by permanent sections consisting of at least 3 levels of 40- to 100-mum intervals for hematoxylin and eosin evaluation, with or without immunohistochemical staining for cytokeratins. RESULTS: Seventy-four percent of patients had more than 1 SLN removed (mean 2.8 per patient); 23.5% had SLN metastasis. Of the node-positive patients, the hottest SLN was positive in 85.9% (67 of 78). Five of the 78 patients (6.4%) with positive nodes had counts less than 10% of those of the hottest node. The lowest radioactive count of a positive SLN was 4.2% of that of the hottest node. Lymphatic mapping based on the 10% rule could greatly improve the false-negative rates compared with removing only the hottest SLN (14.1% versus 6.4%). CONCLUSIONS: Most positive SLNs had the highest radioactivity. Our institutional experience indicates that to obtain an acceptable false-negative rate, nodes should be removed until the 10% rule is met.

Authors
Liu, L-C; Lang, JE; Jenkins, T; Lu, Y; Ewing, CA; Hwang, SE; Sokol, S; Alvarado, M; Esserman, LJ; Morita, E; Treseler, P; Leong, SP
MLA Citation
Liu, Liang-Chih, et al. “Is it necessary to harvest additional lymph nodes after resection of the most radioactive sentinel lymph node in breast cancer?.” J Am Coll Surg, vol. 207, no. 6, Dec. 2008, pp. 853–58. Pubmed, doi:10.1016/j.jamcollsurg.2008.08.008.
PMID
19183531
Source
pubmed
Published In
J Am Coll Surg
Volume
207
Issue
6
Publish Date
2008
Start Page
853
End Page
858
DOI
10.1016/j.jamcollsurg.2008.08.008

Type and Duration of Exogenous Hormone Use Affects Breast Cancer Histology

Authors
Hwang, ES
MLA Citation
Hwang, E. S. Type and Duration of Exogenous Hormone Use Affects Breast Cancer Histology. Vol. 19, 2008, pp. 23–25. Scopus, doi:10.1016/S1043-321X(08)80004-5.
Source
scopus
Volume
19
Publish Date
2008
Start Page
23
End Page
25
DOI
10.1016/S1043-321X(08)80004-5

Surgery for palliation and treatment of advanced breast cancer.

Authors
Alvarado, M; Ewing, CA; Elyassnia, D; Foster, RD; Shelley Hwang, E
MLA Citation
Alvarado, Michael, et al. “Surgery for palliation and treatment of advanced breast cancer..” Surg Oncol, vol. 16, no. 4, Dec. 2007, pp. 249–57. Pubmed, doi:10.1016/j.suronc.2007.08.007.
PMID
17976977
Source
pubmed
Published In
Surgical Oncology
Volume
16
Issue
4
Publish Date
2007
Start Page
249
End Page
257
DOI
10.1016/j.suronc.2007.08.007

Association between breast density and subsequent breast cancer following treatment for ductal carcinoma in situ.

BACKGROUND: Risk of invasive cancer following treatment for ductal carcinoma in situ (DCIS) is associated with both treatment- and tumor-related factors. However, it is unknown whether stromal factors such as breast density may also influence subsequent invasive breast events. We investigated whether breast density is an independent predictor of subsequent breast events among women treated for DCIS. POPULATION: A prospective cohort study of 3,274 women ages 30 to 93 in the Breast Cancer Surveillance Consortium treated with lumpectomy for DCIS between 1993 and 2005. All subjects had an American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) breast density measure recorded prior to diagnosis. METHODS: Ipsilateral and contralateral breast cancer following lumpectomy for DCIS were ascertained through state tumor registries, regional Surveillance Epidemiology and End Results program or pathology databases. A Cox proportional hazard model was used to compare adjusted risk of breast cancer among women with high (BI-RADS 3 or 4) versus low (BI-RADS 1 or 2) breast density. RESULTS: During a median follow-up period of 39 months (0-132 months), 133 women developed invasive breast cancer. After adjusting for age and radiation treatment, high breast density was associated with increased hazard for contralateral (hazard ratio, 3.1; 95% confidence interval, 1.6-6.1) but not ipsilateral (hazard ratio, 1.0; 95% confidence interval, 0.6-1.6) invasive breast events. CONCLUSION: High breast density is associated with contralateral, but not ipsilateral, invasive breast cancer following lumpectomy for DCIS. Thus, women with DCIS and high breast density may especially benefit from antiestrogenic therapy to reduce the risk of contralateral invasive disease.

Authors
Hwang, ES; Miglioretti, DL; Ballard-Barbash, R; Weaver, DL; Kerlikowske, K; National Cancer Institute Breast Cancer Surveillance Consortium,
MLA Citation
Hwang, E. Shelley, et al. “Association between breast density and subsequent breast cancer following treatment for ductal carcinoma in situ..” Cancer Epidemiol Biomarkers Prev, vol. 16, no. 12, Dec. 2007, pp. 2587–93. Pubmed, doi:10.1158/1055-9965.EPI-07-0458.
PMID
18086762
Source
pubmed
Published In
Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology
Volume
16
Issue
12
Publish Date
2007
Start Page
2587
End Page
2593
DOI
10.1158/1055-9965.EPI-07-0458

Response [5]

Authors
Ozanne, EM; Hwang, ES; Esserman, LJ
MLA Citation
Ozanne, E. M., et al. “Response [5].” Breast Journal, vol. 13, no. 5, 1 Sept. 2007, pp. 540–42. Scopus, doi:10.1111/j.1524-4741.2007.00487.x.
Source
scopus
Published In
Breast Journal
Volume
13
Issue
5
Publish Date
2007
Start Page
540
End Page
542
DOI
10.1111/j.1524-4741.2007.00487.x

Identification of a robust gene signature that predicts breast cancer outcome in independent data sets.

BACKGROUND: Breast cancer is a heterogeneous disease, presenting with a wide range of histologic, clinical, and genetic features. Microarray technology has shown promise in predicting outcome in these patients. METHODS: We profiled 162 breast tumors using expression microarrays to stratify tumors based on gene expression. A subset of 55 tumors with extensive follow-up was used to identify gene sets that predicted outcome. The predictive gene set was further tested in previously published data sets. RESULTS: We used different statistical methods to identify three gene sets associated with disease free survival. A fourth gene set, consisting of 21 genes in common to all three sets, also had the ability to predict patient outcome. To validate the predictive utility of this derived gene set, it was tested in two published data sets from other groups. This gene set resulted in significant separation of patients on the basis of survival in these data sets, correctly predicting outcome in 62-65% of patients. By comparing outcome prediction within subgroups based on ER status, grade, and nodal status, we found that our gene set was most effective in predicting outcome in ER positive and node negative tumors. CONCLUSION: This robust gene selection with extensive validation has identified a predictive gene set that may have clinical utility for outcome prediction in breast cancer patients.

Authors
Korkola, JE; Blaveri, E; DeVries, S; Moore, DH; Hwang, ES; Chen, Y-Y; Estep, ALH; Chew, KL; Jensen, RH; Waldman, FM
MLA Citation
Korkola, James E., et al. “Identification of a robust gene signature that predicts breast cancer outcome in independent data sets..” Bmc Cancer, vol. 7, Apr. 2007. Pubmed, doi:10.1186/1471-2407-7-61.
PMID
17428335
Source
pubmed
Published In
Bmc Cancer
Volume
7
Publish Date
2007
Start Page
61
DOI
10.1186/1471-2407-7-61

1-5 Multiple primary tumours in women following breast cancer, 1973-2000

Authors
Hwang, ES
MLA Citation
Hwang, E. S. 1-5 Multiple primary tumours in women following breast cancer, 1973-2000. Vol. 18, 2007, pp. 29–30. Scopus, doi:10.1016/S1043-321X(07)80010-5.
Source
scopus
Volume
18
Publish Date
2007
Start Page
29
End Page
30
DOI
10.1016/S1043-321X(07)80010-5

Ductal carcinoma in situ in BRCA mutation carriers.

PURPOSE: The current literature suggests that ductal carcinoma in situ (DCIS) of the breast is infrequently diagnosed in patients with BRCA germline mutations. We studied women at high risk of hereditary breast cancer syndromes who underwent testing for BRCA1 and BRCA2 to estimate DCIS prevalence and incidence in known BRCA-positive women compared with high-risk women who were mutation negative. METHODS: We analyzed breast event outcomes in a retrospective cohort of 129 BRCA-positive and 269 BRCA-negative women undergoing genetic testing for a BRCA mutation between September 1996 and December 2003 at University of California, San Francisco. We estimated the frequency of DCIS and invasive cancer and time to breast events from birth using a Cox proportional hazard model for competing risks. Histologic grade of DCIS was also compared between groups. RESULTS: Among BRCA carriers, 48 (37%) had DCIS (with or without invasive cancer) compared with 92 noncarriers (34%). Univariate analysis showed that both DCIS and invasive cancer had an earlier onset in mutation carriers than in noncarriers, although on a per-woman basis, this difference was not statistically significant. High-grade DCIS was more common in BRCA1 mutation carriers than in patients without a mutation (P = .02). CONCLUSION: DCIS is equally as prevalent in patients who carry deleterious BRCA mutations as in high familial-risk women who are noncarriers, but occurs at an earlier age. Our results argue for the consideration of DCIS as a criterion for BRCA risk assessments with appropriate weighting in prediction models such as BRCAPRO.

Authors
Hwang, ES; McLennan, JL; Moore, DH; Crawford, BB; Esserman, LJ; Ziegler, JL
MLA Citation
Hwang, E. Shelley, et al. “Ductal carcinoma in situ in BRCA mutation carriers..” J Clin Oncol, vol. 25, no. 6, Feb. 2007, pp. 642–47. Pubmed, doi:10.1200/JCO.2005.04.0345.
PMID
17210933
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
25
Issue
6
Publish Date
2007
Start Page
642
End Page
647
DOI
10.1200/JCO.2005.04.0345

Type and duration of exogenous hormone use affects breast cancer histology.

