Journal
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
Volume 21, Issue 1, Pages 134-147Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1055-9965.EPI-11-0775
Keywords
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Funding
- University of Kansas Cancer Center
- Kansas Bioscience Authority Eminent Scholar Program
- Cancer Research UK [C12292/A11174, C1287/A10118, C1287/A11990, C5047/A8385]
- European Community [223175, HEALTH-F2-2009-223175]
- Medical Research Council
- National Cancer Institute, NIH, [RFA-CA-06-503]
- Breast Cancer Family Registry and Principal Investigators, including Cancer Care Ontario [U01 CA69467]
- Columbia University [U01 CA69398]
- Fox Chase Cancer Center [U01 CA69631]
- Huntsman Cancer Institute [U01 CA69446]
- Cancer Prevention Institute of California [U01 CA69417]
- University of Melbourne [U01 CA69638]
- Research Triangle Institute Informatics Support Center (RFP) [N02PC45022-46]
- Cancer Care Ontario
- U.S. National Cancer Institute, NIH under RFA [CA-06-503]
- Research Council of Lithuania [LIG-19/2010]
- LSC [05.0023.04., 10.0010.08]
- NEYE Foundation
- Fundacion Mutua Madrilena
- Asociacion Espanola Contra el Cancer
- Spanish Ministry of Science and Innovation [FIS PI08 1120]
- Basque Foundation for Health Innovation and Research (BIOEF) [BIO07/CA/006]
- DKFZ
- Dutch Cancer Society [NKI1998-1854, NKI2004-3088, NKI2007-3756]
- ZonMW [91109024]
- NIHR
- Royal Marsden NHS Foundation Trust
- Eileen Stein Jacoby Fund [U01CA69631, 5U01CA113916]
- Centre of Molecular Medicine Cologne (CMMC) [109076]
- Ligue National Contre le Cancer and The Association
- National Cancer Institute [NCI P30 CA51008-12]
- Fisher Center for Familial Cancer Research
- Helsinki University Central Hospital
- Academy of Finland [132473]
- Finnish Cancer Society
- Sigrid Juselius Foundation
- Icelandic Association Walking for Breast Cancer Research
- Landspitali University Hospital
- Canadian Breast Cancer Research [019511]
- Ministero della Salute [RFPS 2006-5-341353, ACC2/R6.9]
- Progetto Tumori Femminili
- National Breast Cancer Foundation
- National Health and Medical Research Council (NHMRC) [145684, 288704, 454508]
- Queensland Cancer Fund
- Cancer Councils of New South Wales, Victoria, Tasmania and South Australia
- Cancer Foundation of Western Australia
- NIH [CA116167, CA128978, CA74415]
- Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]
- Komen Foundation for the Cure
- Breast Cancer Research Foundation
- U.S. National Cancer Institute
- Westat, Inc. [NO2-CP-11019-50, N02-CP-65504]
- Russian Federation for Basic Research [10-04-92601, 11-04-00250, 11-04-00227]
- Federal Agency for Science and Innovations [02.740.11.0780]
- Commission of the European Communities [PITN-GA-2009-238132]
- OSU Comprehensive Cancer Center
- ITT (Tuscany Institute for Tumors) [2010-2012]
- NCI Bay Area Breast Cancer SPORE [P50-CA058207]
- Avon Foundation
- UCSF Helen Diller Family Comprehensive Cancer Center
- CRUK
- Cancer Genetics Network and Marjorie Cohen Foundation
- American Cancer Society [SIOP-06-258-01-CCE]
- DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS [N01CP011019] Funding Source: NIH RePORTER
- NATIONAL CANCER INSTITUTE [ZIACP010126, U01CA069638, R01CA106588, P50CA058207, P30CA051008, U01CA069417, U01CA069467, R01CA122340, U01CA069446, U01CA116167, R01CA128978, R01CA140323, U01CA069631, R01CA116167, U01CA113916, R01CA074415, ZIACP010144, U01CA069398, P50CA116201] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [Z01AI000732] Funding Source: NIH RePORTER
- Cancer Research UK [15007, 11174, 10118, 11022] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0510-10096] Funding Source: researchfish
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Background: Previously, small studies have found that BRCA1 and BRCA2 breast tumors differ in their pathology. Analysis of larger datasets of mutation carriers should allow further tumor characterization. Methods: We used data from 4,325 BRCA1 and 2,568 BRCA2 mutation carriers to analyze the pathology of invasive breast, ovarian, and contralateral breast cancers. Results: There was strong evidence that the proportion of estrogen receptor (ER)-negative breast tumors decreased with age at diagnosis among BRCA1 (P-trend = 1.2 x 10(-5)), but increased with age at diagnosis among BRCA2, carriers (P-trend 6.8 x 10(-6)). The proportion of triple-negative tumors decreased with age at diagnosis in BRCA1 carriers but increased with age at diagnosis of BRCA2 carriers. In both BRCA1 and BRCA2 carriers, ER-negative tumors were of higher histologic grade than ER-positive tumors (grade 3 vs. grade 1; P = 1.2 x 10(-13) for BRCA1 and P = 0.001 for BRCA2). ER and progesterone receptor (PR) expression were independently associated with mutation carrier status [ER-positive odds ratio (OR) for BRCA2 = 9.4, 95% CI: 7.0-12.6 and PR-positive OR = 1.7, 95% CI: 1.3-2.3, under joint analysis]. Lobular tumors were more likely to be BRCA2-related (OR for BRCA2 = 3.3, 95% CI: 2.4-4.4; P = 4.4 x 10(-14)), and medullary tumors BRCA1-related (OR for BRCA2 = 0.25, 95% CI: 0.18-0.35; P = 2.3 x 10(-15)). ER-status of the first breast cancer was predictive of ER-status of asynchronous contralateral breast cancer (P = 0.0004 for BRCA1; P = 0.002 for BRCA2). There were no significant differences in ovarian cancer morphology between BRCA1 and BRCA2 carriers (serous: 67%; mucinous: 1%; endometrioid: 12%; clear-cell: 2%). Conclusions/Impact: Pathologic characteristics of BRCA1 and BRCA2 tumors may be useful for improving risk-prediction algorithms and informing clinical strategies for screening and prophylaxis. Cancer Epidemiol Biomarkers Prev; 21(1); 134-47. (C) 2011 AACR.
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