TY - JOUR

T1 - Pathology of Breast and Ovarian Cancers among BRCA1 and BRCA2 Mutation Carriers: Results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA)

AU - Mavaddat, Nasim

AU - Barrowdale, Daniel

AU - Andrulis, Irene L

AU - Domchek, Susan M

AU - Eccles, Diana

AU - Nevanlinna, Heli

AU - Ramus, Susan J

AU - Spurdle, Amanda

AU - Robson, Mark

AU - Sherman, Mark

AU - Mulligan, Anna Marie

AU - Couch, Fergus J

AU - Engel, Christoph

AU - McGuffog, Lesley

AU - Healey, Sue

AU - Sinilnikova, Olga M

AU - Southey, Melissa C

AU - Terry, Mary Beth

AU - Goldgar, David

AU - O'Malley, Frances

AU - John, Esther M

AU - Janavicius, Ramunas

AU - Tihomirova, Laima

AU - Hansen, Thomas V O

AU - Nielsen, Finn C

AU - Osorio, Ana

AU - Stavropoulou, Alexandra

AU - Benítez, Javier

AU - Manoukian, Siranoush

AU - Peissel, Bernard

AU - Barile, Monica

AU - Volorio, Sara

AU - Pasini, Barbara

AU - Dolcetti, Riccardo

AU - Putignano, Anna Laura

AU - Ottini, Laura

AU - Radice, Paolo

AU - Hamann, Ute

AU - Rashid, Muhammad U

AU - Hogervorst, Frans B

AU - Kriege, Mieke

AU - van der Luijt, Rob B

AU - Peock, Susan

AU - Frost, Debra

AU - Evans, D Gareth

AU - Brewer, Carole

AU - Walker, Lisa

AU - Rogers, Mark T

AU - Side, Lucy E

AU - Gerdes, Anne-Marie

AU - for HEBON

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

U2 - 10.1158/1055-9965.EPI-11-0775

DO - 10.1158/1055-9965.EPI-11-0775

M3 - Journal article

C2 - 22144499

VL - 21

SP - 134

EP - 147

JO - Cancer Epidemiology, Biomarkers & Prevention

JF - Cancer Epidemiology, Biomarkers & Prevention

SN - 1055-9965

IS - 1

ER -