BACKGROUND: It is unclear whether hormone replacement therapy (HRT), in addition to increasing risk for breast cancer, affects the type of breast cancer diagnosed. We conducted this investigation to assess whether the type of hormone used (none, estrogen, progesterone, or combined) and duration of use influences subsequent breast cancer histology. METHODS: We performed a retrospective cohort analysis among women listed as incident cases of breast malignancy in the Kaiser Permanente Northern California Cancer Registry during 2003 (n = 2830). Type and duration of hormone used (none, estrogen, progesterone, or combined) before breast cancer diagnosis was obtained from electronic pharmacy records. The association between type and duration of hormone use with characteristics of subsequent breast cancers was examined. RESULTS: Among women aged >50 years (n = 1701), any use of estrogen, progesterone, or combination therapy was not associated with an increased risk of estrogen receptor (ER)-positive disease. However, >6 months' use of combined HRT increased the odds of ER-positive tumors (odds ratio, 1.65; 95% confidence interval, 1.07-2.5; P = .02). Estrogen HRT patients were more likely than nonusers to present with low-grade (P = .05), and early-stage tumors (P = .03). This trend was not seen in combined HRT users. CONCLUSIONS: Short-duration HRT did not increase the likelihood of ER-positive breast cancer. However, prolonged duration of combined HRT, but not estrogen or progesterone alone, resulted in a marked increase in ER-positive disease. Our findings suggest that the effect of combined HRT on breast cancer incidence or progression is not immediate and that long-term use is more likely to affect breast cancer histology.

Authors
Kumar, AS; Cureton, E; Shim, V; Sakata, T; Moore, DH; Benz, CC; Esserman, LJ; Hwang, ES
MLA Citation
Kumar, Anjali S., et al. “Type and duration of exogenous hormone use affects breast cancer histology..” Ann Surg Oncol, vol. 14, no. 2, Feb. 2007, pp. 695–703. Pubmed, doi:10.1245/s10434-006-9129-2.
PMID
17103262
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
14
Issue
2
Publish Date
2007
Start Page
695
End Page
703
DOI
10.1245/s10434-006-9129-2

Information exchange and decision making in the treatment of Latina and white women with ductal carcinoma in situ.

The natural history of ductal carcinoma in situ (DCIS) is largely unknown, and its optimal treatment remains controversial. Using semi-structured interviews, this study compared 18 White and 16 Latina women's understanding of their DCIS diagnosis, treatment decision-making processes, and satisfaction with care. Ethnic differences were observed in cognitive and emotional responses to DCIS, with White women generally reporting a better understanding of their diagnosis and treatment, and Latinas reporting more distress. Regardless of ethnicity, women with DCIS preferred that physicians discuss treatment options and attend to their informational and emotional needs. Satisfaction was associated with adequate information, expediency of care, and physicians' sensitivity to patients' emotional needs.

Authors
Nápoles-Springer, AM; Livaudais, JC; Bloom, J; Hwang, S; Kaplan, CP
MLA Citation
Nápoles-Springer, Anna M., et al. “Information exchange and decision making in the treatment of Latina and white women with ductal carcinoma in situ..” J Psychosoc Oncol, vol. 25, no. 4, 2007, pp. 19–36. Pubmed, doi:10.1300/J077v25n04_02.
PMID
18032263
Source
pubmed
Published In
Journal of Psychosocial Oncology
Volume
25
Issue
4
Publish Date
2007
Start Page
19
End Page
36
DOI
10.1300/J077v25n04_02

Total Skin-Sparing Mastectomy Without Preservation of the Nipple-Areola Complex

Authors
Hwang, ES; Esserman, LJ
MLA Citation
Hwang, E. S., and L. J. Esserman. Total Skin-Sparing Mastectomy Without Preservation of the Nipple-Areola Complex. Vol. 17, 2006, pp. 251–52. Scopus, doi:10.1016/S1043-321X(06)80511-4.
Source
scopus
Volume
17
Publish Date
2006
Start Page
251
End Page
252
DOI
10.1016/S1043-321X(06)80511-4

Magnetic resonance imaging captures the biology of ductal carcinoma in situ.

PURPOSE: Magnetic resonance imaging (MRI) is an important tool for characterizing invasive breast cancer but has proven to be more challenging in the setting of ductal carcinoma in situ (DCIS). We investigated whether MRI features of DCIS reflect differences in biology and pathology. PATIENTS AND METHODS: Forty five of 100 patients with biopsy-proven DCIS who underwent MRI and had sufficient tissue to be characterized by pathologic (nuclear grade, presence of comedo necrosis, size, and density of disease) and immunohistochemical (IHC) findings (proliferation, Ki67; angiogenesis, CD34; and inflammation, CD68). Pathology and MRI features (enhancement patterns, distribution, size, and density) were analyzed using pairwise and canonical correlations. RESULTS: Histopathologic and IHC variables correlated with MRI features (r = 0.73). The correlation was largely due to size, density (by either MRI or pathology), and inflammation (P < .05). Most small focal masses were estrogen receptor-positive. MRI enhancement patterns that were clumped were more likely than heterogeneous patterns to be high-grade lesions. Homogenous lesions were large, high grade, and rich in macrophages. Presence of comedo necrosis and size could be distinguished on MRI (P < .05). MRI was most likely to over-represent the size of less dense, diffuse DCIS lesions. CONCLUSION: The heterogeneous presentation of DCIS on MRI reflects underlying histopathologic differences.

Authors
Esserman, LJ; Kumar, AS; Herrera, AF; Leung, J; Au, A; Chen, Y-Y; Moore, DH; Chen, DF; Hellawell, J; Wolverton, D; Hwang, ES; Hylton, NM
MLA Citation
Esserman, Laura J., et al. “Magnetic resonance imaging captures the biology of ductal carcinoma in situ..” J Clin Oncol, vol. 24, no. 28, Oct. 2006, pp. 4603–10. Pubmed, doi:10.1200/JCO.2005.04.5518.
PMID
17008702
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
24
Issue
28
Publish Date
2006
Start Page
4603
End Page
4610
DOI
10.1200/JCO.2005.04.5518

Surgical management of hepatic breast cancer metastases: Commentary

Authors
Golshan, M; Iglehart, JD; Hwang, ES; Esserman, LJ; Kooby, DA
MLA Citation
Golshan, M., et al. “Surgical management of hepatic breast cancer metastases: Commentary.” Oncology, vol. 19, no. 12, 1 Dec. 2005, pp. 1587–96.
Source
scopus
Published In
Oncology (Williston Park, N.Y.)
Volume
19
Issue
12
Publish Date
2005
Start Page
1587
End Page
1596

Erratum: The effect of sentinel node tumor burden on non-sentinel node status and recurrence rates in breast cancer (Annals of Surgical Oncology (September 2005) 12 (9) (705-711) DOI: 10.1245/ASO.2005.08.020)

Authors
Fan, YG; Tan, YY; Wu, CT; Treseler, P; Lu, Y; Chan, CW; Hwang, S; Ewing, C; Esserman, L; Morita, E; Leong, SPL
MLA Citation
Fan, Y. G., et al. “Erratum: The effect of sentinel node tumor burden on non-sentinel node status and recurrence rates in breast cancer (Annals of Surgical Oncology (September 2005) 12 (9) (705-711) DOI: 10.1245/ASO.2005.08.020).” Annals of Surgical Oncology, vol. 12, no. 11, 1 Nov. 2005. Scopus, doi:10.1245/ASO.2005.08.513.
Source
scopus
Published In
Annals of Surgical Oncology
Volume
12
Issue
11
Publish Date
2005
Start Page
952
DOI
10.1245/ASO.2005.08.513

The effect of sentinel node tumor burden on non-sentinel node status and recurrence rates in breast cancer.

BACKGROUND: Routine axillary lymph node dissection (ALND) after selective sentinel lymphadenectomy (SSL) in the treatment of breast cancer remains controversial. We sought to determine the need for routine ALND by exploring the relationship between sentinel lymph node (SLN) and non-SLN (NSLN) status. We also report our experience with disease relapse in the era of SSL and attempt to correlate this with SLN tumor burden. METHODS: This was a retrospective study of 390 patients with invasive breast cancer treated at a single institution who underwent successful SSL from November 1997 to November 2002. RESULTS: Of the 390 patients, 115 received both SSL and ALND. The percentage of additional positive NSLNs in the SLN-positive group (34.2%) was significantly higher than in the SLN-negative group (5.1%; P = .0004). The SLN macrometastasis group had a significantly higher rate of positive NSLNs (39.7%) compared with the SLN-negative group (5.1%; P = .0001). Sixteen patients developed recurrences during follow-up, including 6.1% of SLN-positive and 3.3% of SLN-negative patients. Among the SLN macrometastasis group, 8.7% had recurrence, compared with 2.2% of SLN micrometastases over a median follow-up period of 31.1 months. One regional failure developed out of 38 SLN-positive patients who did not undergo ALND. CONCLUSIONS: ALND is recommended for patients with SLN macrometastasis because of a significantly higher incidence of positive NSLNs. Higher recurrence rates are also seen in these patients. However, the role of routine ALND in patients with a low SLN tumor burden remains to be further determined by prospective randomized trials.

Authors
Fan, Y-G; Tan, Y-Y; Wu, C-T; Treseler, P; Lu, Y; Chan, C-W; Hwang, S; Ewing, C; Esserman, L; Morita, E; Leong, SPL
MLA Citation
Fan, Yang-Guo, et al. “The effect of sentinel node tumor burden on non-sentinel node status and recurrence rates in breast cancer..” Ann Surg Oncol, vol. 12, no. 9, Sept. 2005, pp. 705–11. Pubmed, doi:10.1245/ASO.2005.08.020.
PMID
16079953
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
12
Issue
9
Publish Date
2005
Start Page
705
End Page
711
DOI
10.1245/ASO.2005.08.020

Primary tumor characteristics predict sentinel lymph node macrometastasis in breast cancer.

Selective sentinel lymphadenectomy (SSL) is rapidly becoming the standard of care in the surgical management of patients with early breast cancer. Sentinel lymph node macrometastasis has been well documented in the literature to have a higher risk of nonsentinel node tumor involvement when compared to micrometastasis. The aim of our study was to determine the primary tumor characteristics associated with sentinel node macrometastasis that will allow us to preoperatively determine this subgroup of patients at risk. This study was a retrospective review of 644 patients who underwent successful SSL as part of their surgical treatment of breast cancer at the University of California San Francisco Carol Franc Buck Breast Care Center from November 1997 to August 2003. All patients underwent preoperative lymphoscintigraphy followed by wide excision or mastectomy and sentinel lymphadenectomy with or without axillary lymph node dissection. One hundred twenty-two patients had positive sentinel nodes on histology. Micrometastasis was present in 43 of these patients and macrometastasis in the remaining 79. Statistical analysis showed that a tumor size greater than 15 mm, poor tubule formation by the tumor cells, and lymphovascular invasion were significantly associated with sentinel node macrometastasis. A high mitotic count showed a trend but was not significant in our study. Patients with a tumor size greater than 15 mm, poor tubule formation, and lymphovascular invasion are at risk of having sentinel node macrometastasis. These patients can be identified preoperatively based on imaging and biopsy criteria, allowing the option of selective intraoperative pathologic evaluation of the sentinel node and immediate completion axillary dissection as necessary.

