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:

Professor 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

Kastan Gray Foundation Project

Administered By
Duke Cancer Institute
Awarded By
Gray Foundation
Role
Researcher
Start Date
End Date

Randomized Trial of Optimal Type of Aerobic Training in Breast Cancer

Administered By
Radiation Oncology
Awarded By
National Institutes of Health
Role
Co 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

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

Publications:

TBCRC 030: A randomized phase II study of preoperative cisplatin versus paclitaxel in TNBC—Evaluating the homologous recombination deficiency (HRD) biomarker.

<jats:p> 507 </jats:p><jats:p> Background: Cisplatin (C) and paclitaxel (T) have activity in TNBC, however predictive biomarkers are lacking. The HRD assay detects impaired dsDNA break repair and may identify BRCA1/2-proficient tumors for treatment with DNA targeting therapies. TBCRC 030 was designed to determine the association between HRD and response to preoperative chemotherapy (CT) in TNBC. Methods: This phase II study randomized patients (pts) with BRCA1/2-proficient/unknown stage I-III TNBC to 12 weeks (wks) of preoperative C or T, followed by surgery. HRD was performed on baseline tissue, with positive scores &gt; 33. Non-responders at 12 wks could crossover to alternative CT. The co-primary objectives were to detect a positive association of HRD with pathologic response (RCB 0-1) vs not (RCB 2-3) to C and a negative association to T. Target accrual of 160 pts was planned to yield 140 evaluable specimens for HRD, providing 90% power for the primary objectives. Analyses used logistic models and likelihood ratio tests with one-sided Type I errors of alpha = 0.05. Results: 140 pts initiated treatment, (72 Arm C, 68 Arm T; 81% T1-2, 62% node negative); 138 were evaluable for response at 12 wks. Post-enrollment testing showed 8 pts (5.8%) with germline DNA-repair pathway mutations. HRD results were available for 95 pts (68.8%, 23 inadequate tissue, 22 pending); 68 (71.6%) were HRD positive: 38 in Arm C, 30 in Arm T. In response-evaluable pts, 87 (63.0%) had surgery at 12 wks, and 51 (37.0%) crossed over. Response outcomes are shown in the Table. No association was seen between HRD score and RCB response to either neoadjuvant C (OR 2.78, [CI 0.61, 17.74]) or T (OR 0.98, CI [0.20, 5.06]). There was no evidence of an interaction between HRD and CT arms. Similarly, no association was observed between HRD score and pCR to either C (OR 1.47, CI [0.40, 5.59]) or T (OR 0.61, CI [0.14, 2.52]). There were no new safety signals. Conclusions: In this mostly BRCA1/2 proficient TNBC cohort, 12 wks of preoperative C or T led to a similar response rate of about 40%; baseline HRD was not predictive of response to preoperative CT, defined either by RCB 0-1 or pCR. Further data will be presented. Correlative analyses of research tissues for markers predictive of response to specific CT in TNBC is ongoing. Clinical trial information: NCT01982448. [Table: see text] </jats:p>
Authors
Mayer, EL; Abramson, VG; Jankowitz, RC; Falkson, CI; Marcom, PK; Traina, TA; Carey, LA; Rimawi, MF; Specht, JM; Miller, K; Stearns, V; Perou, CM; Richardson, AL; Tung, NM; Barry, WT; Tan-Wasielewski, Z; Timms, K; Hartman, A-R; Wolff, AC; Winer, EP
MLA Citation
Mayer, Erica L., et al. “TBCRC 030: A randomized phase II study of preoperative cisplatin versus paclitaxel in TNBC—Evaluating the homologous recombination deficiency (HRD) biomarker.Journal of Clinical Oncology, vol. 37, no. 15_suppl, American Society of Clinical Oncology (ASCO), 2019, pp. 507–507. Crossref, doi:10.1200/jco.2019.37.15_suppl.507.
URI
https://scholars.duke.edu/individual/pub1415114
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
37
Published Date
Start Page
507
End Page
507
DOI
10.1200/jco.2019.37.15_suppl.507

Quantitative assessment of distant recurrence risk in early stage breast cancer using a nonlinear combination of pathological, clinical and imaging variables.

