Checkpoint blockade in the treatment of breast cancer: current status and future directions

Br J Cancer. 2018 Jul;119(1):4-11. doi: 10.1038/s41416-018-0126-6. Epub 2018 May 29.

Abstract

There is now accumulating evidence that the host immune system plays an important role in influencing response to treatment and prognosis in breast cancer. Immunotherapy with immune checkpoint inhibitors is a promising and rapidly growing field of interest in many solid tumours, including breast cancer. Trials to date have largely focused on metastatic triple-negative disease, a genomically unstable subtype of breast cancer that is believed to be the most immunogenic and following the development of treatment resistance, has limited treatment options and a particularly poor prognosis. Both checkpoint inhibitor monotherapy and combinations with chemotherapy are being investigated. In this review, we discuss the current evidence for PD-1/PD-L1 blockade in metastatic triple-negative breast cancer (TNBC), HER2+ breast cancer and ER+ disease, as well as the emerging evidence for use in the early-stage (neoadjuvant) setting. We also propose potential ways of improving responses to checkpoint blockade in breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / immunology
  • Combined Modality Therapy
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Humans
  • Immunotherapy*
  • Neoadjuvant Therapy / trends
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / immunology
  • Receptor, ErbB-2 / genetics
  • Receptors, Estrogen / genetics
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / immunology
  • Triple Negative Breast Neoplasms / pathology

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Receptors, Estrogen
  • ERBB2 protein, human
  • Receptor, ErbB-2