Targeted Therapies and the Evolving Standard of Care for Triple-Negative and Germline BRCA1/2-Mutated Breast Cancers in the High-Risk, Early-Stage Setting.

Abstract

Immune checkpoint inhibitors (ICIs) and poly (ADP-ribose) polymerase (PARP) inhibitors have transformed the treatment landscape of metastatic triple-negative breast cancer (TNBC). Trial results have demonstrated the clinical benefit of these targeted agents in the advanced TNBC setting and have led to their evaluation in the treatment of high-risk, early-stage TNBC and BRCA-mutated breast cancer. We provide a summary of the results that have led to the establishment of the ICI pembrolizumab and the PARP inhibitor olaparib as new standards of care. Using PubMed, we searched for original articles published in English between 2017 and 2022. Search terms included triple-negative breast cancer, adjuvant, neoadjuvant, immunotherapy, and PARP inhibitors. Two targeted therapies have been approved by the US Food and Drug Administration for the treatment of TNBC and BRCA-mutated breast cancers in the high-risk, early-stage setting on the basis of clinical trial results demonstrating improved clinical outcomes. For high-risk, early-stage TNBC, pembrolizumab was approved as neoadjuvant therapy in combination with chemotherapy and as a single agent for continued treatment after surgery; this approval was based on results of the KEYNOTE-522 trial. Olaparib was approved for the adjuvant treatment of patients with high-risk, early-stage human epidermal growth factor receptor type 2 (HER2)-negative breast cancer with germline BRCA1/2 mutations who have been previously treated with neoadjuvant or adjuvant chemotherapy on the basis of the OlympiA trial results. Clinical trial results demonstrate the pronounced clinical benefits of pembrolizumab combined with chemotherapy for high-risk, early-stage TNBC and adjuvant olaparib for high-risk, early-stage HER2-negative BRCA1/2-mutated breast cancer.