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Expression of programmed death ligand 1 (PD-L1) is associated with poor prognosis in human breast cancer

2014; Springer Science+Business Media; Volume: 146; Issue: 1 Linguagem: Inglês

10.1007/s10549-014-2988-5

1573-7217

Simone Muenst, A. R. Schaerli, Feng Gao, Silvio Däster, Emanuele Trella, Raoul A. Droeser, Manuele Giuseppe Muraro, Paul Zajac, Rosanna Zanetti, W.E. Gillanders, William P. Weber, Savas D. Soysal,

HER2/EGFR in Cancer Research

Recent studies in multiple epithelial cancers have shown that the inhibitory receptor programmed cell death 1 (PD-1) is expressed on tumor-infiltrating lymphocytes and/or programmed death ligand 1 (PD-L1) is expressed on tumor cells, suggesting that antitumor immunity may be modulated by the PD-1/PD-L1 signaling pathway. In addition, phase 1 clinical trials with monoclonal antibodies targeting PD-1 or PD-L1 have shown promising results in several human cancers. The purpose of this study was to investigate the impact of PD-L1 expression in human breast cancer specimens. We conducted an immunohistochemistry study using a tissue microarray encompassing 650 evaluable formalin-fixed breast cancer cases with detailed clinical annotation and outcomes data. PD-L1 was expressed in 152 (23.4 %) of the 650 breast cancer specimens. Expression was significantly associated with age, tumor size, AJCC primary tumor classification, tumor grade, lymph node status, absence of ER expression, and high Ki-67 expression. In univariate analysis, PD-L1 expression was associated with a significantly worse OS. In multivariate analysis, PD-L1 expression remained an independent negative prognostic factor for OS. In subset analyses, expression of PD-L1 was associated with significantly worse OS in the luminal B HER2− subtype, the luminal B HER2+ subtype, the HER2 subtype, and the basal-like subtype. This is the first study to demonstrate that PD-L1 expression is an independent negative prognostic factor in human breast cancer. This finding has important implications for the application of antibody therapies targeting the PD-1/PD-L1 signaling pathway in this disease.