Authors
Tan, Y-Y; Wu, C-T; Fan, Y-G; Hwang, S; Ewing, C; Lane, K; Esserman, L; Lu, Y; Treseler, P; Morita, E; Leong, SPL
MLA Citation
Tan, Yah-Yuen, et al. “Primary tumor characteristics predict sentinel lymph node macrometastasis in breast cancer..” Breast J, vol. 11, no. 5, Sept. 2005, pp. 338–43. Pubmed, doi:10.1111/j.1075-122X.2005.00043.x.
PMID
16174155
Source
pubmed
Published In
Breast Journal
Volume
11
Issue
5
Publish Date
2005
Start Page
338
End Page
343
DOI
10.1111/j.1075-122X.2005.00043.x

Ratio of positive to total number of sentinel nodes predicts nonsentinel node status in breast cancer patients.

Selective sentinel lymphadenectomy (SSL) has replaced axillary lymph node dissection (ALND) for many patients with early breast cancer and negative sentinel lymph nodes (SLNs). Yet many patients with a positive SLN are undergoing unnecessary ALND, as no further disease is found in the axilla. The aim of our study was to determine factors associated with additional positive lymph nodes in the axilla in patients who have a positive SLN. This was a retrospective study of patients undergoing SSL with ALND as part of their treatment for breast cancer at a single institution from November 1997 to August 2003. Only patients with one or more positive SLNs were selected for this study. There were 86 patients who fit our study criteria. Of these, 38% had further positive lymph nodes upon ALND. More than one positive SLN and a ratio of positive SLNs to total SLNs of greater than 0.5 were found to be predictors for additional axillary nodal involvement in both univariate and multivariate analyses. The number of positive SLNs and the ratio of positive SLNs to total SLNs is an indication of total tumor burden in the sentinel nodes and may be a reflection of the propensity of the tumor for further lymphatic invasion in the axillary basin.

Authors
Tan, Y-Y; Fan, Y-G; Lu, Y; Hwang, S; Ewing, C; Esserman, L; Morita, E; Treseler, P; Leong, SPL
MLA Citation
Tan, Yah-Yuen, et al. “Ratio of positive to total number of sentinel nodes predicts nonsentinel node status in breast cancer patients..” Breast J, vol. 11, no. 4, July 2005, pp. 248–53. Pubmed, doi:10.1111/j.1075-122X.2005.21633.x.
PMID
15982390
Source
pubmed
Published In
Breast Journal
Volume
11
Issue
4
Publish Date
2005
Start Page
248
End Page
253
DOI
10.1111/j.1075-122X.2005.21633.x

Innovations in breast cancer care

PURPOSE: To examine the treatment of breast cancer from a historic perspective and explore current therapies and innovations in diagnosis and treatment. EPIDEMIOLOGY: In 2003, 212 600 new cases of breast cancer were diagnosed, and it is estimated that more than 40 000 of those cases will be fatal. The probability of developing invasive breast cancer is age-dependent, ranging from a 1 in 225 (0.44%) chance for women younger than 39 years to a 1 in 14 (7.02%) chance for women aged 60 through 79, with an overall 1 in 8 (12.83%) lifetime risk. REVIEW SUMMARY: From early in recorded history, women and their physicians have been plagued by breast cancer. Currently, breast cancer remains a leading cancer-related cause of death in women, second only to lung cancer. The treatment paradigm has shifted from one mandating radical excision of the breast and all surrounding tissue, to a more systemic view whereby as much breast tissue as possible is conserved and adjuvant therapy is offered to prevent metastasis. Advances in treatment have accelerated over the last few decades and have led and will continue to lead to significant improvements in mortality and morbidity. This article examines an approach to breast cancer management that considers the specific circumstances of each individual woman, guided by tumor biology, age, competing risks of death from other comorbidities, and personal preferences in which survivorship issues have assumed tremendous importance. Finally, future directions in breast cancer care are discussed. TYPE OF AVAILABLE EVIDENCE: Randomized-controlled trials, prospective cohort studies, systematic reviews. GRADE OF AVAILABLE EVIDENCE: Good to excellent. CONCLUSION: Physicians and patients now may select from a myriad of treatments for breast cancer, including surgery (mastectomy vs lumpectomy), radiation therapy, chemotherapy, hormonal therapy, and other biologically targeted therapies. In the future, molecular and imaging markers in combination with clinical parameters will help individually characterize breast cancer type, predict response to therapy, determine prognosis, and ultimately dictate the informed treatment choices women make in conjunction with their physicians.

Authors
Esserman, L; Lane, KT; Ewing, CA; Hwang, ES
MLA Citation
Esserman, L., et al. Innovations in breast cancer care. Vol. 5, 2005, pp. 294–305.
Source
scopus
Volume
5
Publish Date
2005
Start Page
294
End Page
305

MRI measurements of breast tumor volume predict response to neoadjuvant chemotherapy and recurrence-free survival.

OBJECTIVE: The purpose of this study was to assess the value of MRI measurements of breast tumor size for predicting recurrence-free survival (RFS) in patients undergoing neoadjuvant (preoperative) chemotherapy and to compare the predictive value of MRI with that of established prognostic indicators. SUBJECTS AND METHODS: The study included 62 patients undergoing neoadjuvant chemotherapy. The longest diameter and volume of each tumor were measured on MRI before and after one and four cycles of treatment. Change in diameter on clinical examination, tumor size at pathology, and the number of positive nodes were determined. Each measure of tumor extent was assessed for the ability to predict RFS. RESULTS: Univariate Cox analysis showed initial MRI volume was the strongest predictor of RFS (p = 0.002). Final change in MRI volume (p = 0.015) was more predictive than change in diameter on MRI (p = 0.077) or clinical examination (p = 0.27). Initial diameter on MRI (p = 0.003) and clinical examination (p = 0.033), tumor size at pathology (p = 0.016), and number of positive nodes (p = 0.045) were also significantly predictive of RFS. Early change in MRI volume (p = 0.071) and diameter (p = 0.081) after one chemotherapy cycle showed trends of association with RFS. Multivariate analysis showed initial MRI volume (p = 0.005) and final change in MRI volume (p = 0.003) were significant independent predictors. CONCLUSION: MRI tumor volume was more predictive of RFS than tumor diameter, suggesting that volumetric changes measured using MRI may provide a more sensitive assessment of treatment efficacy.

Authors
Partridge, SC; Gibbs, JE; Lu, Y; Esserman, LJ; Tripathy, D; Wolverton, DS; Rugo, HS; Hwang, ES; Ewing, CA; Hylton, NM
MLA Citation
Partridge, Savannah C., et al. “MRI measurements of breast tumor volume predict response to neoadjuvant chemotherapy and recurrence-free survival..” Ajr Am J Roentgenol, vol. 184, no. 6, June 2005, pp. 1774–81. Pubmed, doi:10.2214/ajr.184.6.01841774.
PMID
15908529
Source
pubmed
Published In
Ajr. American Journal of Roentgenology
Volume
184
Issue
6
Publish Date
2005
Start Page
1774
End Page
1781
DOI
10.2214/ajr.184.6.01841774

Clinical application of array-based comparative genomic hybridization to define the relationship between multiple synchronous tumors.

Array-based comparative genomic hybridization (CGH) is a technique that allows genome wide screening of gains and losses in DNA copy number. In cases where multiple tumors are encountered, this genetic technique may prove useful in differentiating new primary tumors from recurrences. In this case report, we used array-based CGH to examine the genomic relationships among two leiomyosarcomas and two breast cancers in the same patient, three of which were diagnosed synchronously. Array-based CGH was performed on the four tumor samples using random prime amplified microdissected DNA. Samples were hybridized onto bacterial artificial chromosome arrays composed of approximately 2400 clones. Patterns of alterations within the tumors were compared and genetic alterations among the leiomyosarcomas and breast lesions were found. Overall, three distinct genetic profiles were observed. While the two leiomyosarcomas shared a similar pattern of genetic alterations, the two invasive breast lesions did not. The nearly identical pattern of genetic alterations belonging to the two metachronous leiomyosarcomas confirmed metastatic recurrence while the two different genetic profiles of the invasive ductal carcinomas suggest that the two lesions represented two distinct foci of multifocal disease rather than clonal extension of the primary tumor. We conclude that genetic analysis by array-based CGH can clearly elucidate the relationships between multiple tumors and may potentially serve as an important clinical tool.

Authors
Wa, CV; DeVries, S; Chen, YY; Waldman, FM; Hwang, ES
MLA Citation
Wa, Chrystal V., et al. “Clinical application of array-based comparative genomic hybridization to define the relationship between multiple synchronous tumors..” Mod Pathol, vol. 18, no. 4, Apr. 2005, pp. 591–97. Pubmed, doi:10.1038/modpathol.3800332.
PMID
15696129
Source
pubmed
Published In
Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc
Volume
18
Issue
4
Publish Date
2005
Start Page
591
End Page
597
DOI
10.1038/modpathol.3800332

Development of a novel method for measuring in vivo breast epithelial cell proliferation in humans.

Cell proliferation plays an important role in all stages of carcinogenesis. Currently, no safe, direct, in vivo method of measuring breast epithelial cell (BEC) proliferation rates in humans exists. Static immunohistochemical markers of cell proliferation, such as Ki-67 and PCNA indices, have technical limitations including high inter-lab variability, inaccuracy in the presence of agents that cause G1/S cell cycle block and inadequate sensitivity in post-menopausal women with low BEC proliferation rates. We describe here a safe, direct method of measuring BEC proliferation rates in vivo in women using heavy water ((2)H(2)O) labeling coupled with mass spectrometric analysis. Proliferation of normal and tumor BEC was measured from breast tissue biopsies in women undergoing mastectomy (n = 11) and normal BEC from healthy volunteers (n = 16). Women took heavy water (50-150 ml per day) for 1-4 weeks. Pre-menopausal women had significantly higher proliferation rates than post-menopausal women (0.7 +/- 0.1 versus 0.2 +/- 0.1 new cells per day, respectively), and tumor BEC had different proliferation rates than normal BEC from the same breast. The method is analytically reproducible and remains sensitive in the range of low proliferation rates. In summary, this novel method of measuring BEC proliferation in vivo holds promise for assessing the effects of anti-proliferative chemopreventive and chemotherapeutic agents.

Authors
Misell, LM; Hwang, ES; Au, A; Esserman, L; Hellerstein, MK
MLA Citation
Misell, Lisa M., et al. “Development of a novel method for measuring in vivo breast epithelial cell proliferation in humans..” Breast Cancer Res Treat, vol. 89, no. 3, Feb. 2005, pp. 257–64. Pubmed, doi:10.1007/s10549-004-2228-5.
PMID
15754124
Source
pubmed
Published In
Breast Cancer Research and Treatment
Volume
89
Issue
3
Publish Date
2005
Start Page
257
End Page
264
DOI
10.1007/s10549-004-2228-5

Array-based comparative genomic hybridization from formalin-fixed, paraffin-embedded breast tumors.

