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

Abstract

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.

Conflict of interest statement

Conflict of interest The authors declare that they have no conflict of interest.

Figures

Fig. 1

Representative photographs of PD-L1 expression in breast cancer tissue punches a Tissue punch negative for PD-L1 expression. Magnification ×200 b Tissue punch with strong PD-L1 expression in 100 % of cells. Magnification ×200 c Same tissue punch as in b magnification ×400. d Tissue punch with strong PD-L1 expression in 40 % of cells. Magnification ×200

Fig. 2

a Kaplan–Meier survival curve for overall survival depending on the expression of PD-L1 (univariate analysis) b–f Kaplan–Meier survival curves for overall survival depending on the expression of PD-L1 for the indicated breast cancer intrinsic subtypes

Fig. 3

Representative flow cytometry data for PD-L1 expression in human breast cancer a stage IV breast cancer b stage I breast cancer