Triple-negative breast cancer and BRCA mutation: looking at the future

Abstract

Background: More than 75% of breast carcinomas that develop in BRCA mutation carriers (BRCA+) are triple-negative breast cancer (TNBC). Despite higher prevalence, it is controversial whether BRCA+ have lower survival. The aim of this study was to compare disease free survival (DFS) and overall survival (OS) in TNBC patients with and without deleterious BRCA1/2 mutations. Methods: A total of 116 women with TNBC referred to our Institution for genetic counseling and underwent BRCA genetic testing between 2002 and 2015, 13 patients with a BRCA variant of uncertain significance (VUS) were excluded. Associations between clinical features and outcomes were evaluated using univariate and multivariate Cox analysis. Results: Overall, 103 women were included, 55 (47%) were BRCA+ (BRCA1 n = 48, BRCA2 n = 7) and 48 cases wild-type (BRCA-). Recurrent mutations were: 2 frameshift mutations in exon 11 in 5 cases with 3901delT and 4 with 962del4 Stop 297 respectively. Six patients presented exon 5 frameshift mutation (300T > G) and 5 women presented large genomic rearrangement (Del 1 and 2). Median age was 42 years in BRCA+ and 48 years in BRCA-. The two patient groups were comparable for prognostic factors. Median follow-up was 6.2 years (range 0.5-22.8), the 5-year RFS rates were 79% and 72% (P = 0.12) in BRCA+ and BRCA- and 5-year OS rates was 83% in both groups. No significant prognostic difference was evidenced in DFS (p = 0.54) and OS (p = 0.24). A better DFS was associated to early stage and absence of lymphovascular invasion; these findings were confirmed to multivariate analysis (p = 0.01, HR 3.02 CI 1.28-7.11 and p = 0.02, HR 3.01 CI 1.23-7.38). The OS was correlated only to early stage (p = 0.04, HR 0.33 CI 0.09-0.96). Conclusions: Given the 47% prevalence of deleterious BRCA1 mutations, referral for genetic testing should be considered in TNBC. The 4 detected deleterious BRCA1 mutations seem recurrent in our Country. TNBC prognosis is similar between BRCA+ and sporadic disease. These findings parallel previous literature data showing limited clinical impact of BRCA status as a whole in TNBC survival. Study limitation include small number of events which may have reduced statistical power. Further studies are required to find prognostic/predictive factors in order to guide therapy in TNBC BRCA positive and negative.