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


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.

Type Journal
ISBN 1532-1827 (Electronic) 0007-0920 (Linking)
Authors Kalaw, E.; Lim, M.; Kutasovic, J. R.; Sokolova, A.; Taege, L.; Johnstone, K.; Bennett, J.; Saunus, J. M.; Niland, C.; Ferguson, K.; Gresshoff, I.; Bettington, M.; Pathmanathan, N.; Tse, G. M.; Papadimos, D.; Pathmanathan, R.; Harris, G.; Yamaguchi, R.; Tan, P. H.; Fox, S.; O'Toole, S. A.; Simpson, P. T.; Lakhani, S. R.; McCart Reed, A. E.
Responsible Garvan Author Prof Sandra O'Toole
Publisher Name British Journal of Cancer
Published Date 2020-11-01
Published Volume 123
Published Issue 11
Published Pages 1665-1672
Status Published in-print
DOI 10.1038/s41416-020-01065-3
URL link to publisher's version