Pathology of Breast and Ovarian Cancers among BRCA1 and BRCA2 Mutation Carriers: Results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA)

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RESEARCH PRODUCT

Pathology of Breast and Ovarian Cancers among BRCA1 and BRCA2 Mutation Carriers: Results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA)

N. Mavaddat D. Barrowdale I.l. Andrulis S.m. Domchek D. Eccles H. Nevanlinna S.j. Ramus A. Spurdle M. Robson M. Sherman A.m. Mulligan F.j. Couch C. Engel L. Mcguffog S. Healey O.m. Sinilnikova M.c. Southey M.b. Terry D. Goldgar F. O'malley E.m. John R. Janavicius L. Tihomirova T.v.o. Hansen F.c. Nielsen A. Osorio A. Stavropoulou J. Benitez S. Manoukian B. Peissel M. Barile S. Volorio B. Pasini R. Dolcetti A.l. Putignano L. Ottini P. Radice U. Hamann M.u. Rashid F.b. Hogervorst M. Kriege R.b. Van Der Luijt S. Peock D. Frost D.g. Evans C. Brewer L. Walker M.t. Rogers L.e. Side C. Houghton J. Weaver A.k. Godwin R.k. Schmutzler B. Wappenschmidt A. Meindl K. Kast N. Arnold D. Niederacher C. Sutter H. Deissler D. Gadzicki S. Preisler-adams R. Varon-mateeva I. Schonbuchner H. Gevensleben D. Stoppa-lyonnet M. Belotti L. Barjhoux C. Isaacs B.n. Peshkin T. Caldes M. De La Hoya C. Canadas T. Heikkinen P. Heikkila K. Aittomaki I. Blanco C. Lazaro J. Brunet B.a. Agnarsson A. Arason R.b. Barkardottir M. Dumont J. Simard M. Montagna S. Agata E. D'andrea M. Yan S. Fox T.r. Rebbeck W. Rubinstein N. Tung J.e. Garber X.s. Wang Z. Fredericksen V.s. Pankratz N.m. Lindor C. Szabo K. Offit R. Sakr M.m. Gaudet C.f. Singer M.k. Tea C. Rappaport P.l. Mai M.h. Greene A. Sokolenko E. Imyanitov A.e. Toland L. Senter K. Sweet M. Thomassen A.m. Gerdes T. Kruse M. Caligo P. Aretini J. Rantala A. Von Wachenfeld K. Henriksson L. Steele S.l. Neuhausen R. Nussbaum M. Beattie K. Odunsi L. Sucheston S.a. Gayther K. Nathanson J. Gross C. Walsh B. Karlan G. Chenevix-trench D.f. Easton A.c. Antoniou Hebon Embrace Gemo Study Collaborators Kconfab Investigators Swe-brca Collaborators Consortium Investigators Modifiers

subject

Oncology Pathology endocrine system diseases Epidemiology Genes BRCA2 Genes BRCA1 Estrogen receptor Gene mutation 0302 clinical medicine Cancer screening Medicine skin and connective tissue diseases Estrogen Receptor Status Ovarian Neoplasms 0303 health sciences Middle Aged female genital diseases and pregnancy complications 3. Good health Serous fluid triple-negative tumors Oncology 030220 oncology & carcinogenesis Female estrogen receptor Adult medicine.medical_specialty BRCA1; BRCA2; breast cancer; estrogen receptor; triple-negative tumors Hereditary cancer and cancer-related syndromes Genetics and epigenetic pathways of disease [ONCOL 1]Breast Neoplasms Article 03 medical and health sciences breast cancer Breast cancer SDG 3 - Good Health and Well-being Translational research [ONCOL 3]Internal medicine Humans Genetic Predisposition to Disease Genetics and epigenetic pathways of disease Translational research [NCMLS 6]Germ-Line Mutation Aged 030304 developmental biology Hereditary cancer and cancer-related syndromes [ONCOL 1]business.industry Cancer BRCA1 medicine.disease BRCA2 Neoplasm Grading business Ovarian cancer

description

Abstract 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 × 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. Cancer Epidemiol Biomarkers Prev; 21(1); 134–47. ©2011 AACR.

year	journal	country	edition	language
2012-01-31

10.1158/1055-9965.epi-11-0775 https://hdl.handle.net/1887/97446