BRCA1 status, molecular markers, clinical variables in breast cancer patients with high probability of having an inherited genetic mutation

Abstract

9648 Background: to evaluate the clinical features and outcomes of Breast Cancer (BC) patients with genetic susceptibility to this disease and to investigate the contribution of BRCA1 germline mutation to the phenotype of these tumors. Methods: we reviewed clinical and pathological records of 144 women with autosomal dominant inheritance of breast (+/- ovarian) cancer risk. All women underwent full genetic counseling. Of these, 101 selected patients with high probability of having a germ-line mutation were tested for BRCA1 mutation analysis. Exon 11 was screened for BRCA1 mutations using Protein Truncation Test; mutations detected were confirmed by Direct Sequencing. All the other exons were analyzed by DS. Results: the two different risk groups had similar clinical outcomes. Of the 57 patients with completed mutation analysis, 44 (77%) patients had wild type BRCA1, 8 (14%) had variants of unclear significance, 5 (8%) had deleterious mutations in BRCA1. With regard to entry criteria for BRCA1 genetic testing, mutations were detected in 5% (1/20), 2,5% (1/41), 16% (2/12) and 16% (1/6) of women with family history, early onset BC (< 40 years), Breast-Ovarian Cancer (BOC) and early onset plus Bilateral Breast Cancer, respectively. BRCA1 Associated Breast Cancers (BABC) were more likely to have histological grade 3 and high proliferation rate than negative cases (40% v 27%; 60% v 45%). These differences were not statistically significant. BABC were significantly more likely to be estrogen receptor-negative (67% v 16%, P = .04). Though not significant, all valuable tumors with BRCA1 mutations were HER-2/neu negative. In the entire cohort, there were no significant differences between BABC and non-BABC in 5 year relapse free survival (60% v 78%, P = not significant [NS]), 5 year event free survival (60% v 66%, P = NS), or 5 year overall survival. Conclusions: BABC seem to present with adverse molecular and histopathologic features when compared with cases not associated with BRCA1 mutations. However, the prognosis of BABC appears to be similar to that of non associated cancer. No significant financial relationships to disclose.