Resurrection of PARP Inhibitors in Breast Cancer

Abstract

PARP enzymes are essential for DNA damage repair. Cancers with defective homologous recombination DNA repair, such has BRCA1- and BRCA2-mutated breast cancers, are targets for PARP inhibitors (PARPi) through the exploitation of synthetic lethality. A number of PARPi are currently undergoing clinical evaluation in breast cancer, with olaparib and talazoparib having demonstrated superior efficacy compared with standard chemotherapy in advanced germline BRCA-mutated cancer. This review describes the biological rationale for PARPi and presents the accumulating data on PARPi use in breast cancer.