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

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

Research output: Contribution to journalArticlepeer-review

309 Scopus citations

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.

Original languageEnglish
Pages (from-to)15-24
Number of pages10
JournalBreast Cancer Research and Treatment
Volume146
Issue number1
DOIs
StatePublished - Jul 2014

Keywords

  • PD-1
  • PD-L1
  • Prognostic factor
  • TIL
  • Tumor immunology breast cancer

Fingerprint Dive into the research topics of 'Expression of programmed death ligand 1 (PD-L1) is associated with poor prognosis in human breast cancer'. Together they form a unique fingerprint.

Cite this