Prognostic Role of Programmed Death Ligand-1 Expression in Breast Cancer: A Systematic Review and Meta-Analysis.

Abstract

Cancer therapies that target the PD-1/PD-L1 pathway are in ongoing phase I/II clinical trials for several tumor types. However, the prognostic value of PD-L1 expression in breast cancer is unclear. We assessed the prognostic role of PD-L1 expression in breast cancer. We searched Medline/PubMed for eligible studies of the association between PD-L1 expression and patient survival in breast cancer published before 7 December 2015. The effect size was the hazard ratio (HR) with 95% confidence interval (CI) for overall survival (OS), recurrence-free survival (RFS) and metastasis-free survival (MFS). Odds ratios (OR) with 95% CIs were also extracted to evaluate associations between PD-L1 expression and patient clinicopathological features. We included five studies with 7,802 total patients in this meta-analysis. The pooled OR associated high PD-L1 expression with predictors of poor-prognosis: high tumor grade, negative ER status, negative PR status, positive HER2 status and lymphovascular invasion. High PD-L1 protein expression was associated with shorter OS (HR = 3.22, 95% CI: 1.86-5.59; P < 0.0001), shorter RFS (HR = 1.38, 95% CI: 1.03-1.86; P = 0.03) and shorter MFS (HR = 3.33, 95% CI: 2.30-4.82; P < 0.00001); whereas high PD-L1 mRNA expression was associated with longer OS (HR = 0.86, 95% CI: 0.75-1.00; P = 0.05) and longer RFS (HR = 0.57, 95% CI: 0.36-0.91; P = 0.02). The findings of these studies were significantly heterogeneous; the results should be interpreted cautiously. In breast cancer, high PD-L1 protein expression appears to be a negative prognostic factor, whereas high PD-L1 mRNA expression appears to be a favorable prognostic factor.