Prevalence of BRCA1 mutations in triple negative breast cancer (BC)

Abstract

508 Background: 90% of BCs in women with germline BRCA1 mutations are ER, PR and HER2 negative (so-called “Triple Negatives”), and 80–90% of triple negative BCs are “basal-like” by DNA microarray and IHC analysis. Prevalence of germline BRCA1 mutations among women with triple negative BC may therefore, be elevated, and underestimated by available calculation models, which do not take tumor features into account. Methods: We randomly identified 200 women from the Dana-Farber/Harvard Cancer Center SPORE annotated specimen bank with histologically confirmed primary invasive, ER, PR and HER2 negative BC. Myriad prevalence tables for BRCA1 were used to estimate the probability that each subject carried a BRCA1 mutation according to age at BC diagnosis, family and personal history of breast and/or ovarian cancer, and Ashkenazi Jewish ancestry. Full sequencing analysis for BRCA1 germline mutations is in progress. Results: The median age at diagnosis of triple negative BC was 49 years (range 26–79). The majority of tumors were high grade (89%) ductal (95%) carcinomas; median tumor size was 2 cm, 50% had positive nodes. 3 patients had a personal history of ovarian cancer and 13 reported Ashkenazi Jewish ancestry. 44% had at least one first or second degree relative with BC; 12% had at least one relative with ovarian cancer. The estimated probability of detecting a BRCA1 mutation according to the Myriad tables ranged from 0.019 to 0.386 (median 0.039): the total expected number of BRCA1 mutations was 11. In a subgroup of 23 patients (12%), who had undergone clinical testing, 2.7 BRCA1 and 1.4 BRCA2 mutations were expected according to the Myriad tables. However, 9 deleterious BRCA1 mutations (39.1%) were found; 2 patients had a BRCA2 mutation (8.7%). Conclusions: The relative excess of BRCA1 mutations in a small group of patients with triple negative BC suggests that established risk factors alone may underestimate the prevalence of BRCA1 mutations among women with this BC subtype. We anticipate that complete BRCA1 analysis of our entire group will more definitively estimate the prevalence BRCA1 mutations among women with triple negative BC. No significant financial relationships to disclose.