Onkológia 2/2022

The role of PARP inhibitors in the treatment of breast cancer

BRCA1 and BRCA2 are tumor suppressor genes encoding proteins involved in the repair of double strand breaks (DSBs) in s process called homologous recombination repair (HRR). PARP enzymes are the most important enzymes in repairing single strand breaks (SSBs). Tumors with the germline BRCA mutation (gBRCA) are highly sensitive to blockade of PARP enzymes. Olaparib and talazoparib are PARP inhibitors approved in the EU as monotherapy for the treatment of locally advanced/metastatic HER2-negative breast cancer and confirmed gBRCA mutation. The studies showed that they were more effective than chemotherapy, and the time to progression free survival (progression free survival PFS) was prolonged. Treatment was associated with a better side effect profile and a better quality of life (1). The indication for PARP inhibitors is also moving into the adjuvant treatment of breast cancer. Based on phase III results, the OlympiA FDA has approved olaparib in the adjuvant treatment of patients with gBRCA mutant, HER2-negative, high risk breast cancer who have been pre-treated with neoadjuvant or adjuvant chemotherapy (2). By adding PARP inhibitors to the treatment of patients with breast cancer, it is necessary to identify patients who may benefit from this treatment and to provide them with a genetic test.

Keywords: breast cancer, PARP inhibitors, olaparib