Metaplastic breast cancers frequently express immune checkpoint markers FOXP3 and PD-L1

Br J Cancer. 2020 Nov;123(11):1665-1672. doi: 10.1038/s41416-020-01065-3. Epub 2020 Sep 17.


Background: Metaplastic breast carcinoma encompasses a heterogeneous group of tumours with differentiation into squamous and/or spindle, chondroid, osseous or rhabdoid mesenchymal-looking elements. Emerging immunotherapies targeting Programmed Death Ligand 1 (PD-L1) and immune-suppressing T cells (Tregs) may benefit metaplastic breast cancer patients, which are typically chemo-resistant and do not express hormone therapy targets.

Methods: We evaluated the immunohistochemical expression of PD-L1 and FOXP3, and the extent of tumour infiltrating lymphocytes (TILs) in a large cohort of metaplastic breast cancers, with survival data.

Results: Metaplastic breast cancers were significantly enriched for PD-L1 positive tumour cells, compared to triple-negative ductal breast cancers (P < 0.0001), while there was no significant difference in PD-L1 positive TILs. Metaplastic breast cancers were also significantly enriched for TILs expressing FOXP3, with FOXP3 positive intra-tumoural TILs (iTILs) associated with an adverse prognostic outcome (P = 0.0226). Multivariate analysis identified FOXP3 iTILs expression status as an important independent prognostic factor for patient survival.

Conclusions: Our findings indicate the clinical significance and prognostic value of FOXP3, PD-1/PD-L1 checkpoint and TILs in metaplastic breast cancer and confirm that a subset of metaplastics may benefit from immune-based therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • B7-H1 Antigen / biosynthesis*
  • Biomarkers, Tumor / immunology*
  • Breast Neoplasms / immunology
  • Breast Neoplasms / pathology*
  • Female
  • Forkhead Transcription Factors / biosynthesis*
  • Humans
  • Immune Checkpoint Inhibitors
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Metaplasia
  • Middle Aged


  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Immune Checkpoint Inhibitors