Prognostic and clinicopathological value of PD-L1 expression in primary breast cancer: a meta-analysis

To evaluate the association between PD-L1 expression (PD-L1+) and clinicopathological characteristics and effect on prognosis in primary breast cancer (PBC). A systematic search of the PubMed, Web of Science, and Embase databases was conducted in November 2018. Studies detecting PD-L1 using immunohistochemistry, and concerning its prognostic or clinicopathological significance in PBC were included. The HR with 95% CI for survival, and the events for clinicopathological features were pooled. Forty-seven studies were included, with a total of 14,367 PBC patients. PD-L1+ tumor cells (TCs) were associated with ductal carcinomas, large tumor size, histological Grade 3 tumors, high Ki-67, ER and PR negative, and triple-negative breast cancer; and also, related to high tumor-infiltrating lymphocytes (TILs) and PD-1 expression. PD-L1+ TCs were significantly associated with shorter disease-free survival (DFS, HR = 1.43, 95% CI 1.21–1.70, P < 0.0001) and overall survival (OS, HR = 1.58, 95% CI 1.14–2.20, P = 0.006). And the HRs of PD-L1+ TCs on DFS and OS were higher (1.48 and 1.70, respectively) and homogeneous when using whole tissue section, compared with tumor microarrays. However, PD-L1+ TILs related to better DFS (HR = 0.45, 95% CI 0.28–0.73, P = 0.001) and OS (HR = 0.41, 95% CI 0.27–0.63, P < 0.0001). PD-L1 expression on TCs associates with high-risk clinicopathological parameters and poor prognosis in PBC patients, while PD-L1+ TILs may relate to a better survival. Comprehensive assessment of TCs and TILs is required when evaluating the clinical relevance of PD-L1 expression in future studies.