A narrative review of immune checkpoint inhibitors in early stage triple negative breast cancer

Abstract

Triple negative breast cancer (TNBC) is an aggressive disease characterized by heterogeneous molecular and immunological characteristics that portends worse overall survival compared to other breast cancer subtypes. Until now, chemotherapy has remained the cornerstone of TNBC treatment despite recent efforts to explore new molecularly targeted therapeutic targets and personalized treatments. Given TNBC has a more immunogenic tumor microenvironment than other breast cancer subtypes, there is hope that immunotherapy will emerge as a new pillar of treatment in TNBC. Based on the IMPASSION130 and KEYNOTE-355 studies, the combination of nab-paclitaxel plus atezolizumab, and chemotherapy plus pembrolizumab, respectively, have been approved by the Food and Drug Administration for locally recurrent, unresectable, or metastatic TNBC in the first line setting. Several studies have now been published demonstrating PD-1/PD-L1 inhibitors given alongside neoadjuvant taxane and anthracycline-based chemotherapy with or without a platinum agent significantly improves pathologic complete response rate. The choice of chemotherapy given in cooperation with PD-1/PD-L1 checkpoint inhibitor seems to determine the amount benefit derived from immunotherapy. However, longer term follow-up is required to ascertain whether immunotherapy, specifically PD-1/PD-L1 blockade, will improve event-free survival and overall survival. Future studies are underway investigating the role of immunotherapy in the adjuvant setting and in patients with residual disease after neoadjuvant therapy. Other unanswered questions remain including the total duration of immunotherapy, and which patient population would benefit from these expensive and sometimes toxic therapies. This narrative review aims to provide insight on the current landscape of immune checkpoint inhibitors in early TNBC.