Emerging strategies for TNBC with early clinical data: new chemoimmunotherapy strategies

Breast Cancer Res Treat. 2022 May;193(1):21-35. doi: 10.1007/s10549-022-06547-x. Epub 2022 Mar 2.

Abstract

Purpose: The use of immune checkpoint inhibitors in combination with chemotherapy for the treatment of triple-negative breast cancer is becoming more widespread as efficacy data accumulates. However, outcomes remain less than optimal and not all patients benefit from treatment. The aim of this article is to review the emerging chemoimmunotherapy strategies for triple-negative breast cancer.

Methods: Searches were undertaken on Pubmed and Clinicaltrials.gov for relevant publications and trials.

Results: Preclinical and clinical data have provided insights into the differing immunomodulatory effects of chemotherapy agents, highlighting the immunostimulatory properties of anthracyclines. Mechanisms of resistance to immune checkpoint inhibition are discussed and the potential role of phosphatidylinositol 3-kinase (PI3K)/AKT and MAPK/ERK kinase (MEK) inhibitors in overcoming resistance. Finally, the emerging therapeutic class of antibody-drug conjugates for triple-negative breast cancer in combination with immune checkpoint inhibitors is reviewed.

Conclusions: The type and sequence of chemotherapy agents play an important role in optimising the response to immune checkpoint inhibitors. Antibody-drug conjugates in combination with immune checkpoint inhibitors are a promising area of development.

Keywords: Advanced TNBC; Antibody–drug conjugates; Early TNBC; Immune checkpoint; Immunotherapy; Targeted therapies.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents* / therapeutic use
  • Humans
  • Immune Checkpoint Inhibitors
  • Immunoconjugates*
  • Phosphatidylinositol 3-Kinase
  • Phosphatidylinositol 3-Kinases
  • Protein Kinase Inhibitors / therapeutic use
  • Triple Negative Breast Neoplasms* / drug therapy

Substances

  • Antineoplastic Agents
  • Immune Checkpoint Inhibitors
  • Immunoconjugates
  • Protein Kinase Inhibitors
  • Phosphatidylinositol 3-Kinase