Endocrine therapy is not effective in BRCA2 mutated breast cancers even when they express hormonal receptors

Abstract

Background: BRCA germ-lines mutations increased Breast Cancer (BC) risk and may contribute to different clinical and biological features. However, their impact on prognosis and treatment choice has not completely defined. Aim of our study was to compare breast cancer features in BRCA1 and BRCA2 mutation carriers with that in patients with sporadic disease and to assess their impact on prognosis. Patients and methods: Tumor pathologic features and clinical characteristics were examined in 287 patients (269 female and 18 male) with invasive breast cancer eligible for a genetic testing for BRCA mutations between 1996 and 2013 at our Institution. Subgroups differences were analysed using Chi Square Test. The Cox univariate and multivariate proportional hazard regression model was used to evaluate the prognostic factors on overall survival (OS). Results: Of the 287 assessed breast cancer patients, 90 (31.4%) hosted a BRCA pathogenic mutation: 46.7% were BRCA1 and 53.3% BRCA2 carriers. BRCA1 carriers developed more often triple negative tumors (64.3%) than the other two groups (14.5% and 18.7% in BRCA2 and sporadic tumors, respectively; p < 0.0001). Conversely, BRCA2-tumors showed a higher frequency of luminal phenotype (75%), in comparison with BRCA1-tumors (21.4%) and sporadic tumors (63.9%; p < 0.0001); BRCA2-tumors had a higher incidence of lymphovascular invasion (LVI, 35.4%) than the other two groups (14.3% and 23.4% in BRCA1 and sporadic tumors, respectively; p = 0.02). At multivariate analysis a better OS was correlated to a positive estrogen receptor expression (p = 0.002) and to the absence of BRCA2 mutation (p = 0.03) and lympho-vascular invasion (p = 0.007). Conclusions: Outcomes in carriers of BRCA1 mutations, were similar to outcomes in patients with sporadic disease. Conversely, risk of distant recurrence and death was significantly higher in BRCA2 mutation carriers when compared with those with sporadic disease, although they develop more often luminal BC. Thus, our observations may suggest a more intensive adjuvant approach in this subset of patients, even when they have an high expression of hormone-receptors.