Immune Checkpoint Blockade in Hormone Receptor-Positive Breast Cancer: Resistance Mechanisms and Future Perspectives

Anti-programmed cell death protein 1 immunotherapy has been incorporated in the treatment algorithm of triple-negative breast cancer (TNBC). However, clinical trial results for patients with hormone receptor (HR)-positive disease appear less compelling. HR-positive tumors exhibit lower levels of programmed death-ligand 1 expression in comparison with their triple-negative counterparts. Moreover, signaling through estrogen receptor alters the immune microenvironment, rendering such tumors immunologically "cold." To explain differential responses to immune checkpoint blockade, this review interrogates differences between HR-positive and TNBC. Starting from distinct genomic features, we further present disparities concerning the tumor microenvironment and finally, we summarize early-phase clinical trial results on promising novel immunotherapy combinations.