title: Estrogen receptor beta as a prognostic factor in breast cancer patients: A systematic review and meta-analysis.
abstract: BACKGROUND
  The prognostic role of estrogen receptor beta (ERβ) in early-stage breast cancer is unclear. We performed a systematic review and meta-analysis to evaluate the prognostic value of ERβ in early-stage breast cancer patients.
  
  
  METHODS
  We searched Medline, Embase, and the Web of Science for studies published between 1990 and 2015 that assessed ERβ status in breast cancer patients. A total of 25 studies comprising 9919 patients fitting our inclusion and exclusion criteria were included. The hazard ratios of ERβ status were extracted for diseases free survival (DFS)/ ) and overall survival (OS). Random or fixed-effects models were used when appropriate, and between-study heterogeneity was assessed.
  
  
  RESULTS
  In the 20 studies that assessed ERβ status using immunohistochemical (IHC) methods, we observed significantly improved DFS in patients positive for ERβ-1 (HR=0.56, 95%CI 0.40-0.78, P=0.0007) and ERβ-2 (HR=0.67, 95%CI 0.45-1.00, P=0.05). Improved OS was associated with a positive status for pan-ERβ (HR=0.60, 95%CI 0.45-0.80, P=0.0004) and ERβ-2 (HR=0.44, 95%CI 0.31-0.62, P<0.0001). In ERα-positive patients, ERβ positivity was not associated with DFS (HR=0.77, 95%CI 0.46-1.27, P=0.31) or OS (HR=0.64, 95%CI 0.37-1.11, P=0.11). In contrast, ERβ expression was significantly associated with increased DFS (HR=0.37, 95%CI 0.14-0.93, P=0.03) or OS (HR=0.44, 95%CI 0.30-0.65, P<0.0001) in ERα-negative patients. We did not observe an association between ERβ mRNA levels and DFS and OS.
  
  
  CONCLUSIONS
  In this study, we showed that IHC ERβ status, rather than mRNA levels, is a prognostic factor that is associated with DFS and OS in breast cancer patients. The prognostic value of ERβ may be higher in ERα-negative patients than in ERα-positive patients.
authors: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.|Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
authors: Weige
authors: W
authors: Tan
authors: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.|Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
authors: Qian
authors: Q
authors: Li
authors: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.|Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
authors: Kai
authors: K
authors: Chen
authors: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.|Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
authors: Fengxi
authors: F
authors: Su
authors: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.|Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors: Erwei
authors: E
authors: Song
authors: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.|Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
authors: Chang
authors: C
authors: Gong
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality*; D018572:Disease-Free Survival; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D012333:RNA, Messenger
keywords: breast cancer; endocrine therapy; estrogen receptor beta; prognostic factor; survival