title: 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.
authors.affiliation: Department of Radiation Oncology and Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, 300060, China.|Department of Radiation Oncology, Shandong Cancer Hospital affiliated to Shandong University, Shandong Academy of Medical Science, Jinan, 250000, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, Shandong Cancer Hospital affiliated to Shandong University, Shandong Academy of Medical Science, Jinan, 250000, China.
authors.forename: Minghuan
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology and Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, 300060, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Lian
authors.affiliation: Department of Radiation Oncology, Shandong Cancer Hospital affiliated to Shandong University, Shandong Academy of Medical Science, Jinan, 250000, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Radiation Oncology, Shandong Cancer Hospital affiliated to Shandong University, Shandong Academy of Medical Science, Jinan, 250000, China.
authors.forename: Li
authors.initials: L
authors.lastname: Kong
authors.affiliation: Department of Radiation Oncology and Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, 300060, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology and Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, 300060, China. sdyjmdoctor@163.com.|Department of Radiation Oncology, Shandong Cancer Hospital affiliated to Shandong University, Shandong Academy of Medical Science, Jinan, 250000, China. sdyjmdoctor@163.com.
authors.forename: Jinming
authors.initials: J
authors.lastname: Yu
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D006801:Humans; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics*
chemical_list: C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor