Checkpoint inhibitor therapy for metastatic triple-negative breast cancer

Cancer Metastasis Rev. 2021 Jun;40(2):537-547. doi: 10.1007/s10555-021-09972-4. Epub 2021 Jun 8.


Immunotherapy has become a mainstay of cancer treatment in many malignancies, though its application in breast cancer remains limited. Of the breast cancer subtypes, triple-negative breast cancers (TNBCs) are characterized by immune activation and infiltration and more commonly express biomarkers associated with response to immunotherapy. Checkpoint inhibitor therapy has shown promising activity in metastatic TNBC. In 2019, the US FDA granted accelerated approval of atezolizumab, a programmed death-ligand 1 (PD-L1) inhibitor, in combination with nab-paclitaxel for unresectable locally advanced or metastatic PD-L1-positive TNBC, based on the results of the phase III IMpassion130 trial. In 2020, the FDA also granted accelerated approval of pembrolizumab, a PD-1 inhibitor, in combination with chemotherapy for locally recurrent unresectable and metastatic PD-L1-positive TNBC, based on results of the phase III KEYNOTE-355 trial. Additional combination strategies are being explored in the treatment of metastatic TNBC, with the goal of augmenting antitumor activity. In this review, the clinical development of checkpoint inhibitors in the treatment of metastatic TNBC will be discussed, including clinical outcomes with monotherapy and combination therapy regimens, biomarkers that may predict for benefit, and future directions in the field.

Keywords: Checkpoint inhibitor; Immunotherapy; Metastatic; Review; Triple-negative breast cancer.

Publication types

  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Clinical Trials, Phase III as Topic
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / administration & dosage
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Neoplasm Metastasis
  • Randomized Controlled Trials as Topic
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / immunology*


  • Immune Checkpoint Inhibitors