Paul Marcom

Overview:

Basic Science:
-Germline and somatic genetic changes in breast cancer.

Translational:
-Identification and management of individuals and families with hereditary cancer risk.
-Communication of cancer risk information to individuals and families.
-Breast cancer prevention.
-Optimizing management of early breast cancer.
-Treatment of metastatic breast cancer


Clinically, Dr. Marcom works as a medical oncologist in the multidisciplinary breast cancer clinic. He participates in clinical trials investigating new chemotherapeutic and biologic treatments. 

Positions:

Adjunct Professor in the Department of Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1989

Baylor University

Medical Resident, Medicine

Duke University

Fellow in Hematology-Oncology, Medicine

Duke University

Grants:

Targeting nuclear FGF receptor to improve chemotherapy response in triple-negative breast cancer

Administered By
Pathology
Awarded By
Department of Defense
Role
Investigator
Start Date
End Date

Markers of short term breast cancer risk in FNA

Administered By
Medicine, Medical Oncology
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Phase II trial of Cetuximab & Carboplatin in Basal-like Breast Cancer

Administered By
Surgery
Awarded By
National Institutes of Health
Role
Co-Principal Investigator
Start Date
End Date

Phase II Trial of Estradiol Therapy for Advanced Breast Cancer

Administered By
Duke Cancer Institute
Awarded By
National Institutes of Health
Role
Co-Principal Investigator
Start Date
End Date

TBCRC 041 Randomized Phase II Trial to Evaluate Alisertib Alone or Combined with Fulvestrant in Women with Advanced, Hormone-Receptor Positive (HR+) Breast Cancer

Administered By
Duke Cancer Institute
Awarded By
Mayo Clinic
Role
Principal Investigator
Start Date
End Date

Publications:

Analysis of Sociodemographic, Clinical, and Genomic Factors Associated With Breast Cancer Mortality in the Linked Surveillance, Epidemiology, and End Results and Medicare Database.

Importance: Understanding interactions among health service, sociodemographic, clinical, and genomic factors in breast cancer disparities research has been limited by a disconnect between health services and basic biological approaches. Objective: To describe the first linkage of Surveillance, Epidemiology, and End Results (SEER)-Medicare data to physical tumor samples and to investigate the interaction among screening detection, socioeconomic status, tumor stage, tumor biology, and breast cancer outcomes within a single context. Design, Setting, and Participants: This population-based cohort study used tumor specimen blocks from a subset of women aged 66 to 75 years with newly diagnosed nonmetastatic, estrogen receptor-positive invasive breast cancer from January 1, 1993, to December 31, 2007. Specimens were obtained from the Iowa and Hawaii SEER Residual Tissue Repositories (RTRs) and linked with Medicare claims data and survival assessed through December 31, 2015. Data were analyzed from August 1, 2018, to July 25, 2021. Exposures: Screening- vs symptom-based detection of tumors was assessed using validated claims-based algorithms. Demographic factors and zip code-based educational attainment and poverty socioeconomic characteristics were obtained via SEER. Main Outcomes and Measures: Molecular subtyping and exploratory genomic analyses were completed using the NanoString Breast Cancer 360 gene expression panel containing the 50-gene signature classifier. Factors associated with overall and breast cancer-specific (BCS) survival were analyzed using Cox proportional hazards regression models combining sociodemographic, clinical, and genomic data. Results: SEER-Medicare data were available for 3522 women (mean [SD] age, 70.9 [2.6] years; 3049 [86.6%] White), of whom 1555 (44.2%) were diagnosed by screening mammogram. In the SEER-Medicare cohort, factors associated with increased BCS mortality included symptomatic detection (hazard ratio [HR], 1.49 [95% CI, 1.16-1.91]), advanced disease stage (HR for stage III, 2.33 [95% CI, 1.41-3.85]), and high-grade disease (HR, 1.85 [95% CI, 1.46-2.34]). The molecular cohort of 130 cases with luminal A/B cancer further revealed increased all-cause mortality associated with genomic upregulation of transforming growth factor β activation and p53 dysregulation (eg, p53 dysregulation: HR, 2.15 [95% CI, 1.20-3.86]) and decreased mortality associated with androgen receptor, macrophage, cytotoxicity, and Treg signaling (eg, androgen receptor signaling: HR, 0.23 [95% CI, 0.12-0.45]). Symptomatic detection (HR, 2.49 [95% CI, 1.19-5.20]) and zip codes with low levels of educational attainment (HR, 5.17 [95% CI, 2.12-12.60]) remained associated with mortality after adjusting for all clinical and demographic factors. Conclusions and Relevance: Linkage of SEER-Medicare data to physical tumor specimens may elucidate associations among biology, health care access, and disparities in breast cancer outcomes. The findings of this study suggest that screening detection and socioeconomic status are associated with survival in patients with locally advanced, estrogen receptor-positive tumors, even after incorporating clinical and genomic factors.
Authors
Robinson, TJ; Wilson, LE; Marcom, PK; Troester, M; Lynch, CF; Hernandez, BY; Parrilla, E; Brauer, HA; Dinan, MA
MLA Citation
Robinson, Timothy J., et al. “Analysis of Sociodemographic, Clinical, and Genomic Factors Associated With Breast Cancer Mortality in the Linked Surveillance, Epidemiology, and End Results and Medicare Database.Jama Netw Open, vol. 4, no. 10, Oct. 2021, p. e2131020. Pubmed, doi:10.1001/jamanetworkopen.2021.31020.
URI
https://scholars.duke.edu/individual/pub1500788
PMID
34714340
Source
pubmed
Published In
Jama Network Open
Volume
4
Published Date
Start Page
e2131020
DOI
10.1001/jamanetworkopen.2021.31020