Identification of prognostic and predictive genomic markers requires long-term clinical follow-up of patients. Extraction of high-quality DNA from archived formalin-fixed, paraffin-embedded material is essential for such studies. Of particular importance is a robust reproducible method of whole genome amplification for small tissue samples. This is especially true for high-resolution analytical approaches because different genomic regions and sequences may amplify differentially. We have tested a number of protocols for DNA amplification for array-based comparative genomic hybridization (CGH), in which relative copy number of the entire genome is measured at 1 to 2 mb resolution. Both random-primed amplification and degenerate oligonucleotide-primed amplification approaches were tested using varying amounts of fresh and paraffin-extracted normal and breast tumor input DNAs. We found that random-primed amplification was clearly superior to degenerate oligonucleotide-primed amplification for array-based CGH. The best quality and reproducibility strongly depended on accurate determination of the amount of input DNA using a quantitative polymerase chain reaction-based method. Reproducible and high-quality results were attained using 50 ng of input DNA, and some samples yielded quality results with as little as 5 ng input DNA. We conclude that random-primed amplification of DNA isolated from paraffin sections is a robust and reproducible approach for array-based CGH analysis of archival tumor samples.

Authors
Devries, S; Nyante, S; Korkola, J; Segraves, R; Nakao, K; Moore, D; Bae, H; Wilhelm, M; Hwang, S; Waldman, F
MLA Citation
Devries, Sandy, et al. “Array-based comparative genomic hybridization from formalin-fixed, paraffin-embedded breast tumors..” J Mol Diagn, vol. 7, no. 1, Feb. 2005, pp. 65–71. Pubmed, doi:10.1016/S1525-1578(10)60010-4.
PMID
15681476
Source
pubmed
Published In
The Journal of Molecular Diagnostics
Volume
7
Issue
1
Publish Date
2005
Start Page
65
End Page
71
DOI
10.1016/S1525-1578(10)60010-4

Safety of immediate transverse rectus abdominis myocutaneous breast reconstruction for patients with locally advanced disease.

HYPOTHESIS: Immediate transverse rectus abdominis myocutaneous breast reconstruction combined with postoperative radiation therapy after mastectomy is safe and effective. DESIGN: Retrospective case series. SETTING: University-based teaching hospital. PATIENTS: From January 1, 1996, through December 31, 2003, 252 patients underwent mastectomy and immediate transverse rectus abdominis myocutaneous flap reconstruction. Of those, 35 patients received postoperative radiation therapy (stage I, n = 1; II, n = 17; III, n = 15; IV, n = 2). Age range was 29 to 72 years (mean, 49.5 years). Follow-up was 1 to 8 years (mean, 48 months). MAIN OUTCOME MEASURES: Flap loss, fat necrosis, flap volume loss, adjuvant treatment delay, and need for additional surgery. RESULTS: The rate of flap survival was 100%. Median operative time was 5.5 hours. Average hospital stay was 5.2 days. Fat necrosis occurred in 3 patients, with volume loss requiring additional surgery in 2 patients (6%). Postoperative adjuvant therapy was not significantly delayed (median interval, 32 days). With a median follow-up of 48 months, local recurrence was present in only 1 patient (3%), who underwent successful local salvage, and distant metastasis occurred in 4 patients (11%). CONCLUSIONS: Immediate transverse rectus abdominis myocutaneous breast reconstruction followed by radiation therapy is safe, with minimal morbidity and no significant change in tissue volume. Complications tend to be minor, not delaying adjuvant therapy. Immediate breast reconstruction should be considered after mastectomy, despite the need for postoperative radiation therapy.

Authors
Foster, RD; Hansen, SL; Esserman, LJ; Hwang, ES; Ewing, C; Lane, K; Anthony, JP
MLA Citation
Foster, Robert D., et al. “Safety of immediate transverse rectus abdominis myocutaneous breast reconstruction for patients with locally advanced disease..” Arch Surg, vol. 140, no. 2, Feb. 2005, pp. 196–98. Pubmed, doi:10.1001/archsurg.140.2.196.
PMID
15724003
Source
pubmed
Published In
Archives of Surgery (Chicago, Ill. : 1960)
Volume
140
Issue
2
Publish Date
2005
Start Page
196
End Page
198
DOI
10.1001/archsurg.140.2.196

Internal mammary sentinel lymph node mapping for invasive breast cancer: implications for staging and treatment.

The optimal staging and treatment of the internal mammary nodes (IMNs) among patients with invasive breast cancer (IBC) is controversial. Although medial tumors have been reported to more commonly drain to IMNs, other variables predictive for IMN drainage may help identify those patients who may benefit from further IMN assessment. Factors associated with IMN drainage were analyzed among 141 patients who underwent lymphatic mapping and selective sentinel lymphadenectomy using intradermal injection (ID) or peritumoral (PT) injection. Fourteen of 83 patients (17%) receiving PT injections had IMN drainage, compared to none among the 58 patients who underwent ID injection alone (p = 0.0004). There were no differences in patient or tumor variables detected between the two groups. Among patients receiving PT injections, no factors examined were significantly associated with IMN drainage on univariate analysis. Using the multivariate logistic regression model, palpable disease was the most important factor associated with IMN drainage (risk ratio [RR] = 6.02; 95% confidence interval [CI] 0.64-56.34; p = 0.05). In addition, lymphatic/vascular invasion (LVI) and age less than 50 years were associated with IMN drainage (RR = 6.17; 95% CI 1.02-37.50; p = 0.09 and RR = 2.94; 95% CI 0.82-10.49; p = 0.09, respectively). IMN drainage occurred in a significant proportion of patients after PT injection, but not ID injection. In the final model, palpable disease was the most important factor associated with IMN drainage; LVI and age less than 50 years were of borderline significance. These factors may aid in the selection of patients who might benefit from further staging or treatment of the IMNs.

Authors
Park, C; Seid, P; Morita, E; Iwanaga, K; Weinberg, V; Quivey, J; Hwang, ES; Esserman, LJ; Leong, SPL
MLA Citation
Park, Catherine, et al. “Internal mammary sentinel lymph node mapping for invasive breast cancer: implications for staging and treatment..” Breast J, vol. 11, no. 1, Jan. 2005, pp. 29–33. Pubmed, doi:10.1111/j.1075-122X.2005.21527.x.
PMID
15647075
Source
pubmed
Published In
Breast Journal
Volume
11
Issue
1
Publish Date
2005
Start Page
29
End Page
33
DOI
10.1111/j.1075-122X.2005.21527.x

Risk factors for estrogen receptor-positive breast cancer.

HYPOTHESIS: Some risk factors associated with breast cancer may be more predictive of estrogen receptor (ER)- positive than ER-negative tumors. DESIGN: Survey of patients enrolled in a study of breast cancer risk factors. SETTING: Community population in a northern California county. PATIENTS: A total of 234 individuals diagnosed as having breast cancer between July 1, 1997, and June 30, 1999, reporting Marin County, California, residence and participating in a questionnaire regarding exposure to breast cancer risk factors. MAIN OUTCOME MEASURE: Diagnosis of ER-positive vs ER-negative breast cancer. RESULTS: Comparison between ER-positive and ER-negative cases showed several factors predictive of ER-positive tumors. In a multivariate model, years of hormone therapy use remained the most significant predictor of ER-positive disease. CONCLUSIONS: Patients diagnosed as having ER-positive breast cancer were more likely to have undergone hormone therapy. The excess of ER-positive breast cancers reported in Marin County could, therefore, in part, be related to hormone therapy.

Authors
Hwang, ES; Chew, T; Shiboski, S; Farren, G; Benz, CC; Wrensch, M
MLA Citation
Hwang, E. Shelley, et al. “Risk factors for estrogen receptor-positive breast cancer..” Arch Surg, vol. 140, no. 1, Jan. 2005, pp. 58–62. Pubmed, doi:10.1001/archsurg.140.1.58.
PMID
15655207
Source
pubmed
Published In
Archives of Surgery (Chicago, Ill. : 1960)
Volume
140
Issue
1
Publish Date
2005
Start Page
58
End Page
62
DOI
10.1001/archsurg.140.1.58

[18F]fluorodeoxyglucose-positron emission tomography in patients with medulloblastoma.

OBJECTIVE: We evaluated the [(18)F]fluorodeoxyglucose (FDG) accumulation during positron emission tomography (PET) in patients with medulloblastoma and examined the relationship of intensity of uptake with patient outcome after the initial scan. METHODS: Magnetic resonance imaging and FDG-PET scans of brain and spine were used to assess FDG uptake by visual grade (qualitative analysis) and metabolic activity ratios (T(max)/G(mean) and T(max)/W(mean)). Patients were divided into two groups based on either confirmation of tumor by biopsy and/or death resulting from progressive disease after the initial FDG-PET scan (Group A) or no intervention for the suspected lesion shown on magnetic resonance imaging after the initial FDG-PET scan but currently alive without evidence of disease (Group B). RESULTS: Twenty-two patients with either recurrent (n = 21) or newly diagnosed (n = 1) medulloblastoma underwent brain (n = 18) or whole-body (n = 4) FDG-PET scans after magnetic resonance imaging evidence of suspected tumor. The median qualitative analysis was 3 (range, 0-4) in 17 Group A patients compared with 0 (range, 0-1) in 5 Group B patients (P = 0.0003). The mean T(max)/G(mean) and T(max)/W(mean) ratios for 16 Group A patients were 1.3 (range, 0.1-3.8) and 2.10 (range, 0.4-5.2), respectively, compared with 0.80 (range, 0.20-1.5) and 1.3 (range, 0.5-1.9) in 5 Group B patients (P = 0.2 for both parameters, not significant). There was a significant negative correlation between increased FDG uptake and survival. Higher qualitative analysis and T(max)/W(mean) were associated with significantly poorer 2-year overall survival after the initial scan (71% versus 15% for qualitative analysis grade of <3 versus > or =3, P = 0.001; 46% versus 0% for T(max)/W(mean) < or =2.5 versus >2.5, P = 0.004). CONCLUSION: Increased FDG uptake is observed in medulloblastoma and is correlated negatively with survival.

Authors
Gururangan, S; Hwang, E; Herndon, JE; Fuchs, H; George, T; Coleman, RE
MLA Citation
Gururangan, Sridharan, et al. “[18F]fluorodeoxyglucose-positron emission tomography in patients with medulloblastoma..” Neurosurgery, vol. 55, no. 6, Dec. 2004, pp. 1280–88. Pubmed, doi:10.1227/01.neu.0000143027.41632.2b.
PMID
15574210
Source
pubmed
Published In
Neurosurgery
Volume
55
Issue
6
Publish Date
2004
Start Page
1280
End Page
1288
DOI
10.1227/01.neu.0000143027.41632.2b

Accuracy of selective sentinel lymphadenectomy after neoadjuvant chemotherapy: effect of clinical node status at presentation.

