Analysis of BRCA1-related functional associations in sporadic triple negative breast cancer: A network-based approach.

1070Background: Sporadic triple negative breast cancers (TNBC) are aggressive malignancies that present a yet unaddressed clinical challenge. They are refractory to hormonal and HER2-targeted therapy, leaving chemotherapy as the mainstay of systemic treatment. Their striking resemblance to BRCA1-mutated hereditary breast cancers has led to the speculation that BRCA1 pathway derangement underlies sporadic TNBC and could be exploited therapeutically. BRCA1 has been implicated in multiple cellular processes via interactions with diverse partner proteins. Methods: To search for TNBC-specific aberrations within the complex array of BRCA1-related functional associations, we devised a strategy that takes into account the versatility of the BRCA1 protein and combines database mining, literature curation, network modeling, and transcriptome analysis. Results: We used database- and literature-derived data on protein-protein interactions, co-complex memberships, and biochemical modifications involving BRCA1 to build...