PARP Inhibitors in Breast Cancer: Latest Evidence

Breast cancer treatment continues to evolve as targeted therapeutic strategies are developed for the various molecular subtypes of breast cancer. The PARP inhibitors represent a novel targeted therapy for tumors with defective homologous recombination DNA repair. These agents may become standard new treatment options for patients harboring BRCA1/2 mutations and show promise in BRCA1/2 wild-type patients with triple-negative breast cancers, which are treated predominantly with traditional cytotoxic chemotherapy. This review will discuss the results of clinical trials of these agents in breast cancer as well as important ongoing and anticipated trials. Recent reports support the use of olaparib monotherapy in BRCA1/2-mutated metastatic cancer. Results of PARP inhibitor combinations with chemotherapy have been mixed. The addition of veliparib failed to improve pathological complete response rates in patients with early-stage triple-negative breast cancer treated with carboplatin (AUC6) and paclitaxel followed by doxorubicin plus cyclophosphamide in a phase 3 trial. The PARP inhibitors talazoparib and olaparib are currently being tested in the neoadjuvant and adjuvant settings but impact on survival measures will likely take years prior to reporting in these early-stage breast cancer studies. While data from the first phase 3 trials of PARP inhibitors in breast cancers are encouraging in patients with germline deleterious BRCA1/2 mutations, continued work is needed to elucidate their utility beyond the BRCA1/2-mutated population as has been possible in ovarian cancer. Additionally, defining the ideal population and setting for combination treatment remains a challenge and has been limited by synergistic toxicities.