Immune checkpoint inhibitor therapy in breast cancer

Abstract

Initial studies investigating single-agent activity of immune checkpoint inhibitors (ICIs) serve as proof of principle that harnessing the immune system can have anticancer activity in a variety of human malignancies. Although breast cancer was historically believed to be immunogenically silent, early studies indicate overall response rates with ICIs are similar to those observed with many other solid malignancies. Overall response rates in advanced breast cancer are low, but the responses are remarkably durable. A deeper understanding of the biology of the interaction between cancer and immune cells is required to both develop biomarkers that more accurately predict response to therapy and identify effective immunotherapy-based combination strategies that can enhance the immunogenicity of biologically "cold" tumors. Breast cancer encompasses a variety of diseases defined by the presence or absence of central oncogenic drivers, and early data suggest that the distinct subtypes may have unique immune phenotypes. Breast cancer represents an ideal disease in which to investigate immunotherapeutic strategies given the prevalence of the disease, unique clinical trial design opportunities, and immunophenotypic diversity.