BACKGROUND: Both neoadjuvant chemotherapy and selective sentinel lymphadenectomy (SSL) are increasingly being used in treating primary breast cancer. It is important to determine whether SSL can be used after neoadjuvant chemotherapy and whether clinical node status at presentation affects accuracy of SSL. STUDY DESIGN: Between 1995 and 2003, 53 evaluable cases of invasive breast cancer were treated with neoadjuvant chemotherapy followed by SSL and completion axillary node dissection. The accuracy of SSL and the number of failed SSLs were assessed in the entire group and in the subset that were clinically node positive at presentation. RESULTS: The sensitivity of SSL was 96%, the negative predictive value was 96%, and the sentinel node identification rate was 94%. Of the 53 evaluable patients, 23 had clinically node-positive disease at presentation (43%) and the remainder were clinically node negative (57%). Of the successfully completed SSL, the status of the sentinel lymph node corresponded to that of overall axillary status in 49 of 50 patients (accuracy rate 98%). Two of the 23 patients with clinically node-positive disease at presentation had unsuccessful SSL. Of the remaining 21 patients with a clinically positive axilla before systemic therapy, a false-negative SSL result occurred in 1 patient (accuracy 95%, sensitivity 91%). CONCLUSIONS: Selective sentinel lymphadenectomy after neoadjuvant chemotherapy is both feasible and accurate. Although early reports found a lower performance of SSL after neoadjuvant chemotherapy, this study suggests reevaluation of the current practice of full axillary lymph node dissection in this setting, particularly in those patients who are clinically node negative at presentation.

Authors
Lang, JE; Esserman, LJ; Ewing, CA; Rugo, HS; Lane, KT; Leong, SP; Hwang, ES
MLA Citation
Lang, Julie E., et al. “Accuracy of selective sentinel lymphadenectomy after neoadjuvant chemotherapy: effect of clinical node status at presentation..” J Am Coll Surg, vol. 199, no. 6, Dec. 2004, pp. 856–62. Pubmed, doi:10.1016/j.jamcollsurg.2004.08.023.
PMID
15555967
Source
pubmed
Published In
Journal of the American College of Surgeons
Volume
199
Issue
6
Publish Date
2004
Start Page
856
End Page
862
DOI
10.1016/j.jamcollsurg.2004.08.023

Patterns of chromosomal alterations in breast ductal carcinoma in situ.

PURPOSE: Ductal carcinoma in situ (DCIS) is thought to be a nonobligate precursor of invasive cancer. Genomic changes specific to pure DCIS versus invasive cancer, as well as alterations unique to individual DCIS subtypes, have not been fully defined. EXPERIMENTAL DESIGN: Chromosomal copy number alterations were examined by comparative genomic hybridization in 34 cases of pure DCIS and compared with 12 cases of paired synchronous DCIS and invasive ductal cancer, as well as to 146 additional cases of invasive breast cancer of ductal or lobular histology. Genomic differences between high-grade and low/intermediate-grade DCIS, as well as between pure DCIS and invasive cancer, were identified. RESULTS: Pure DCIS showed almost the same degree of chromosomal instability as invasive ductal cancers. A higher proportion of low/intermediate-grade versus high-grade DCIS had loss of 16q (65 versus 12%, respectively; P = 0.002). When compared with lower grade DCIS, high-grade DCIS exhibited more frequent gain of 17q (65 versus 41%; P = 0.15) and higher frequency loss of 8p (77 versus 41%; P = 0.04). Chromosomal alterations in those cases with synchronous DCIS and invasive ductal cancer showed a high degree of shared changes within the two components. CONCLUSIONS: DCIS is genetically advanced, showing a similar degree of chromosomal alterations as invasive ductal cancer. The pattern of alterations differed between high- and low/intermediate-grade DCIS, supporting a model in which different histological grades of DCIS are associated with distinct genomic changes. These regions of chromosomal alterations may be potential targets for treatment and/or markers of prognosis.

Authors
Hwang, ES; DeVries, S; Chew, KL; Moore, DH; Kerlikowske, K; Thor, A; Ljung, B-M; Waldman, FM
MLA Citation
Hwang, E. Shelley, et al. “Patterns of chromosomal alterations in breast ductal carcinoma in situ..” Clin Cancer Res, vol. 10, no. 15, Aug. 2004, pp. 5160–67. Pubmed, doi:10.1158/1078-0432.CCR-04-0165.
PMID
15297420
Source
pubmed
Published In
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Volume
10
Issue
15
Publish Date
2004
Start Page
5160
End Page
5167
DOI
10.1158/1078-0432.CCR-04-0165

Clonality of lobular carcinoma in situ and synchronous invasive lobular carcinoma.

BACKGROUND: Lobular carcinoma in situ (LCIS) of the breast is considered a marker for an increased risk of carcinoma in both breasts. However, the frequent association of LCIS with invasive lobular carcinoma (ILC) suggests a precursor-product relation. The possible genomic relation between synchronous LCIS and ILC was analyzed using the technique of array-based comparative genomic hybridization (CGH). METHODS: Twenty-four samples from the University of California-San Francisco pathology archives that contained synchronous LCIS and ILC were identified. Array CGH was performed using random primer-amplified microdissected DNA. Samples were hybridized onto bacterial artificial chromosome arrays composed of approximately 2400 clones. Patterns of alterations within synchronous LCIS and ILC were compared. RESULTS: A substantial proportion of the genome was altered in samples of both LCIS and ILC. The most frequent alterations were gain of 1q and loss of 16q, both of which usually occurred as whole-arm changes. Smaller regions of gain and loss were seen on other chromosome arms. Fourteen samples of LCIS were related more to their paired samples of ILC than to any other ILC, as demonstrated by a weighted similarity score. CONCLUSIONS: LCIS and ILC are neoplastic lesions that demonstrate a range of genomic alterations. In the current study, the genetic relation between synchronous LCIS and ILC suggested clonality in a majority of the paired specimens. These data were consistent with a progression pathway from LCIS to ILC. The authors conclude that LCIS, which is known to be a marker for an environment that is permissive of neoplasia, may itself represent a precursor to invasive carcinoma.

Authors
Hwang, ES; Nyante, SJ; Yi Chen, Y; Moore, D; DeVries, S; Korkola, JE; Esserman, LJ; Waldman, FM
MLA Citation
Hwang, E. Shelley, et al. “Clonality of lobular carcinoma in situ and synchronous invasive lobular carcinoma..” Cancer, vol. 100, no. 12, June 2004, pp. 2562–72. Pubmed, doi:10.1002/cncr.20273.
PMID
15197797
Source
pubmed
Published In
Cancer
Volume
100
Issue
12
Publish Date
2004
Start Page
2562
End Page
2572
DOI
10.1002/cncr.20273

Array-based comparative genomic hybridization of ductal carcinoma in situ and synchronous invasive lobular cancer.

It has been increasingly recognized that ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS) and invasive cancer of the breast are often closely associated with one another. However, the genomic relationship between these histologically distinct entities has not been well characterized. Refinements in high-resolution comparative genomic hybridization (CGH) techniques allow for a detailed comparison of genomic alterations in synchronously occurring tumors. The following case illustrates how array CGH may be used to better understand whether synchronous neoplasms share a common origin.

Authors
Nyante, SJ; Devries, S; Chen, YY; Hwang, ES
MLA Citation
Nyante, Sarah J., et al. “Array-based comparative genomic hybridization of ductal carcinoma in situ and synchronous invasive lobular cancer..” Hum Pathol, vol. 35, no. 6, June 2004, pp. 759–63. Pubmed, doi:10.1016/j.humpath.2003.11.009.
PMID
15188144
Source
pubmed
Published In
Human Pathology
Volume
35
Issue
6
Publish Date
2004
Start Page
759
End Page
763
DOI
10.1016/j.humpath.2003.11.009

Applying the neoadjuvant paradigm to ductal carcinoma in situ.

Local treatment options for ductal carcinoma in situ (DCIS) are virtually identical to those for early invasive breast cancer, despite the fact that the survival from this condition is much higher. Our ability to more appropriately tailor therapy for DCIS is hampered by a lack of understanding of the natural history of DCIS, our limited ability to predict the rate of progression to invasive cancer and the response to therapy, and the absence of tools to follow patients who have not had invasive treatments. Neoadjuvant therapy, which has been proven to be both safe and effective in tailoring treatments for invasive cancer, could be ideally suited to DCIS. However, neoadjuvant therapy requires that doctors and patients delay surgical treatment that has known benefits. In order to successfully introduce this approach into clinical practice, risk assessment and decision support tools will be needed to help physicians and patients feel comfortable that they are not being exposed to unnecessary or excessive risk. In addition, we need better imaging to track extent and progression of disease. Among the possible benefits of the neoadjuvant approach, we may discover that many lesions are responsive and some even reversible, leaving us with treatments that might be tailored to biology and with important clues for breast cancer prevention in high-risk women.

Authors
Esserman, L; Sepucha, K; Ozanne, E; Hwang, ES
MLA Citation
Esserman, Laura, et al. “Applying the neoadjuvant paradigm to ductal carcinoma in situ..” Ann Surg Oncol, vol. 11, no. 1 Suppl, Jan. 2004, pp. 28S-36S.
PMID
15015707
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
11
Issue
1 Suppl
Publish Date
2004
Start Page
28S
End Page
36S

Neoadjuvant hormonal therapy for ductal carcinoma in situ: trial design and preliminary results.

For some women, the treatment for ductal carcinoma in situ (DCIS) may be even more aggressive than treatments undertaken for early-stage invasive disease. Expectant management is not a tenable alternative, given that in a significant percentage of patients, DCIS eventually progresses to invasive cancer. Nevertheless, if this progression could be halted or reversed with primary medical therapy alone, a significant portion of the 50,000 women diagnosed with DCIS in the United States annually could potentially avoid the morbidity of surgery and radiation for this disease. The most promising therapeutic candidates in this regard are those treatments targeting hormone receptors on breast cancer cells. We have initiated a clinical trial of neoadjuvant hormonal therapy for women with hormone receptor-positive DCIS. We discuss the clinical rationale and study design for this trial and present our preliminary results.

Authors
Hwang, ES; Esserman, L
MLA Citation
Hwang, E. Shelley, and Laura Esserman. “Neoadjuvant hormonal therapy for ductal carcinoma in situ: trial design and preliminary results..” Ann Surg Oncol, vol. 11, no. 1 Suppl, Jan. 2004, pp. 37S-43S.
PMID
15015708
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
11
Issue
1 Suppl
Publish Date
2004
Start Page
37S
End Page
43S

Breast conservation surgery using nipple-areolar resection for central breast cancers.

