PARP inhibitors in the treatment of metastatic breast cancer patients with germline BRCA1/2 mutations. Experience of treatment with talazoparib in clinical practice

Abstract

Germline BRCA1/2 mutations account for about 10% of all breast cancer. BRCA1/2 proteins are involved in homologous recombination - DNA double-strand break repair mechanism. Poly-(ADP ribose) polymerases (PARP) are required to repair DNA single-strand breaks through base excision repair. PARP inhibitors represent a modern option of treatment of metastatic HER2 negative breast cancer with germline BRCA1/2 mutations. Mechanism of action of PARP inhibitors is based on the concept of synthetic lethality under conditions of BRCA dysfunction, when both DNA repair mechanisms, homologous recombination and base excision repair, are impaired. This leads to the apoptosis of cancer cells. Currently two PARP inhibitors are registered in Russia for the treatment of BRCA-associated metastatic HER2 negative breast cancer – olaparib and talazoparib. Efficacy of PARP inhibitors olaparib and talazoparib versus standard chemotherapy has been studied in very similarly designed phase III trials OlympiAD и EMBRACA. Benefit in the progression free survival, acceptable toxicity profile and positive impact on quality of life support inclusion of PARP inhibitors in treatment schemes of metastatic BRCAassociated breast cancer. Very important is the role of PARP inhibitors in treatment of very aggressive triple negative breast cancer with limited number of effective therapy options. We represent here a clinical case of treatment of metastatic triple negative breast cancer with talazoparib in 4th line of therapy.