| Summary: | Inhibitors of poly(ADP-ribose) polymerase (PARP), such as olaparib and talazoparib, have recently been approved as therapies for BRCA-mutated human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (BC). In addition, olaparib, as well as rucaparib and niraparib, have received approval for treatment of patients with BRCA-mutated or platinum-sensitive recurrent ovarian cancer.
The treatment efficacy of PARP inhibitors is higher in case of malignancies that harbour deleterious germline or somatic BRCA mutations compared to BRCA wild-type tumours. Consequently, BRCA mutations or intrinsic tumour sensitivity to platinum therapy are considered indicators of impaired ability to repair DNA double-strand breaks via homologous recombination.
However, not all BRCA-mutated cancer patients benefit from PARP inhibitors. In contrast, for some patients with wild-type BRCA or platinum-resistant tumours, the PARP inhibitors may still offer some therapeutic advantages. Therefore, there is a need to determine additional biomarkers to more precisely select patients without deleterious BRCA mutations, who may be eligible for treatment with PARP inhibitors.
The main objective of this mini-review is to present the main mechanisms of action of PARP inhibitors and briefly summarise the clinical trials leading to their approval in treatment of BRCA-mutated, HER2-negative metastatic BC. In addition, this article discusses the efficacy, safety, and resistance to PARP inhibitors in women with metastatic BC.
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