Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA).

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.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. 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. 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 × 10(-5)), but increased with age at diagnosis among BRCA2, carriers (P-trend = 6.8 × 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 × 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 × 10(-14)), and medullary tumors BRCA1-related (OR for BRCA2 = 0.25, 95% CI: 0.18-0.35; P = 2.3 × 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.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-CC