Prognostic Implications of PD-L1 Expression in Breast Cancer: Systematic Review and Meta-analysis of Immunohistochemistry and Pooled Analysis of Transcriptomic Data

• Published in: Clinical cancer research Vol. 25; no. 18; pp. 5717 - 5726
• Main Authors: Matikas, Alexios, Zerdes, Ioannis, Lövrot, John, Richard, François, Sotiriou, Christos, Bergh, Jonas, Valachis, Antonios, Foukakis, Theodoros
• Format: Journal Article
• Language: English
• Published: United States 15.09.2019
• ISSN: 1078-0432; 1557-3265; 1557-3265
• DOI: 10.1158/1078-0432.CCR-19-1131

Conflicting data have been reported on the prognostic value of PD-L1 protein and gene expression in breast cancer. Medline, Embase, Cochrane Library, and Web of Science Core Collection were searched, and data were extracted independently by two researchers. Outcomes included pooled PD-L1 protein positivity in tumor cells, immune cells, or both, per subtype and per antibody used, and its prognostic value for disease-free and overall survival. A pooled gene expression analysis of 39 publicly available transcriptomic datasets was also performed. Of the initial 4,184 entries, 38 retrospective studies fulfilled the predefined inclusion criteria. The overall pooled PD-L1 protein positivity rate was 24% (95% CI, 15%-33%) in tumor cells and 33% (95% CI, 14%- 56%) in immune cells. PD-L1 protein expression in tumor cells was prognostic for shorter overall survival (HR, 1.63; 95% CI, 1.07-2.46; = 0.02); there was significant heterogeneity ( = 80%, < 0.001). In addition, higher PD-L1 gene expression predicted better survival in multivariate analysis in the entire population (HR, 0.82; 95% CI, 0.74-0.90; < 0.001 for OS) and in basal-like tumors (HR, 0.64; 95% CI, 0.52-0.80; < 0.001 for OS; 0.005). The largest to our knowledge meta-analysis on the subject informs on PD-L1 protein positivity rates and its prognostic value in breast cancer. Standardization is needed prior to routine implementation. PD-L1 gene expression is a promising prognostic factor, especially in basal-like breast cancer. Discrepant prognostic information might be related to PD-L1 gene expression in the stroma.