title: The Prognostic Value of Forkhead Box P3 Expression in Operable Breast Cancer: A Large-Scale Meta-Analysis.
abstract: BACKGROUND
  Recent studies have shown that the forkhead box P3 (FOXP3) protein has a prognostic role in breast cancer. However, these results are controversial. Therefore, the aim of this meta-analysis was to clarify the prognostic role of FOXP3 expression in operable breast cancer cases.
  
  
  METHODS
  Eligible studies describing the use of FOXP3 as a prognostic factor for operable breast cancer cases were identified. Clinicopathological features, disease-free survival (DFS), and overall survival (OS) data were collected from these studies and were analyzed using Stata software.
  
  
  RESULTS
  A total of 16 articles containing data from 13,217 breast cancer patients met the inclusion criteria established for this study. The subsequent meta-analysis that was performed showed that high levels of FOXP3 are not significantly associated with DFS and OS with significant heterogeneity. An additional subgroup analysis demonstrated that intratumoral FOXP3+ regulatory T cells (Tregs) were positively correlated with adverse clinicopathological parameters, yet they did not show an association with DFS or OS. For tumor cells, the pooled results revealed that FOXP3 is significantly associated with DFS (HR: 2.55, 95% CI: 1.23-5.30) but is not associated with clinicopathological parameters or OS. We also observed a significant correlation between FOXP3 expression and survival in the estrogen receptor-positive (ER)+ subgroup (HR: 1.83, 95% CI: 1.36-2.47 for DFS, HR: 1.87, 95% CI 1.28-2.73 for OS), in the Asian region (HR: 1.98, 95% CI: 1.56-2.50 for DFS, HR: 1.93, 95% CI: 1.12-3.35 for OS) and using the median as the FOXP3-positive cut-off value (HR: 1.94, 95% CI: 1.57-2.39 for DFS, HR: 2.06; 95% CI: 1.36-3.11 for OS).
  
  
  CONCLUSIONS
  This meta-analysis indicates that a prognostic role for FOXP3 expression in operable breast cancer cases depends on the FOXP3-positive region, ER status, geographic region and the FOXP3-positive cut-off value.
authors: Department of Oncology, Shanghai Sixth People's Hospital East Campus, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors: Shu Chen
authors: SC
authors: Lin
authors: Department of Oncology, Shanghai Sixth People's Hospital East Campus, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors: Zhi Hua
authors: ZH
authors: Gan
authors: Department of Oncology, The Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors: Yang
authors: Y
authors: Yao
authors: Department of Oncology, Shanghai Sixth People's Hospital East Campus, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors: Da Liu
authors: da L
authors: Min
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery*; D018572:Disease-Free Survival; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D011379:Prognosis; D017594:Publication Bias; D011960:Receptors, Estrogen / Q000378:metabolism
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D011960:Receptors, Estrogen