HYPOTHESIS: Resection of the nipple-areolar complex (NAC) for central breast cancers that involve the nipple or areola, with postoperative radiation therapy, adheres to the oncologic principles established for breast conservation surgery of other breast cancers. Good or excellent cosmetic results can be achieved. The rate of ipsilateral breast recurrence will be similar to that seen with peripheral breast cancers. The indications for breast conservation surgery can be safely extended to include patients with breast cancers that involve the NAC. DESIGN: Retrospective medical record review; follow-up patient questionnaire. SETTING: Community teaching hospital. PATIENTS: Fifteen patients, aged 46 to 88 years, whose central breast cancers involved the NAC precluding preservation of the NAC. INTERVENTIONS: Nipple-areolar complex resection, postoperative radiation therapy. MAIN OUTCOME MEASURES: Ipsilateral breast recurrence, survival, cosmesis. RESULTS: Ten patients had subareolar cancers that directly involved the nipple or areola; 5 patients had Paget disease of the nipple. Average tumor size was 1.6 cm (range, 0.2-3.5 cm). With a mean follow-up of 32 months (range, 4-109 months), there has been only 1 recurrence (7%), which was treated successfully by modified radical mastectomy. All 15 patients are alive and free of disease. Cosmetic results are satisfactory to excellent, as judged by both the patients and the surgeons. CONCLUSIONS: Nipple-areolar complex resection for central subareolar cancers that directly involve the NAC, as well as for Paget disease of the nipple, extends the indications for breast conservation in other areas of the breast, and with acceptable cosmesis.

Authors
Pezzi, CM; Kukora, JS; Audet, IM; Herbert, SH; Horvick, D; Richter, MP
MLA Citation
Pezzi, Christopher M., et al. “Breast conservation surgery using nipple-areolar resection for central breast cancers..” Arch Surg, vol. 139, no. 1, Jan. 2004, pp. 32–37. Pubmed, doi:10.1001/archsurg.139.1.32.
PMID
14718272
Source
pubmed
Published In
Archives of Surgery (Chicago, Ill. : 1960)
Volume
139
Issue
1
Publish Date
2004
Start Page
32
End Page
37
DOI
10.1001/archsurg.139.1.32

Differentiation of lobular versus ductal breast carcinomas by expression microarray analysis.

Invasive lobular and ductal breast tumors have distinct histologies and clinical presentation. Other than altered expression of E-cadherin, little is known about the underlying biology that distinguishes the tumor subtypes. We used cDNA microarrays to identify genes differentially expressed between lobular and ductal tumors. Unsupervised clustering of tumors failed to distinguish between the two subtypes. Prediction analysis for microarrays (PAM) was able to predict tumor type with an accuracy of 93.7%. Genes that were significantly differentially expressed between the two groups were identified by MaxT permutation analysis using t tests (20 cDNA clones and 10 unique genes), significance analysis for microarrays (33 cDNA clones and 15 genes, at an estimated false discovery rate of 2%), and PAM (31 cDNAs and 15 genes). There were 8 genes identified by all three of these related methods (E-cadherin, survivin, cathepsin B, TPI1, SPRY1, SCYA14, TFAP2B, and thrombospondin 4), and an additional 3 that were identified by significance analysis for microarrays and PAM (osteopontin, HLA-G, and CHC1). To validate the differential expression of these genes, 7 of them were tested by real-time quantitative PCR, which verified that they were differentially expressed in lobular versus ductal tumors. In conclusion, specific changes in gene expression distinguish lobular from ductal breast carcinomas. These genes may be important in understanding the basis of phenotypic differences among breast cancers.

Authors
Korkola, JE; DeVries, S; Fridlyand, J; Hwang, ES; Estep, ALH; Chen, Y-Y; Chew, KL; Dairkee, SH; Jensen, RM; Waldman, FM
MLA Citation
Korkola, James E., et al. “Differentiation of lobular versus ductal breast carcinomas by expression microarray analysis..” Cancer Res, vol. 63, no. 21, Nov. 2003, pp. 7167–75.
PMID
14612510
Source
pubmed
Published In
Cancer Research
Volume
63
Issue
21
Publish Date
2003
Start Page
7167
End Page
7175

Integrative tumor board: recurrent breast cancer or new primary? UCSF Osher Center for Integrative Medicine and UCSF Carol Franc Buck Breast Care Center.

Authors
Jacobs, BP; Burns, B; Marya, R; Chapman, J; Stone, B; Hwang, S; Goldman, M; Barrows, K; Hamolsky, D; Sampel, K
MLA Citation
Jacobs, Bradly P., et al. “Integrative tumor board: recurrent breast cancer or new primary? UCSF Osher Center for Integrative Medicine and UCSF Carol Franc Buck Breast Care Center..” Integr Cancer Ther, vol. 2, no. 3, Sept. 2003, pp. 289–300. Pubmed, doi:10.1177/15347354030023014.
PMID
15035894
Source
pubmed
Published In
Integrative Cancer Therapies
Volume
2
Issue
3
Publish Date
2003
Start Page
289
End Page
300
DOI
10.1177/15347354030023014

Magnetic resonance imaging in patients diagnosed with ductal carcinoma-in-situ: value in the diagnosis of residual disease, occult invasion, and multicentricity.

BACKGROUND: Although magnetic resonance imaging (MRI) has been shown to be a sensitive imaging tool for invasive breast cancers, its utility in ductal carcinoma-in-situ (DCIS) of the breast remains controversial. We studied the performance of MRI in patients with known DCIS for assessment of residual disease, occult invasion, and multicentricity to determine the clinical role of MRI in this setting. METHODS: Fifty-one patients with biopsy-proven DCIS underwent contrast-enhanced MRI before surgical treatment. Pre-, early post-, and late postcontrast three-dimensional gradient echo images were obtained and MRI findings were correlated with histopathology. When possible, the performance of MRI and mammography was compared. RESULTS: The accuracy of MRI was 88% in predicting residual disease, 82% in predicting invasive disease, and 90% in predicting multicentricity. The performance of MRI was equivalent in the core biopsy group when compared with the surgical biopsy group. For occult invasion only, MRI and mammography were equivalent. However, overall, MRI was more sensitive and had a higher negative predictive value than mammography. CONCLUSIONS: MRI of DCIS can serve as a useful adjunct to mammography by providing a more accurate assessment of the extent of residual or multicentric disease. The performance of MRI is not significantly affected by antecedent surgical excision. MRI may be particularly valuable if preoperatively negative.

Authors
Hwang, ES; Kinkel, K; Esserman, LJ; Lu, Y; Weidner, N; Hylton, NM
MLA Citation
Hwang, E. Shelley, et al. “Magnetic resonance imaging in patients diagnosed with ductal carcinoma-in-situ: value in the diagnosis of residual disease, occult invasion, and multicentricity..” Ann Surg Oncol, vol. 10, no. 4, May 2003, pp. 381–88.
PMID
12734086
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
10
Issue
4
Publish Date
2003
Start Page
381
End Page
388

Failure to harvest sentinel lymph nodes identified by preoperative lymphoscintigraphy in breast cancer patients.

Selective sentinel lymphadenectomy dissection has been demonstrated to have high predictive value for axillary staging in breast cancer patients. Preoperative lymphoscintigraphy can localize and facilitate the harvesting of sentinel lymph nodes (SNLs) with a high success rate. The failure rate of selective sentinel lymphadenectomy ranges between 2% and 8%. Details of the failures were seldom addressed. This study analyzes the causes of failure to harvest SLNs in spite of positive preoperative lymphoscintigraphy. From November 1997 through November 2000, 201 female patients with histologically confirmed and operable breast carcinoma underwent selective sentinel lymphadenectomy at the University of California, San Francisco (UCSF) Carol Franc Buck Breast Care Center. Among these patients, 183 (91%) received preoperative lymphoscintigraphy to identify axillary lymph nodes. The causes of failure to harvest the SLNs in this group of patients despite successful preoperative lymphoscintigraphy were analyzed. In our series, the failure rate of SLN identification was 7.0% (14/201). The failure rate for our first year was 11.1% (6/54), second year 9.1% (7/77), and third year 1.4% (1/70). The incidence of failure in spite of positive preoperative lymphoscintigraphy was 3.5% (6/170). The shine-through effect of the primary injection site and failure to visualize a blue lymph node were the main reasons for technical failure. Most of these cases occurred during our learning curve of the procedure. The possibility of failure to get the SLN should be explained to patients before surgery. Axillary lymph node dissection (ALND) should be done if selective SLN dissection is not successful.

Authors
Wu, C-T; Morita, ET; Treseler, PA; Esserman, LJ; Hwang, ES; Kuerer, HM; Santos, CL; Leong, SPL
MLA Citation
Wu, Chen-Teng, et al. “Failure to harvest sentinel lymph nodes identified by preoperative lymphoscintigraphy in breast cancer patients..” Breast J, vol. 9, no. 2, Mar. 2003, pp. 86–90.
PMID
12603380
Source
pubmed
Published In
Breast Journal
Volume
9
Issue
2
Publish Date
2003
Start Page
86
End Page
90

Skin-sparing mastectomy and immediate breast reconstruction: a prospective cohort study for the treatment of advanced stages of breast carcinoma.

BACKGROUND: Recent published series demonstrate the safety and effectiveness of skin-sparing mastectomy (SSM) with immediate reconstruction for the treatment of early-stage breast carcinoma. Although several reports have retrospectively evaluated outcomes after breast reconstruction for locally advanced disease (stages IIB and III), no study has specifically considered immediate breast reconstruction after SSM for locally advanced disease. METHODS: From 1996 to 1998, 67 consecutive patients with breast carcinoma underwent SSM with immediate reconstruction and were prospectively observed. From this group of patients, those with locally advanced disease (stage IIB, n = 12; stage III, n = 13) were analyzed separately. Tumor characteristics, adjuvant therapy, type of reconstruction, operative time, complications, hospital stay, and incidence of local recurrence and distant metastasis were noted. RESULTS: Breast reconstruction consisted of a transverse rectus abdominis myocutaneous flap (n = 22) or a latissimus flap plus an implant (n = 4). The median operative time was 5.5 hours; the average hospital stay was 5.2 days. Complications required reoperation in three patients (12%): partial skin flap necrosis in two and partial abdominal skin necrosis in one. Surgery on the opposite breast for symmetry was required in one patient (4%). Postoperative adjuvant therapy was not significantly delayed (median interval, 32 days). With a median length of follow-up of 49.2 months (range, 33-64 months), local recurrence was present in only one patient (4%), with successful local salvage treatment, and distant metastasis was present in four patients (16%). CONCLUSIONS: SSM with immediate reconstruction seems safe and effective and has a low morbidity for patients with advanced stages of breast carcinoma. Local recurrence rates and the incidence of distant metastasis are not increased compared with those of patients who have had modified radical mastectomies without reconstruction.