Circulating tumor cell number and endocrine therapy index in ER positive metastatic breast cancer patients.

Circulating tumor cells (CTC) are prognostic in metastatic breast cancer (MBC). The CTC-endocrine therapy index (CTC-ETI), consisting of CTC-ER (estrogen receptor), BCL2, human epidermal growth factor receptor (HER2), and Ki67 expression, might predict resistance to endocrine therapy (ET) in patients with ER-positive MBC. One hundred twenty-one patients with ER-positive/HER2-negative MBC initiating a new ET after ≥1 lines of ET were enrolled in a prospective, multi-institutional clinical trial. CTC-ETI and clinical/imaging follow-up were performed at baseline and serial time points. Progression-free survival (PFS) and rapid progression (RP; determined at the 3-month time point) were primary endpoints. Associations with clinical outcomes used logrank and Fisher's exact tests. At baseline, 36% (38/107) of patients had ≥5 CTC/7.5 ml whole blood (WB). Patients with ≥5 vs. <5 CTC/7.5 ml WB had significantly worse PFS (median 3.3 vs. 5.9 months, P = 0.03). Elevated CTC at 1 month was associated with even worse PFS (1.9 vs. 5.0 months from the 1-month sample, P < 0.001). Low, intermediate, and high CTC-ETI were observed in 71 (66%), 8 (8%), and 28 (26%) patients, with median PFS of 6.9, 8.5, and 2.8 months, respectively (P = 0.008). Patients with high vs. low CTC and CTC-ETI more frequently experienced RP (CTC: 66% vs. 41%; P = 0.03; CTC-ETI: 79% vs. 40%; P = 0.002). In conclusion, CTC enumeration and the CTC-ETI assay are prognostic at baseline and follow-up in patients with ER-positive/HER2-negative MBC starting new ET. CTC at first follow-up might identify a group of patients with ER-positive MBC that could forego ET, but CTC-ETI did not contribute further.
Authors
Paoletti, C; Regan, MM; Niman, SM; Dolce, EM; Darga, EP; Liu, MC; Marcom, PK; Hart, LL; Smith, JW; Tedesco, KL; Amir, E; Krop, IE; DeMichele, AM; Goodwin, PJ; Block, M; Aung, K; Brown, ME; McCormack, RT; Hayes, DF
MLA Citation
Paoletti, Costanza, et al. “Circulating tumor cell number and endocrine therapy index in ER positive metastatic breast cancer patients.Npj Breast Cancer, vol. 7, no. 1, June 2021, p. 77. Pubmed, doi:10.1038/s41523-021-00281-1.
URI
https://scholars.duke.edu/individual/pub1485925
PMID
34117261
Source
pubmed
Published In
Npj Breast Cancer
Volume
7
Published Date
Start Page
77
DOI
10.1038/s41523-021-00281-1

Patient-reported causes of distress predict disparities in time to evaluation and time to treatment after breast cancer diagnosis.

