The role of immune checkpoint inhibitors in triplenegative breast cancer: recent developments and future perspectives

Abstract

Triple-negative breast cancer (TNBC) represents the subtype of breast cancer with the most aggressive biological behavior and the worst prognosis compared to other breast cancers. Metastatic TNBC is characterized by a high proliferative index, rapid progression with metastases to the viscera and central nervous system, and generally an unfavorable prognosis with a survival of about one year. It is, therefore, necessary to identify specific targets and more effective treatments for patients with TNBC. Evidence of the effect of the tumor immune microenvironment on clinical outcomes is considered a significant issue in breast cancer therapeutics. Compared to other subtypes of breast cancer, TNBC is characterized by a higher mutational burden and is recognized as the most immunogenic among them. Based on these findings, immune checkpoint inhibition was evaluated in TNBC with encouraging results. Indeed, enhancing antitumor immunity in TNBC by blocking the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) axis or the programmed cell death-1 (PD-1) receptor/programmed death-ligand 1 (PD-L1) pathway is a promising treatment option. In this review, we examine the role of monoclonal antibodies targeting CTLA-4 and PD-1/PD-L1 in this breast cancer subtype and discuss combination approaches for early and advanced disease.