Relative contributions of BRCA1 and BRCA2 mutations to "triple-negative" breast cancer in Ashkenazi Women

Breast Cancer Res Treat. 2011 Aug;129(1):185-90. doi: 10.1007/s10549-011-1433-2. Epub 2011 Mar 11.


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.

MeSH terms

  • Adult
  • Aged
  • BRCA1 Protein / genetics*
  • BRCA2 Protein / genetics*
  • Breast Neoplasms / ethnology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Female
  • Founder Effect
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Jews / genetics
  • Middle Aged
  • Mutation / genetics*
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism


  • BRCA1 Protein
  • BRCA2 Protein
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Receptor, ErbB-2