期刊
BRITISH JOURNAL OF CANCER
卷 123, 期 11, 页码 1665-1672出版社
SPRINGERNATURE
DOI: 10.1038/s41416-020-01065-3
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资金
- National Breast Cancer Foundation [PRAC-16-006, IIRS-19-084]
- Sydney Breast Cancer Foundation
- Pathology Queensland-Study Education and Research Committee
- NHMRC [APP1113867]
- Cancer Australia/National Breast Cancer Foundation PdCCRS grant [APP1082435]
- National Breast Cancer Foundation [IIRS-19-084, PRAC-16-006] Funding Source: researchfish
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.
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