168P - Triple-negative breast cancer and BRCA mutation: looking at the future

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Breast Cancer
Presenter Zelmira Ballatore
Citation Annals of Oncology (2016) 27 (6): 43-67. 10.1093/annonc/mdw364
Authors Z. Ballatore, M. Pistelli, R. Bracci, F. Bianchi, E. Maccaroni, L. Belvederesi, C. Brugiati, S. Pagliaretta, M. De Lisa, A. Della Mora, L. Cantini, L. Bastianelli, A. Pagliacci, N. Battelli, R. Berardi
  • 1. Clinica Di Oncologia Medica E Centro Regionale Di Genetica Oncologica, AOU Ospedali Riuniti Ancona Università Politecnica delle Marche, 60126 - Ancona/IT

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.

Clinical trial identification

Legal entity responsible for the study

N/A

Funding

Clinica di Oncologia Medica e Centro Regionale di Genetica Oncologica, Università Politecnica delle Marche e AOU Ospedali Riuniti Ancona

Disclosure

All authors have declared no conflicts of interest.