Role of programmed cell death ligand-1 expression on prognostic and overall survival of breast cancer A systematic review and meta-analysis

Background: Recently, the correlation of immunological checkpoint marker programmed cell death ligand-1 (PD-L1) and the prognosis of various cancers has been a research hotspot. The aim of this study is to examine the prognostic effect of PD-L1 in breast cancer. Methods: PubMed, EMBASE, Web of Science, the Cochrane Library database were searched for eligible studies and additional hand-searching were reviewed as an augmentation. Pooled hazard ratios (HR) and 95% confidence interval (CI) for overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS)/recurrence-free survival (RFS), and metastasis-free survival (MFS) were estimated using fixed-or random-effect models. Results: Data from 19 studies involving 12,505 patients were collected. Study quality was assessed according to guidelines for assessing quality in prognostic studies. PD-L1 expression was significantly associated with lymph node metastasis (P<. 001), high tumor grade (P<. 001), negative hormone receptor (P<. 001), human epidermal growth factor receptor 2 (HER2) positivity (P<. 001), high Ki67 (P<. 001), and high tumor-infiltrating lymphocytes (TILs) (P<. 001). PD-L1 expression had no significant impact on CSS (pooled HR 0.83, 95% CI= 0.64-1.09, P=. 19) or MFS (pooled HR 1.11, 95% CI= 0.62-1.97, P=. 72), but significantly correlated with shortened OS (pooled HR 1.52, 95% CI= 1.14-2.03, P=. 004) and DFS (pooled HR 1.31, 95% CI= 1.14-1.51, P<. 000). Subgroup analysis showed that not PD-L1 RNA expression, but protein expression was associated with shorter survival, in addition, the adverse prognostic effect of PD-L1 expression remained in luminal A, luminal B, and HER2 subtype, not in basal-like or triple-negative subtype. Conclusions: An elevated PD-L1 expression significantly correlates with high-risk prognostic indicators and decreased survival in patients with breast cancer.