Immune checkpoint inhibition in early-stage triple-negative breast cancer

Breast cancer cells can evade immune recognition by upregulating programmed death-ligand 1 (PD-L1) leading to decreased T cell function. Anti-PD-1 agents, like pembrolizumab, and anti-PD-L1 agents, such as atezolizumab and durvalumab, in combination with chemotherapy were found to have efficacy in metastatic triple-negative breast cancer (TNBC). With sub-optimal long-term outcomes in early-stage TNBC, this combination of immune checkpoint inhibition with chemotherapy was subsequently investigated. A robust immune microenvironment and extensive tumor antigen exposure in early-stage breast cancer is believed to facilitate response to checkpoint inhibitors.

This review focuses on studies that assess the role of neoadjuvant immune checkpoint inhibition along with chemotherapy. The results of key phase I, II and III trials using checkpoint inhibitors in early-stage breast cancer (ESBC) are reviewed along with foundational data from metastatic TNBC, including the role of biomarkers in predicting response to immunotherapy.

Despite a clear role for neoadjuvant immune checkpoint inhibition in TNBC, many questions remain. The benefit of these agents in the neoadjuvant versus adjuvant setting is unclear and immune-related toxicity is a major concern. Additional studies are needed to elucidate which immune checkpoint inhibitor is most efficacious and best tolerated in early-stage TNBC.