BRCA1 and BRCA2 Cancer Syndromes and Clinical Significance

Abstract

Familial breast and ovarian cancers are associated with BRCA1 and/or BRCA2 gene germline mutations in chromosomes 17 and 13, respectively. Diagnosis of BRCA1/2 tumor syndromes is made through genetic testing in a clinically approved laboratory. BRCA1 mutation associates with early onset of breast cancer with aggressive nature in female patients. It is often ductal phenotype expressing basal-like biomarkers, with high nuclear grade, pushing or circumscribed borders and associates with marked lymphocytic infiltrate with/without geographic necrosis. In contrast, there is greater representation of BRCA2 tumors and underrepresentation of BRCA1 tumors in male breast cancer patients. Luminal phenotype is the most common molecular subtype in male breast cancer, with invasive ductal carcinoma of no special type being the most common histological subtype seen in familial male breast cancer patients. Although recent studies suggest that prostate cancer and pancreatic cancer may also be associated with increased risk in BRCA mutation carriers, the mechanism of tumorigenesis remains unrevealed. Compared with increased surveillance to maximize early detection and chemoprevention, prophylactic surgery remains the most effective method to reduce cancer risk in BRCA mutation carriers; however, only some BRCA mutation carriers elect to undergo prophylactic surgery.