Molecular features of the basal-like breast cancer subtype based on BRCA1 mutation status

BRCA1-mutated breast cancer is associated with basal-like disease; however, it is currently unclear if the presence of a BRCA1 mutation depicts a different entity within this subgroup. In this study, we compared the molecular features among basal-like tumors with and without BRCA1 mutations. Fourteen patients with BRCA1-mutated (nine germline and five somatic) tumors and basal-like disease, and 79 patients with BRCA1 non-mutated tumors and basal-like disease, were identified from the cancer genome atlas dataset. The following molecular data types were evaluated: global gene expression, selected protein and phospho-protein expression, global miRNA expression, global DNA methylation, total number of somatic mutations, TP53 and PIK3CA somatic mutations, and global DNA copy-number aberrations. For intrinsic subtype identification, we used the PAM50 subtype predictor. Within the basal-like disease, we observed minor molecular differences in terms of gene, protein, and miRNA expression, and DNA methylation variation, according to BRCA1 status (either germinal or somatic). However, there were significant differences according to average number of mutations and DNA copy-number aberrations, and four amplified regions (2q32.2, 3q29, 6p22.3, and 22q12.2), which are characteristic in high-grade serous ovarian carcinomas, were observed in both germline and somatic BRCA1-mutated breast tumors. These results suggest that minor, but potentially relevant, baseline molecular features exist among basal-like tumors according to BRCA1 status. Additional studies are needed to better clarify if BRCA1 genetic status is an independent prognostic feature, and more importantly, if BRCA1 mutation status is a predictive biomarker of benefit from DNA-damaging agents among basal-like disease.