Development of poly(ADP-ribose) polymerase inhibitors in the treatment of BRCA-mutated breast cancer.

The poly(ADP-ribose) polymerases (PARPs) 1 and 2 are DNA-binding enzymes that play a critical role in the repair of DNA. The use of PARP inhibitors is a rational therapeutic approach to selectively killing a subset of cancer cells with deficiencies in DNA repair pathways. PARP inhibitors that have undergone clinical investigation in the treatment of breast cancer include olaparib, talazoparib, veliparib, niraparib, and rucaparib. The antitumor activity of PARP inhibitors as single agents has been demonstrated in BRCA-associated metastatic breast cancer. In 2018, olaparib became the first oral PARP inhibitor to receive approval in the United States for the treatment of advanced BRCA-mutated breast cancer, an approval that represents a major change in the treatment paradigm for this subtype of breast cancer. PARP inhibition plus chemotherapy and PARP inhibition plus immunotherapy are novel approaches undergoing extensive study in breast cancer. This review focuses on the clinical development of PARP inhibitors administered singly or in combination with other agents for early-stage and metastatic BRCA-mutated breast cancer.