[Show abstract][Hide abstract] ABSTRACT: Gene expression profiles stratify breast cancer into subtypes suggested to reflect distinct cellular origin and divergent tumor progression1. Inherited mutations in breast cancer early-onset genes BRCA1 and BRCA2 confer high risk of disease. These genes encode multi-functional proteins involved in cell-cycle control and genomic damage response pathways, and loss of function may shape tumor progression and phenotype as suggested by specific hallmarks of hereditary tumors2. It is unclear to what extent sporadic breast cancers phenotypically converge with hereditary cases and if resemblance provides insight to initiation and progression. Herein, we report molecular profiles of breast cancers and demonstrate similarities between tumors from BRCA1 mutation carriers and a molecularly homogenous entity characterized by basal-like phenotype, high degree of genomic imbalances, and BRCA1 promoter methylation. We show that whereas tumors from BRCA2 mutation carriers are more heterogeneous, a substantial fraction resembles an entity characterized by luminal B phenotype and elevated frequency of EMSY amplifications. This has implications for our understanding of the breast cancer hierarchy and disease management.