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.

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

PASINI, Barbara;
2012-01-01

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.
2012
21(1)
1
134
147
http://cebp.aacrjournals.org/content/early/2011/12/14/1055-9965.EPI-11-0775.abstract
BRCA1; BRCA2; breast cancer; estrogen receptor; triple-negative tumors
Mavaddat N; Barrowdale D; Andrulis IL; Domchek SM; Eccles D; Nevanlinna H; Ramus SJ; Spurdle A; Robson M; Sherman M; Mulligan AM; Couch FJ; Engel C; McGuffog L; Healey S; Sinilnikova OM; Southey MC; Terry MB; Goldgar D; O'Malley F; John EM; Janavicius R; Tihomirova L; Hansen TV; Nielsen FC; Osorio A; Stavropoulou A; Benítez J; Manoukian S; Peissel B; Barile M; Volorio S; Pasini B; Dolcetti R; Putignano AL; Ottini L; Radice P; Hamann U; Rashid MU; Hogervorst FB; Kriege M; van der Luijt RB; for HEBON; Peock S; Frost D; Evans DG; Brewer C; Walker L; Rogers MT; Side LE; Houghton C; for EMBRACE; Weaver J; Godwin AK; Schmutzler RK; Wappenschmidt B; Meindl A; Kast K; Arnold N; Niederacher D; Sutter C; Deissler H; Gadzicki D; Preisler-Adams S; Varon-Mateeva R; Schönbuchner I; Gevensleben H; Stoppa-Lyonnet D; Belotti M; Barjhoux L; for GEMO Study Collaborators; Isaacs C; Peshkin BN; Caldes T; de Al Hoya M; Cañadas C; Heikkinen T; Heikkilä P; Aittomäki K; Blanco I; Lazaro C; Brunet J; Agnarsson BA; Arason A; Barkardottir RB; Dumont M; Simard J; Montagna M; Agata S; D'Andrea E; Yan M; Fox S; for kConFab Investigators; Rebbeck TR; Rubinstein W; Tung N; Garber JE; Wang X; Fredericksen Z; Pankratz VS; Lindor NM; Szabo C; Offit K; Sakr R; Gaudet MM; Singer CF; Tea MK; Rappaport C; Mai PL; Greene MH; Sokolenko A; Imyanitov E; Toland AE; Senter L; Sweet K; Thomassen M; Gerdes AM; Kruse T; Caligo M; Aretini P; Rantala J; von Wachenfeld A; Henriksson K; for SWE-BRCA Collaborators; Steele L; Neuhausen SL; Nussbaum R; Beattie M; Odunsi K; Sucheston L; Gayther SA; Nathanson K; Gross J; Walsh C; Karlan B; Chenevix-Trench G; Easton DF; Antoniou AC; for the Consortium of Investigators of Modifiers of BRCA1/2
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