Prospective evaluation of BRCA mutations in a large triple-negative breast cancer (TNBC) registry: Implications for germline testing.

Abstract

1026 Background: Although current NCCN guidelines recommend genetic testing (GT) for all TNBC patients aged <60 years (regardless of family history) however due to the lack of prospective information on prevalence of mutations in unselected TNBC patients, these guidelines have not been widely adopted by clinicians and insurance carriers (including Medicare). Data on BRCA mutations from unselected TNBC cohorts are lacking. Aims: In a large TNBC registry, to prospectively determine the 1) prevalence of germline BRCA mutations and 2) validity of current NCCN guidelines for GT. Methods: Patients with stage I-III TNBC presenting for treatment at an academic and surrounding community practices were approached for participation in a prospective registry. All patients underwent comprehensive BRACAnalysis (Myriad). Detailed FH was collected. Mutation prevalence in the entire cohort and in subgroups stratified by FH and age were calculated. A significant family history (SFH) was defined as 1st-/2nd-degree relatives with breast cancer aged <50 years or ovarian cancer at any age. Results: 165 patients with stage I-III TNBC have been enrolled from 2011-2013. Median age 54 (range 24-84yrs), 58% postmenopausal, 29% LN +, 33%, 58% and 9% had stage I, II, III disease respectively. 82% Caucasian, 14% AA, 2% Hispanic, 0.6% Ashkenazi Jewish. Deleterious BRCA1/2 mutations were identified in 13.1% patients (20/152, 15 BRCA1, 5 BRCA2; results pending in 13). 27% of patients had a SFH and 64% had any FH. Mutation rates in patients with or without SFH was 32.5% and 6.1%, respectively. When examined by age at diagnosis, the mutation rates were: 16.6% (<60yrs), 21.8% (<50yrs), 10.6% (51-60yrs), and 0% (>60 yrs). If SFH or age <50, were the only criteria used 35% and 30% of mutations would have been missed. All mutations were identified using the NCCN guidelines. Conclusions: This is the first study to prospectively evaluate BRCA mutations in an unselected TNBC cohort. In this large academic and community registry with negligible Ashkenazi representation, the overall BRCA mutation rate was 13%; 16.6% in those <60 years. These results validate GT based on current NCCN guidelines and support its use in routine clinical practice.