BACKGROUND: We examined whether the National Comprehensive Cancer Network distress thermometer (DT), a patient-reported outcome measure, could be used to identify levels and causes of distress associated with racial/ethnic disparities in time to care among patients with breast cancer. METHODS: We identified women aged ≥18 years with stage 0-IV breast cancer who were diagnosed in a single health system between January 2014 and July 2016. The baseline visit was defined as the first postdiagnosis, pretreatment clinical evaluation. Zero-inflated negative binomial (ZINB) regression (modeling non-zero DT scores and DT scores = 0) and logistic regression (modeling DT score ≥ 4, threshold for social services referral) were used to examine associations between baseline score (0 = none to 10 = extreme) and types of stressors (emotional, familial, practical, physical, spiritual) after adjustment for race/ethnicity and other characteristics. Linear regression with log transformation was used to identify predictors of time to evaluation and time to treatment. RESULTS: A total of 1029 women were included (median baseline DT score = 4). Emotional, physical, and practical stressors were associated with distress in both the ZINB and logistic models (all P < .05). Black patients (n = 258) were more likely to report no distress than Whites (n = 675; ZINB zero model odds ratio, 2.72; 95% CI, 1.68-4.40; P < .001) despite reporting a similar number of stressors (P = .07). Higher DT scores were associated with shorter time to evaluation and time to treatment while being Black and having physical or practical stressors were associated with delays in both (all P < .05). CONCLUSIONS: Patient-reported stressors predicted delays in time to care, but patient-reported levels of distress did not, with Black patients having delayed time to care despite reporting low levels of distress. We describe anticipatory, culturally responsive strategies for using patient-reported outcomes to address observed disparities.
Authors
Fayanju, OM; Ren, Y; Stashko, I; Power, S; Thornton, MJ; Marcom, PK; Hyslop, T; Hwang, ES
MLA Citation
Fayanju, Oluwadamilola M., et al. “Patient-reported causes of distress predict disparities in time to evaluation and time to treatment after breast cancer diagnosis.Cancer, vol. 127, no. 5, Mar. 2021, pp. 757–68. Pubmed, doi:10.1002/cncr.33310.
URI
https://scholars.duke.edu/individual/pub1464167
PMID
33175437
Source
pubmed
Published In
Cancer
Volume
127
Published Date
Start Page
757
End Page
768
DOI
10.1002/cncr.33310

TBCRC 048: Phase II Study of Olaparib for Metastatic Breast Cancer and Mutations in Homologous Recombination-Related Genes.

PURPOSE: Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi), is approved for the treatment of human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) in germline (g)BRCA1/2 mutation carriers. Olaparib Expanded, an investigator-initiated, phase II study, assessed olaparib response in patients with MBC with somatic (s)BRCA1/2 mutations or g/s mutations in homologous recombination (HR)-related genes other than BRCA1/2. METHODS: Eligible patients had MBC with measurable disease and germline mutations in non-BRCA1/2 HR-related genes (cohort 1) or somatic mutations in these genes or BRCA1/2 (cohort 2). Prior PARPi, platinum-refractory disease, or progression on more than two chemotherapy regimens (metastatic setting) was not allowed. Patients received olaparib 300 mg orally twice a day until progression. A single-arm, two-stage design was used. The primary endpoint was objective response rate (ORR); the null hypothesis (≤ 5% ORR) would be rejected within each cohort if there were four or more responses in 27 patients. Secondary endpoints included clinical benefit rate and progression-free survival (PFS). RESULTS: Fifty-four patients enrolled. Seventy-six percent had estrogen receptor-positive HER2-negative disease. Eighty-seven percent had mutations in PALB2, sBRCA1/2, ATM, or CHEK2. In cohort 1, ORR was 33% (90% CI, 19% to 51%) and in cohort 2, 31% (90% CI, 15% to 49%). Confirmed responses were seen only with gPALB2 (ORR, 82%) and sBRCA1/2 (ORR, 50%) mutations. Median PFS was 13.3 months (90% CI, 12 months to not available/computable [NA]) for gPALB2 and 6.3 months (90% CI, 4.4 months to NA) for sBRCA1/2 mutation carriers. No responses were observed with ATM or CHEK2 mutations alone. CONCLUSION: PARP inhibition is an effective treatment for patients with MBC and gPALB2 or sBRCA1/2 mutations, significantly expanding the population of patients with breast cancer likely to benefit from PARPi beyond gBRCA1/2 mutation carriers. These results emphasize the value of molecular characterization for treatment decisions in MBC.
Authors
Tung, NM; Robson, ME; Ventz, S; Santa-Maria, CA; Nanda, R; Marcom, PK; Shah, PD; Ballinger, TJ; Yang, ES; Vinayak, S; Melisko, M; Brufsky, A; DeMeo, M; Jenkins, C; Domchek, S; D'Andrea, A; Lin, NU; Hughes, ME; Carey, LA; Wagle, N; Wulf, GM; Krop, IE; Wolff, AC; Winer, EP; Garber, JE
MLA Citation
Tung, Nadine M., et al. “TBCRC 048: Phase II Study of Olaparib for Metastatic Breast Cancer and Mutations in Homologous Recombination-Related Genes.J Clin Oncol, vol. 38, no. 36, Dec. 2020, pp. 4274–82. Pubmed, doi:10.1200/JCO.20.02151.
URI
https://scholars.duke.edu/individual/pub1464464
PMID
33119476
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
38
Published Date
Start Page
4274
End Page
4282
DOI
10.1200/JCO.20.02151

