Relative contributions of BRCA1 and BRCA2 mutations to "triple- negative" breast cancer in Ashkenazi Women Journal Article
| Authors: | Comen, E.; Davids, M.; Kirchhoff, T.; Hudis, C.; Offit, K.; Robson, M. |
| Article Title: | Relative contributions of BRCA1 and BRCA2 mutations to "triple- negative" breast cancer in Ashkenazi Women |
| Abstract: | 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 ≥50. 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. © 2011 Springer Science+Business Media, LLC. |
| Keywords: | adult; controlled study; gene mutation; phenotype; ovary cancer; prevalence; epidermal growth factor receptor 2; genotype; heterozygote; oncogene; dna; family history; estrogen receptor; progesterone receptor; ethnic group; brca1; brca2; predictive value; triple negative breast cancer; triple-negative breast cancer; ashkenazi; ashkenazi jewish; brca2 gene |
| Journal Title: | Breast Cancer Research and Treatment |
| Volume: | 129 |
| Issue: | 1 |
| ISSN: | 0167-6806 |
| Publisher: | Springer |
| Date Published: | 2011-08-01 |
| Start Page: | 185 |
| End Page: | 190 |
| Language: | English |
| DOI: | 10.1007/s10549-011-1433-2 |
| PROVIDER: | scopus |
| PUBMED: | 21394499 |
| PMCID: | PMC3405734 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 3 October 2011" - "CODEN: BCTRD" - "Source: Scopus" |
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