Authors
Foster, RD; Esserman, LJ; Anthony, JP; Hwang, E-SS; Do, H
MLA Citation
Foster, Robert D., et al. “Skin-sparing mastectomy and immediate breast reconstruction: a prospective cohort study for the treatment of advanced stages of breast carcinoma..” Ann Surg Oncol, vol. 9, no. 5, June 2002, pp. 462–66.
PMID
12052757
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
9
Issue
5
Publish Date
2002
Start Page
462
End Page
466

MRI phenotype is associated with response to doxorubicin and cyclophosphamide neoadjuvant chemotherapy in stage III breast cancer.

BACKGROUND: The preferred management for women with stage II or locally advanced breast cancer (LABC) is neoadjuvant chemotherapy. Pathologic response to chemotherapy has been shown to be an excellent predictor of outcome. Surrogates that can predict pathologic response and outcome will fuel future changes in management. Magnetic resonance imaging (MRI) demonstrates that patients with LABC have distinct tumor patterns. We investigated whether or not these patterns predict response to therapy. METHODS: Thirty-three women who received neoadjuvant doxorubicin and cyclophosphamide chemotherapy for 4 cycles and serial breast MRI scans before and after therapy were evaluated for this study. Response to therapy was measured by change in the longest diameter on the MRI. RESULTS: Five distinct imaging patterns were identified: circumscribed mass, nodular tissue infiltration diffuse tissue infiltration, patchy enhancement, and septal spread. The likelihood of a partial or complete response as measured by change in longest diameter was 77%, 37.5%, 20%, and 25%, respectively. CONCLUSIONS: MRI affords three-dimensional characterization of tumors and has revealed distinct patterns of tumor presentation that predict response. A multisite trial is being planned to combine imaging and genetic information in an effort to better understand and predict response and, ultimately, to tailor therapy and direct the use of novel agents.

Authors
Esserman, L; Kaplan, E; Partridge, S; Tripathy, D; Rugo, H; Park, J; Hwang, S; Kuerer, H; Sudilovsky, D; Lu, Y; Hylton, N
MLA Citation
Esserman, L., et al. “MRI phenotype is associated with response to doxorubicin and cyclophosphamide neoadjuvant chemotherapy in stage III breast cancer..” Ann Surg Oncol, vol. 8, no. 6, July 2001, pp. 549–59.
PMID
11456056
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
8
Issue
6
Publish Date
2001
Start Page
549
End Page
559

Analysis of bone marrow micrometastasis in primary breast cancer: Automated cellular imaging analysis in relation to quantitative RT-PCR and tumor clinicopathologic features

The presence of bone marrow micrometastasis (MM) has been reported to be an adverse prognostic indicator in primary breast cancer, and may be of value in adjuvant therapy decision-making. To date, MM detection has been pursued by a variety of cell-based and molecular methods, and it remains unclear which methodologies are most useful, including recently developed techniques. In a prospective study, we have evaluated MM using novel methods applied to primary breast cancer patients. Methods: We have developed and optimized a highly sensitive cell-based MM assay (cMM) involving multiple antigen immunomagnetic capture (positive selection for MM), anti-cytokeratin immunocytochemical (ICC) staining, and automated cellular imaging (ACIS, ChromaVision Medical Systems, Inc.). The resulting cellular images are immediately available for review by laboratory professionals and pathologists. In addition to this assay, we have developed quantitative RT-PCR for MM-associated mRNAs mammaglobin, PSA, HER2, alternatively spliced HER2, and EGFRvIII. Results: The ICC-based assay has been documented to provide reproducible detection and enumeration of rare carcinoma cells (lte] 1 MM per 10e8 mononuclear cells). Initial results from 21 consecutive cases analyzed using the cMM assay detected marrow MM in 10/21 (48%) of specimens. MM in matched blood samples were frequently detected but generally at lower levels. Quantitative RT-PCR has been performed on 165 patient marrow samples, including all 21 analyzed by the ICC-based assay. RT-PCR assays detected MM in 10-20% of patients depending upon target gene. Results did not correlate closely with each other or with the ICC-based assay. Updated results will be presented, along with correlations with clinicopathologic parameters including tumor size, grade, nodal status, and primary tumor ER/PR/HER2 results.Conclusions: This prospective study compares recently developed and highly sensitive molecular and cell-based methods for MM analysis. Understanding performance differences of new methods should enhance both our understanding of the biology of MM and facilitate the assessment of MM assay(s)in clinical settings.

Authors
Park, JW; Scott, JH; Hwang, ES; Esserman, LJ; Bauer, KD; Bossy, B
MLA Citation
Park, J. W., et al. “Analysis of bone marrow micrometastasis in primary breast cancer: Automated cellular imaging analysis in relation to quantitative RT-PCR and tumor clinicopathologic features.” Breast Cancer Research and Treatment, vol. 69, no. 3, Jan. 2001.
Source
scopus
Published In
Breast Cancer Research and Treatment
Volume
69
Issue
3
Publish Date
2001
Start Page
259

Genomic alterations in tubular breast carcinomas

Tubular carcinoma of the breast is a well-differentiated variant of invasive ductal carcinoma and has been shown to have an exceptionally favorable prognosis, as manifested by a low incidence of lymph node metastases and an excellent overall survival. It is unknown whether this subtype represents an early step along the continuum of development to a more aggressive, poorly differentiated ductal cancer, or whether these cancers are destined to remain well differentiated with limited metastatic potential. We undertook an analysis of 18 pure tubular carcinomas of the breast using comparative genomic hybridization to evaluate the chromosomal changes in these tumors. An average of 3.6 chromosomal alterations of the genome were identified per case. The most frequent change involved loss of 16q (in 78% of tumors) and gain of 1q (in 50% of tumors). All but one case with 1q gain also exhibited a concomitant 16q loss. Other frequent changes involved 16p gain in 7 of 18 cases (39%) and distal 8p loss in 5 of 18 cases (28%). Comparison with known genomic alterations in a mixed group of invasive cancers shows tubular cancer to have fewer overall chromosomal changes per tumor (P < .01), higher frequency of 16q loss (P < .001), and lower frequency of 17p loss (P = .007). These results strongly suggest that tubular carcinomas are a genetically distinct group of breast cancers. © 2001 by W.B. Saunders Company.

Authors
Waldman, FM; Hwang, ES; Etzell, J; Eng, C; DeVries, S; Bennington, J; Thor, A
MLA Citation
Waldman, F. M., et al. “Genomic alterations in tubular breast carcinomas.” Human Pathology, vol. 32, no. 2, Jan. 2001, pp. 222–26. Scopus, doi:10.1053/hupa.2001.21564.
Source
scopus
Published In
Human Pathology
Volume
32
Issue
2
Publish Date
2001
Start Page
222
End Page
226
DOI
10.1053/hupa.2001.21564

Reply

Authors
Purves, D; Lotto, B; Polger, T
MLA Citation
Purves, D., et al. “Reply.” J Cogn Neurosci, vol. 12, no. 5, Sept. 2000.
PMID
11054932
Source
pubmed
Published In
J Cogn Neurosci
Volume
12
Issue
5
Publish Date
2000
Start Page
911

Current national health insurance coverage policies for breast and ovarian cancer prophylactic surgery.

BACKGROUND: The efficacy of prophylactic mastectomy and oophorectomy in reducing breast and ovarian carcinoma has recently been reported in high-risk women. Because cost has become central to medical decision-making, this study was designed to evaluate currently existing coverage policies for these procedures. METHODS: A confidential detailed cross-sectional nationwide survey of 481 medical directors from the American Association of Health Plans, Medicare, and Medicaid was conducted. RESULTS: Of the 150 respondents, 65% (n = 97) had 100,000 or more enrolled members and 35% (n = 53) had fewer than 100,000 enrolled members. Only 44% of private plans have specific policies for coverage of prophylactic mastectomy for a strong family history of breast cancer and 38% of plans for a BRCA mutation. Only 20% of total responding plans had a policy for coverage of prophylactic oophorectomy under any clinical circumstance. Governmental carriers were significantly less likely to have any policy for prophylactic surgery (range, 2%-12%) compared with nongovernmental plans (range, 24%-44%; P < .001). No significant regional differences for coverage policies were identified (P > .05). CONCLUSIONS: Significant variations currently exist for health insurance coverage of prophylactic mastectomy and oophorectomy. As genetic testing becomes widespread, more uniform policies should be established to enable appropriate high-risk candidates equal access and coverage for these procedures.

Authors
Kuerer, HM; Hwang, ES; Anthony, JP; Dudley, RA; Crawford, B; Aubry, WM; Esserman, LJ
MLA Citation
Kuerer, H. M., et al. “Current national health insurance coverage policies for breast and ovarian cancer prophylactic surgery..” Ann Surg Oncol, vol. 7, no. 5, June 2000, pp. 325–32.
PMID
10864338
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
7
Issue
5
Publish Date
2000
Start Page
325
End Page
332

Management of ductal carcinoma in situ.

The dramatic increase in the incidence of ductal carcinoma in situ (DCIS) of the breast has made it imperative for all clinicians to develop a better understanding of this disease. Although this preinvasive form of breast cancer is not life-threatening, treatment options may include mastectomy, breast-conserving surgery, radiotherapy, or tamoxifen. Current treatment modalities may be overly aggressive because many cases of DCIS may not recur or progress to invasive cancer. Until we are better able to identify those patients at low risk for progression, it is unlikely that current treatment will change. The adequate understanding of risk assessment is fundamental to the treatment planning for DCIS, and physicians are encouraged to include patients in the decision-making process.

Authors
Hwang, ES; Esserman, LJ
MLA Citation
Hwang, E. S., and L. J. Esserman. “Management of ductal carcinoma in situ..” Surg Clin North Am, vol. 79, no. 5, Oct. 1999, pp. 1007–viii. Pubmed, doi:10.1016/s0039-6109(05)70058-x.
PMID
10572548
Source
pubmed
Published In
The Surgical Clinics of North America
Volume
79
Issue
5
Publish Date
1999
Start Page
1007
End Page
viii
DOI
10.1016/s0039-6109(05)70058-x

Prophylactic mastectomy in women with a high risk of breast cancer.

