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

Muenst, S. ; Schaerli, A. ; Gao, F. ; Däster, S. ; Trella, E. ; Droeser, R. ; Muraro, M. ; Zajac, P. ; Zanetti, R. ; Gillanders, W. ; Weber, W. ; Soysal, S.

In: Breast Cancer Research and Treatment, 2014, vol. 146, no. 1, p. 15-24

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    Titre
    • Expression of programmed death ligand 1 (PD-L1) is associated with poor prognosis in human breast cancer
    Auteur
    • Muenst, S.. Institute of Pathology, University Hospital Basel, Schönbeinstrasse 40, CH-4032, Basel, Switzerland
    • Schaerli, A.. Department of Surgery, University Hospital Basel, Basel, Switzerland
    • Gao, F.. Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA
    • Däster, S.. Department of Surgery, University Hospital Basel, Basel, Switzerland
    • Trella, E.. Institute of Surgical Research and Hospital Management (ICFS) and Department of Biomedicine, University of Basel, Basel, Switzerland
    • Droeser, R.. Department of Surgery, University Hospital Basel, Basel, Switzerland
    • Muraro, M.. Institute of Surgical Research and Hospital Management (ICFS) and Department of Biomedicine, University of Basel, Basel, Switzerland
    • Zajac, P.. Institute of Surgical Research and Hospital Management (ICFS) and Department of Biomedicine, University of Basel, Basel, Switzerland
    • Zanetti, R.. Department of Gynecology, University Hospital Basel, Basel, Switzerland
    • Gillanders, W.. Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA
    • Weber, W.. Department of Surgery, University Hospital Basel, Basel, Switzerland
    • Soysal, S.. Department of Surgery, University Hospital Basel, Basel, Switzerland
    Type de document
    • Postprint
    Langue
    • Inglese
    Publié dans
    • Breast Cancer Research and Treatment, 2014, vol. 146, no. 1, p. 15-24. Springer US; http://www.springer-ny.com
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:325732
    Summary
    Recent studies in multiple epithelial cancers have shown thatthe 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.