Poly(ADP-ribose) polymerase inhibitors in the treatment landscape of triple-negative breast cancer (TNBC).

ABSTRACT

OBJECTIVE: Chemotherapy is the mainstay for triple-negative breast cancer (TNBC) patients. Over the years, the use of chemotherapy for these patients has demonstrated many adversities, including toxicity and resistance, which suggested the need to develop novel alternative therapeutic options, such as poly(ADP-ribose) polymerase inhibitors (PARPi). Herein, we provide an overview on PARPi, mechanisms of action and the role of biomarkers in PARPi sensitivity trials, clinical advances in PARPi therapy for TNBC patients based on the most recent studies and findings of clinical trials, and challenges that prevent PARP inhibitors from achieving high efficacy such as resistance and overlapping toxicities with other chemotherapies. DATA SOURCES Searching for relevant articles was done using PubMed and Cochrane Library databases by using the keywords including TNBC; chemotherapy; PARPi; BRCA; homologous recombination repair (HRR). Studies had to be published in full-text in English in order to be considered. DATA SUMMARY: Although PARPi have been used in the treatment of local/metastatic breast malignancies that are HER2 negative and has a germline BRCA mutation, several questions are still to be answered in order to maximize the clinical benefit of PARP inhibitors in TNBC treatment, such as questions related to the optimal use in the neoadjuvant and metastatic settings as well as the best combinations with various chemotherapies. CONCLUSIONS: PARPi are emerging treatment options for patients with gBRCA1/2 mutations. Determining patients that are most likely to benefit from PARPi and identifying the optimal treatment combinations with high efficacy and fewer side effects are currently ongoing.