Authors
Hamm, RM; Lawler, F; Scheid, D
MLA Citation
Hamm, R. M., et al. “Prophylactic mastectomy in women with a high risk of breast cancer..” N Engl J Med, vol. 340, no. 23, 10 June 1999, pp. 1837–38.
PMID
10366319
Source
pubmed
Published In
The New England Journal of Medicine
Volume
340
Issue
23
Publish Date
1999
Start Page
1837
End Page
1838

Volume of resection in patients treated with breast conservation for ductal carcinoma in situ.

BACKGROUND: The optimal treatment of ductal carcinoma in situ (DCIS) is one of the most controversial issues in the management of breast cancer. Identification of factors that affect the risk of local recurrence is very important as the incidence of DCIS increases and the use of breast conservation becomes more widespread. Because the extent of resection may affect the relapse rate, we hypothesized that larger volumes of resection (VR) may account for the lower local recurrence rates we have previously found in elderly patients. METHODS: Between 1978 and 1990, 173 cases of histologically confirmed DCIS were treated at MSKCC with breast conservation therapy. Of these, complete VR data were available for 126 cases. The VRs thus obtained were divided into two groups, <60 cm3 and > or =60 cm3, and were evaluated for correlating factors. The patients were divided into three groups by age at diagnosis: younger than 40 years, 40 to 69 years, and 70 years or older. RESULTS: The eldest group had a significantly greater proportion of large VRs (30%) as compared to the middle group (11%) and the youngest group (9%) (P=.03, chi2). Although not statistically significant, the large VR group had a lower 6-year actuarial local recurrence rate (5.6%) than did the small VR group (21.3%) (P=.16, log-rank test). This trend was observed even though adjuvant radiotherapy was used less often in patients who had large VRs. CONCLUSION: Breast conservation surgery for DCIS in elderly patients is more likely to employ a large VR. This may explain, at least in part, the observation that elderly patients have a lower local recurrence rate.

Authors
Hwang, ES; Samli, B; Tran, KN; Rosen, PP; Borgen, PI; Van Zee, KJ
MLA Citation
Hwang, E. S., et al. “Volume of resection in patients treated with breast conservation for ductal carcinoma in situ..” Ann Surg Oncol, vol. 5, no. 8, Dec. 1998, pp. 757–63.
PMID
9869524
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
5
Issue
8
Publish Date
1998
Start Page
757
End Page
763

Does the proven benefit of mammography extend to breast cancer patients over age 70?

BACKGROUND: Prospective randomized studies show reduced breast cancer mortality among women offered mammographic screening; yet, few women 70 or older were represented in these trials. We examine the impact of mammography on stage at diagnosis of breast cancer, over the years when mammography came into general use, comparing women aged 40 to 69 with those aged 70 and older. METHODS: We reviewed the records of 1,001 consecutive patients 40 and older treated for invasive or in situ breast cancer in the surgical practice of one of us (H.S.C.) between 1979 and 1993, comparing trends in mammography use, means of diagnosis, tumor size, axillary node status, and pathology. RESULTS: The proportion of cases diagnosed by mammography increased over time to a comparable degree in both age groups, as did the proportion of T1 and DCIS or microinvasive cancers. This trend toward earlier stage appears entirely due to an increasing use of mammography. CONCLUSION: The potential benefit of regular mammography to healthy women aged 70 and older may equal that observed in their younger counterparts.

Authors
Hwang, ES; Cody, HS
MLA Citation
Hwang, E. S., and H. S. Cody. “Does the proven benefit of mammography extend to breast cancer patients over age 70?.” South Med J, vol. 91, no. 6, June 1998, pp. 522–26.
PMID
9634112
Source
pubmed
Published In
Southern Medical Journal
Volume
91
Issue
6
Publish Date
1998
Start Page
522
End Page
526

Surgical pancreatic complications induced by L-asparaginase.

Pancreatitis has been noted to be a potential complication in 2% to 16% of patients undergoing treatment with L-asparaginase for a variety of pediatric neoplasms, but rarely has surgical intervention been necessary. The authors present two fulminant cases of L-asparaginase-induced pancreatitis and review the current literature. The first patient is a 15-year-old boy who underwent induction chemotherapy with L-asparaginase for non-Hodgkin's lymphoma with bone marrow involvement. He presented with diffuse patchy necrosis of the pancreas as well as a large infected pancreatic pseudocyst. He subsequently required operative debridement of the pancreas and external drainage of the pseudocyst. He is currently doing well. The second patient is a 5-year-old boy who was treated with L-asparaginase for a diagnosis of acute lymphocytic leukemia. Within 3 weeks of initiation of therapy, fulminant pancreatitis developed, which progressed to multisystem organ failure. Computed tomography scan demonstrated extensive pancreatic necrosis involving 90% of the gland. He underwent surgical debridement of his necrotic pancreas and wide drainage of the lesser sac. Postoperatively he improved but subsequently multiple complications developed including erosion of his gastroduodenal artery with significant intraabdominal bleeding, which was controlled with angiographic embolization. Subsequently erosion of his endotracheal tube into the innominate vein developed, and he died. L-asparaginase-induced pancreatitis has been described after therapy for various pediatric neoplasms, and the reported cases have usually been self-limiting. However, our cases demonstrate potentially fatal sequelae of this complication and mandate early diagnosis with appropriate surgical intervention in this setting.

Authors
Sadoff, J; Hwang, S; Rosenfeld, D; Ettinger, L; Spigland, N
MLA Citation
Sadoff, J., et al. “Surgical pancreatic complications induced by L-asparaginase..” J Pediatr Surg, vol. 32, no. 6, June 1997, pp. 860–63. Pubmed, doi:10.1016/s0022-3468(97)90636-9.
PMID
9200086
Source
pubmed
Published In
Journal of Pediatric Surgery
Volume
32
Issue
6
Publish Date
1997
Start Page
860
End Page
863
DOI
10.1016/s0022-3468(97)90636-9

Leiomyosarcoma in childhood and adolescence.

BACKGROUND: Few series of leiomyosarcoma in patients < 21 years of age have been reported. We reviewed our institutional experience with this neoplasm to learn disease characteristics, patterns of relapse, and outcome. METHODS: The records of 21 patients with leiomyosarcoma admitted to our institution were reviewed retrospectively; 18 of these were diagnosed after 1970. Overall survival was estimated using the Kaplan-Meier method. RESULTS: Ninety-five percent (20 of 21) were initially treated with a wide local excision that was complete with a negative microscopic margin in 10 (48%). There also was a strong correlation between grade and surgical margins. High-grade tumors were associated with a lower rate of complete resection. The majority underwent additional therapy. Radiation was used to treat both initial and recurrent disease in nine patients, with four of these undergoing brachytherapy. Thirteen patients were treated with adjuvant chemotherapy, most commonly doxorubicin (seven patients) and cisplatin (six patients). The median length of survival was 9.3 years, and there were nine disease-related deaths (43%). Of interest was the progressive decrease in survival with time. The 5-year overall survival rate was 79%; the 10-year rate was 49%. Three patients died of progressive disease > 10 years after initial diagnosis. CONCLUSIONS: We conclude that leiomyosarcomas arising in childhood and adolescence are associated with a good initial chance of survival that decreases progressively over time. Known prognostic factors from larger adult series are consistent with the present data, but they are not provable because of the small number of patients. In particular, the grade was correlated with surgical margins.

Authors
Hwang, ES; Gerald, W; Wollner, N; Meyers, P; La Quaglia, MP
MLA Citation
Hwang, E. S., et al. “Leiomyosarcoma in childhood and adolescence..” Ann Surg Oncol, vol. 4, no. 3, Apr. 1997, pp. 223–27.
PMID
9142383
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
4
Issue
3
Publish Date
1997
Start Page
223
End Page
227

Distribution of the SGLT1 Na+/glucose cotransporter and mRNA along the crypt-villus axis of rabbit small intestine.

The expression of the Na+/glucose cotransporter (SGLT1) mRNA and protein along the crypt-villus axis of the rabbit small intestine was examined using in situ hybridization and immunocytochemical techniques. We detected mRNA in the cells on the villus, but not in the crypts, and the mRNA abundance increased 6-fold from the base to the tip of the villus. SGLT1 protein was restricted to the brush borders of mature enterocytes. We suggest that the high rate of sugar transport across the tips of the villus is due to the transcription of the SGLT1 gene in mature enterocytes, the subsequent translation of SGLT mRNA, and the insertion direct of the functional SGLT1 transporter into the brush border membrane of these cells lining the villus tip.

Authors
Hwang, ES; Hirayama, BA; Wright, EM
MLA Citation
Hwang, E. S., et al. “Distribution of the SGLT1 Na+/glucose cotransporter and mRNA along the crypt-villus axis of rabbit small intestine..” Biochem Biophys Res Commun, vol. 181, no. 3, Dec. 1991, pp. 1208–17. Pubmed, doi:10.1016/0006-291x(91)92067-t.
PMID
1764071
Source
pubmed
Published In
Biochemical and Biophysical Research Communications
Volume
181
Issue
3
Publish Date
1991
Start Page
1208
End Page
1217
DOI
10.1016/0006-291x(91)92067-t

Characterization of a Na+/glucose cotransporter cloned from rabbit small intestine.

The Na+/glucose cotransporter from rabbit intestinal brush border membranes has been cloned, sequenced, and expressed in Xenopus oocytes. Injection of cloned RNA into oocytes increased Na+/sugar cotransport by three orders of magnitude. In this study, we have compared and contrasted the transport properties of this cloned protein expressed in Xenopus oocytes with the native transporter present in rabbit intestinal brush borders. Initial rates of 14C-alpha-methyl-D-glucopyranoside uptake into brush border membrane vesicles and Xenopus oocytes were measured as a function of the external sodium, sugar, and phlorizin concentrations. Sugar uptake into oocytes and brush borders was Na+-dependent (Hill coefficient 1.5 and 1.7), phlorizin inhibitable (Ki 6 and 9 microM), and saturable (alpha-methyl-D-glucopyranoside Km 110 and 570 microM). The sugar specificity was examined by competition experiments, and in both cases the selectivity was D-glucose greater than alpha-methyl-D-glucopyranoside greater than D-galactose greater than 3-O-methyl-D-glucoside. In view of the close similarity between the properties of the cloned protein expressed in oocytes and the native brush border transporter, we conclude that we have cloned the classical Na+/glucose cotransporter.

Authors
Ikeda, TS; Hwang, ES; Coady, MJ; Hirayama, BA; Hediger, MA; Wright, EM
MLA Citation
Ikeda, T. S., et al. “Characterization of a Na+/glucose cotransporter cloned from rabbit small intestine..” J Membr Biol, vol. 110, no. 1, Aug. 1989, pp. 87–95.
PMID
2795642
Source
pubmed
Published In
The Journal of Membrane Biology
Volume
110
Issue
1
Publish Date
1989
Start Page
87
End Page
95
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