High-grade serous ovarian cancer (HGSC) remains the deadliest gynecological cancer due to presentation at advanced stage with metastatic disease; eventually become drug chemotherapy resistant. Triple negative breast cancer (TNBC) is a similarly aggressive tumor with poor prognosis. HGSC and TNBC are genomically unstable due to loss-of-function mutations in BRCA1, BRCA2, PALB2, ATM, RAD51 and TP53 genes involved in DNA damage response. These breast and ovarian cancer susceptibility genes also regulate cellular metabolism, growth, stemness, antioxidant and detoxification processes. Black and Ashkenazi Jewish women are at increased risk for developing these diseases. The HBOC laboratory uses molecular epidemiology, translational and basic sciences techniques to study disease pathogenesis in hereditary and sporadic HGSC and TNBC in these populations.