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

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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.

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Acknowledgments

The authors wish to acknowledge the support of the Biostatistics Core, Siteman Comprehensive Cancer Center WUSM, and NCI Cancer Center Support Grant P30 CA091842.

We thank Professor Alexandar Tzankov for his contribution to the development of the PD-L1 immunohistochemical assay as well as his valuable insights and critical review of the manuscript. We also thank Professor Giulio Spagnoli for his support and critical evaluation of the manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Institute of Pathology, University Hospital Basel, Schönbeinstrasse 40, CH-4032, Basel, Switzerland

    S. Muenst

  2. Department of Surgery, University Hospital Basel, Basel, Switzerland

    A. R. Schaerli, S. Däster, R. A. Droeser, W. P. Weber & S. D. Soysal

  3. Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA

    F. Gao

  4. Institute of Surgical Research and Hospital Management (ICFS) and Department of Biomedicine, University of Basel, Basel, Switzerland

    S. Däster, E. Trella, R. A. Droeser, M. G. Muraro, P. Zajac & S. D. Soysal

  5. Department of Gynecology, University Hospital Basel, Basel, Switzerland

    R. Zanetti

  6. Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA

    W. E. Gillanders

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  1. S. Muenst
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  2. A. R. Schaerli
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  3. F. Gao
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  4. S. Däster
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  12. S. D. Soysal
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Corresponding author

Correspondence to S. Muenst.

Additional information

S. Muenst and A. R. Schaerli have contributed equally to this study.

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Muenst, S., Schaerli, A.R., Gao, F. et al. Expression of programmed death ligand 1 (PD-L1) is associated with poor prognosis in human breast cancer. Breast Cancer Res Treat 146, 15–24 (2014). https://doi.org/10.1007/s10549-014-2988-5

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  • DOI: https://doi.org/10.1007/s10549-014-2988-5

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