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

Clin Breast Cancer. 2022 Oct;22(7):642-649. doi: 10.1016/j.clbc.2022.06.004. Epub 2022 Jul 7.

Abstract

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.

Keywords: Estrogen receptor; Immunotherapy; PD-1; PD-L1.

Publication types

  • Review

MeSH terms

  • B7-H1 Antigen / metabolism
  • Hormones
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immunotherapy / methods
  • Receptors, Estrogen
  • Triple Negative Breast Neoplasms* / pathology
  • Tumor Microenvironment

Substances

  • B7-H1 Antigen
  • Hormones
  • Immune Checkpoint Inhibitors
  • Receptors, Estrogen