TBCRC 030: a phase II study of preoperative cisplatin versus paclitaxel in triple-negative breast cancer: evaluating the homologous recombination deficiency (HRD) biomarker.

BACKGROUND: Cisplatin and paclitaxel are active in triple-negative breast cancer (TNBC). Despite different mechanisms of action, effective predictive biomarkers to preferentially inform drug selection have not been identified. The homologous recombination deficiency (HRD) assay (Myriad Genetics, Inc.) detects impaired double-strand DNA break repair and may identify patients with BRCA1/2-proficient tumors that are sensitive to DNA-targeting therapy. The primary objective of TBCRC 030 was to detect an association of HRD with pathologic response [residual cancer burden (RCB)-0/1] to single-agent cisplatin or paclitaxel. PATIENTS AND METHODS: This prospective phase II study enrolled patients with germline BRCA1/2 wild-type/unknown stage I-III TNBC in a 12-week randomized study of preoperative cisplatin or paclitaxel. The HRD assay was carried out on baseline tissue; positive HRD was defined as a score ≥33. Crossover to an alternative chemotherapy was offered if there was inadequate response. RESULTS: One hundred and thirty-nine patients were evaluable for response, including 88 (63.3%) who had surgery at 12 weeks and 51 (36.7%) who crossed over to an alternative provider-selected preoperative chemotherapy regimen due to inadequate clinical response. HRD results were available for 104 tumors (74.8%) and 74 (71.1%) were HRD positive. The RCB-0/1 rate was 26.4% with cisplatin and 22.3% with paclitaxel. No significant association was observed between HRD score and RCB response to either cisplatin [odds ratio (OR) for RCB-0/1 if HRD positive 2.22 (95% CI: 0.39-23.68)] or paclitaxel [OR for RCB-0/1 if HRD positive 0.90 (95% CI: 0.19-4.95)]. There was no evidence of an interaction between HRD and pathologic response to chemotherapy. CONCLUSIONS: In this prospective preoperative trial in TNBC, HRD was not predictive of pathologic response. Tumors were similarly responsive to preoperative paclitaxel or cisplatin chemotherapy.
Authors
Mayer, EL; Abramson, V; Jankowitz, R; Falkson, C; Marcom, PK; Traina, T; Carey, L; Rimawi, M; Specht, J; Miller, K; Stearns, V; Tung, N; Perou, C; Richardson, AL; Componeschi, K; Trippa, L; Tan-Wasielewski, Z; Timms, K; Krop, I; Wolff, AC; Winer, EP
MLA Citation
Mayer, E. L., et al. “TBCRC 030: a phase II study of preoperative cisplatin versus paclitaxel in triple-negative breast cancer: evaluating the homologous recombination deficiency (HRD) biomarker.Ann Oncol, vol. 31, no. 11, Nov. 2020, pp. 1518–25. Pubmed, doi:10.1016/j.annonc.2020.08.2064.
URI
https://scholars.duke.edu/individual/pub1456534
PMID
32798689
Source
pubmed
Published In
Ann Oncol
Volume
31
Published Date
Start Page
1518
End Page
1525
DOI
10.1016/j.annonc.2020.08.2064