Immune checkpoint inhibitors in breast cancer: development, mechanisms of resistance and potential management strategies

Abstract

The use of immune checkpoint inhibitors (ICIs) has increased exponentially in the past decade, although its progress specifically for breast cancer has been modest. The first U.S. Food and Drug Administration approval for ICI in breast cancer came in 2019, eight years after the first-ever approval of an ICI. At present, current indications for ICIs are relevant only to a subset of patients with triple-negative breast cancer, or those displaying high microsatellite instability or deficiency in the mismatch repair protein pathway. With an increasing understanding of the limitations of using ICIs, which stem from breast cancer being innately poorly immunogenic, as well as the presence of various intrinsic and acquired resistance pathways, ongoing trials are evaluating different combination therapies to overcome these barriers. In this review, we aim to describe the development timeline of ICIs and resistance mechanisms limiting their utility, and summarise the available approaches and ongoing trials relevant to overcoming each resistance mechanism.