Immunophenotypic and pathologic differences between BRCA1 and BRCA2 hereditary breast cancers

Morphologically and clinically, breast cancer is a heterogeneous group of diseases. This heterogeneity may be a manifestation of differences in the molecular genetic events underlying distinct breast cancer pathogenesis pathways. Examination of hereditary breast cancers (HBC), which have in common an underlying germline mutation in BRCA1 or BRCA2, may provide further insight into this concept. Multiple studies have confirmed that BRCA1-associated HBC (BRCA1-HBC) generally exhibit a specific phenotype that is characterized by high tumor grade and estrogen receptor negativity. Conversely, discrepancies exist between the findings of studies that have examined BRCA2-HBC, and a specific phenotype has not been consistently described. The characteristic phenotype of BRCA1-associated tumors may prove a useful additional tool in selecting individuals with breast cancer who should be offered BRCA1 mutation testing, although further studies are required. Lastly, evidence is emerging to suggest that BRCA1 might be involved in the pathogenesis of a subgroup of non-HBC (by gene underexpression rather than mutation) and that these tumors may exhibit the same phenotype as their hereditary counterparts.