Unlocking Therapeutic Potential of Poly(Adenosine Diphosphate Ribose) Polymerase (PARP) Inhibitors in Metastatic Breast Cancer With BRCA Gene Mutations: A Narrative Review.

ABSTRACT

Breast cancer (BC), a significant global health concern, impacts millions of women worldwide. A key genetic factor in this disease is the presence of BReast CAncer gene (BRCA) mutations, which increase susceptibility to BC. This narrative review explores the crucial role of poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors in treating metastatic BC in individuals with BRCA gene mutations. In BRCA mutation carriers, these inhibitors induce synthetic lethality, leading to cell death due to the accumulation of lethal DNA breaks. Clinical trials have demonstrated the effectiveness of PARP inhibitors, such as olaparib and talazoparib, in extending progression-free survival and response rates, especially in patients without prior chemotherapy. Moreover, this review discusses combination therapies, where PARP inhibitors are combined with cytostatic drugs like platinum-based chemotherapy. Some studies show the synergy of these approaches, even in patients without homologous recombination deficiency. In summary, PARP inhibitors offer hope for improving outcomes in metastatic BC patients with BRCA gene mutations. As research advances, PARP inhibitors continue to hold promise in the fight against BC.