Special considerations for patients with germline BRCA1/BRCA2 variants

Germline variants in BRCA1 or BRCA2 are present in 4% to 8% of patients with pancreatic adenocarcinoma.[11,12] BRCA1/BRCA2 encode for proteins in the homologous repair pathway and DNA double-stranded break repair, and thus may be more sensitive to further DNA damage. Pancreatic tumors with BRCA1/BRCA2 variants demonstrate improved responses to platinum-based therapies.[13] Poly (ADP-ribose) polymerase (PARP) inhibition has been posited to act synergistically with BRCA1/BRCA2 variants by inhibiting single-stranded break repair. Several PARP inhibitors have been approved for treatment of patients with BRCA1/BRCA2-mutated advanced ovarian and breast cancers and are actively being studied for the management of patients with BRCA1/BRCA2-mutated pancreatic adenocarcinoma.