Use of genomic assays to determine distant recurrence risk in patients with early stage breast cancer has expanded and is now included in the American Joint Committee on Cancer staging manual. Algorithmic alternatives using standard clinical and pathology information may provide equivalent benefit in settings where genomic tests, such as OncotypeDx, are unavailable. We developed an artificial neural network (ANN) model to nonlinearly estimate risk of distant cancer recurrence. In addition to clinical and pathological variables, we enhanced our model using intraoperatively determined global mammographic breast density (MBD) and local breast density (LBD). LBD was measured with optical spectral imaging capable of sensing regional concentrations of tissue constituents. A cohort of 56 ER+ patients with an OncotypeDx score was evaluated. We demonstrated that combining MBD/LBD measurements with clinical and pathological variables improves distant recurrence risk prediction accuracy, with high correlation (r = 0.98) to the OncotypeDx recurrence score.
Authors
Nichols, BS; Chelales, E; Wang, R; Schulman, A; Gallagher, J; Greenup, RA; Geradts, J; Harter, J; Marcom, PK; Wilke, LG; Ramanujam, N
MLA Citation
Nichols, Brandon S., et al. “Quantitative assessment of distant recurrence risk in early stage breast cancer using a nonlinear combination of pathological, clinical and imaging variables.J Biophotonics, June 2020, p. e201960235. Pubmed, doi:10.1002/jbio.201960235.
URI
https://scholars.duke.edu/individual/pub1447971
PMID
32573935
Source
pubmed
Published In
J Biophotonics
Published Date
Start Page
e201960235
DOI
10.1002/jbio.201960235

Breast Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology.

Several new systemic therapy options have become available for patients with metastatic breast cancer, which have led to improvements in survival. In addition to patient and clinical factors, the treatment selection primarily depends on the tumor biology (hormone-receptor status and HER2-status). The NCCN Guidelines specific to the workup and treatment of patients with recurrent/stage IV breast cancer are discussed in this article.
Authors
Gradishar, WJ; Anderson, BO; Abraham, J; Aft, R; Agnese, D; Allison, KH; Blair, SL; Burstein, HJ; Dang, C; Elias, AD; Giordano, SH; Goetz, MP; Goldstein, LJ; Isakoff, SJ; Krishnamurthy, J; Lyons, J; Marcom, PK; Matro, J; Mayer, IA; Moran, MS; Mortimer, J; O'Regan, RM; Patel, SA; Pierce, LJ; Rugo, HS; Sitapati, A; Smith, KL; Smith, ML; Soliman, H; Stringer-Reasor, EM; Telli, ML; Ward, JH; Young, JS; Burns, JL; Kumar, R
MLA Citation
Gradishar, William J., et al. “Breast Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology.Journal of the National Comprehensive Cancer Network : Jnccn, vol. 18, no. 4, Apr. 2020, pp. 452–78. Epmc, doi:10.6004/jnccn.2020.0016.
URI
https://scholars.duke.edu/individual/pub1437155
PMID
32259783
Source
epmc
Published In
Jnccn Journal of the National Comprehensive Cancer Network
Volume
18
Published Date
Start Page
452
End Page
478
DOI
10.6004/jnccn.2020.0016

The immune profile of small HER2-positive breast cancers: a secondary analysis from the APT trial.

