Relative contributions of BRCA1 and BRCA2 mutations to ‘‘triple-negative’’ breast cancer in Ashkenazi Women
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : E. Comen M. Davids T. Kirchhoff C. Hudis K. Offit M. Robson
- چاپ و سال / کشور: 2011
Description
Approximately 10% of Ashkenazi Jewish (AJ) women with breast cancer (BC) carry a founder mutation in BRCA1 or BRCA2. There is an association between BRCA1 mutations and ‘‘triple-negative’’ breast cancer (TNBC) [estrogen receptor (ER) and progesterone receptor (PR) negative, HER2 negative]. We sought to determine the predictive value of the TNBC phenotype for the presence of a BRCA mutation in AJ women ascertained without respect to family history. DNA samples were collected between 8/2000 and 6/2004 from a prevalent cohort of unselected AJ women with breast cancer (median age at diagnosis 56 years). Samples (n = 451) were genotyped for AJ founder mutations. 352 (78.0%) cancers were ER positive, 254 (56.3%) PR positive, and 91 (20.2%) ER negative/PR negative. 63 (14.0%) cancers were HER2 positive (immunohistochemistry 3? or FISH[2.2). TNBC was observed in 64 patients (14.2%). Founder mutations were detected in 48 samples (10.6%) including 25/64 TNBC (39.1%; 19 BRCA1, 6 BRCA2). Among TNBC patients with family history (FH) information, 6/15 (40%) mutations were found in women without breast or ovarian cancer in a close relative. The positive predictive value of TNBC for a BRCA1 mutation was 30% overall, 50% in women diagnosed\50 years, and 14% in women diagnosed C50. TNBC was significantly associated with detecting a mutation in either BRCA1 or BRCA2, but only 25/52 (48%) mutation-associated cancers were TNBC. The prevalence of BRCA founder mutations exceeds 50% in subsets of AJ women with TNBC. FH is an imperfect predictor of mutation status in this group. A significant number of mutation-associated TNBC are due to BRCA2.
Breast Cancer Res Treat (2011) 129:185–190 DOI 10.1007/s10549-011-1433-2 Received: 25 February 2011 / Accepted: 28 February 2011 / Published online: 11 March 2011 Springer Science+Business Media, LLC. 2011