BACKGROUND: Previous data suggest that the immune microenvironment plays a critical role in human epidermal growth factor receptor 2 (HER2) -positive breast cancer; however, there is little known about the immune profiles of small HER2-positive tumors. In this study, we aimed to characterize the immune microenvironment of small HER2-positive breast cancers included in the Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer (APT) trial and to correlate the immune markers with pathological and molecular tumor characteristics. PATIENTS AND METHODS: The APT trial was a multicenter, single-arm, phase II study of paclitaxel and trastuzumab in patients with node-negative HER2-positive breast cancer. The study included 406 patients with HER2-positive, node-negative breast cancer, measuring up to 3cm. Exploratory analysis of tumor infiltrating lymphocytes (TIL), programmed death-ligand 1 (PD-L1) expression (by immunohistochemistry), and immune gene signatures using data generated by nCounter PanCancer Pathways Panel (NanoString Technologies, Seattle, WA), and their association with pathological and molecular characteristics was carried out. RESULTS: Of the 406 patients, 328 (81%) had at least one immune assay carried out: 284 cases were evaluated for TIL, 266 for PD-L1, and 213 for immune gene signatures. High TIL (≥60%) were seen with greater frequency in hormone-receptor (HR) negative, histological grades 2 and 3, as well in HER2-enriched and basal-like tumors. Lower stromal PD-L1 (≤1%) expression was seen with greater frequency in HR-positive, histological grade 1, and in luminal tumors. Both TIL and stromal PD-L1 were positively correlated with 10 immune cell signatures, including Th1 and B cell signatures. Luminal B tumors were negatively correlated with those signatures. Significant correlation was seen among these immune markers; however, the magnitude of correlation did not indicate a monotonic relationship between them. CONCLUSION: Immune profiles of small HER2-positive breast cancers differ according to HR status, histological grade, and molecular subtype. Further work is needed to explore the implication of these findings on disease outcome. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00542451.
Authors
Barroso-Sousa, R; Barry, WT; Guo, H; Dillon, D; Tan, YB; Fuhrman, K; Osmani, W; Getz, A; Baltay, M; Dang, C; Yardley, D; Moy, B; Marcom, PK; Mittendorf, EA; Krop, IE; Winer, EP; Tolaney, SM
MLA Citation
Barroso-Sousa, R., et al. “The immune profile of small HER2-positive breast cancers: a secondary analysis from the APT trial.Ann Oncol, vol. 30, no. 4, Apr. 2019, pp. 575–81. Pubmed, doi:10.1093/annonc/mdz047.
URI
https://scholars.duke.edu/individual/pub1428898
PMID
31987274
Source
pubmed
Published In
Ann Oncol
Volume
30
Published Date
Start Page
575
End Page
581
DOI
10.1093/annonc/mdz047

TBCRC 031: Randomized Phase II Study of Neoadjuvant Cisplatin Versus Doxorubicin-Cyclophosphamide in Germline BRCA Carriers With HER2-Negative Breast Cancer (the INFORM trial).

PURPOSE: Platinum compounds have activity in triple-negative breast cancer (TNBC) in germline BRCA mutation carriers (BRCA carriers). Limited data exist for estrogen receptor (ER)-positive (+) breast cancer among BRCA carriers. INFORM is a randomized, multicenter, phase II trial comparing pathologic complete response (pCR) rates (ypT0/is, N0) after neoadjuvant single-agent cisplatin (CDDP) versus doxorubicin-cyclophosphamide (AC) in BRCA carriers with stage I-III human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Secondary objectives included residual cancer burden scores (RCB) of 0 or 1 (combined) and toxicity. The goal was to determine whether pCR was ≥ 20% higher with CDDP than AC. PATIENTS AND METHODS: BRCA carriers with cT1-3 (≥ 1.5 cm), cN0-3 HER2-negative breast cancer were randomly assigned to preoperative CDDP (75 mg/m2 every 3 weeks × 4 doses) or AC (doxorubicin 60 mg/m2; cyclophosphamide 600 mg/m2 every 2-3 weeks × 4 doses) followed by surgery. Pathologic responses were confirmed by central review. RESULTS: A total of 118 patients were randomly assigned; 117 were included in outcome analyses. Mean age was 42 years (range, 24-73 years); 69% were BRCA1+, 30% were BRCA2+, and 2% had both mutations. Clinical stage was I for 19%, II for 63%, and III for 18%; 45% had nodal involvement at baseline. Seventy percent had TNBC. Clinical and tumor characteristics were well matched between treatment arms. The pCR rate was 18% with CDDP and 26% with AC, yielding a risk ratio (RR) of 0.70 (90% CI, 0.39 to 1.2). The risk of RCB 0 or 1 (RCB 0/1) was 33% with CDDP and 46% with AC (RR, 0.73; 90% CI, 0.50 to 1.1). Both regimens were generally well tolerated without unexpected toxicities. CONCLUSION: pCR or RCB 0/1 is not significantly higher with CDDP than with AC in BRCA carriers with stage I-III HER2-negative breast cancer for both TNBC and ER+/HER2-negative disease.
Authors
Tung, N; Arun, B; Hacker, MR; Hofstatter, E; Toppmeyer, DL; Isakoff, SJ; Borges, V; Legare, RD; Isaacs, C; Wolff, AC; Marcom, PK; Mayer, EL; Lange, PB; Goss, AJ; Jenkins, C; Krop, IE; Winer, EP; Schnitt, SJ; Garber, JE
MLA Citation
URI
https://scholars.duke.edu/individual/pub1433326
PMID
32097092
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
38
Published Date
Start Page
1539
End Page
1548
DOI
10.1200/JCO.19.03292