title: Impact of estrogen receptor-β expression on breast cancer prognosis: a meta-analysis.
abstract: Estrogen receptor (ER)-β has been discovered for decades; however, its prognostic value in breast cancer patients remains controversial. We aimed to evaluate the impact of ER-β expression on breast cancer survival. A systematic search of Medline, Embase, and Cochrane Library was performed to identify the association between ER-β expression and outcomes in early breast cancer patients. Random-effects meta-analysis was conducted to generate combined hazard ratios (HRs) with 95 % confidence intervals (CIs) for overall survival (OS) and disease-free survival (DFS). A total of 6769 patients for ER-β1, 2295 patients for ER-β2, and 2271 patients for ER-β5 from 21 studies were included. ER-β1 protein expression was correlated with both favorable 5-year DFS and OS (HR 0.690, 95 % CI 0.610-0.779; P < 0.001; HR 0.632, 95 % CI 0.533-0.749; P < 0.001), while ER-β1 mRNA had no significant association with DFS (HR 0.915, 95 % CI 0.581-1.440, P = 0.700). ER-β2 protein was associated with improved DFS (HR 0.799, 95 % CI 0.644-0.992; P = 0.042), but not OS (HR 0.958, 95 % CI 0.762-1.205; P = 0.712). ER-β5 protein was not significantly associated with DFS (HR 1.070, 95 % CI 0.810-1.410; P = 0.642). Subgroup analysis showed that higher ER-β1 expression was associated with better 5-year DFS in both ER-α positive and negative patients, but the positive association between ER-β1 expression and 5-year OS was only seen in ER-α positive patients. Wild-type ER-β (ER-β1) and its variant ER-β2 protein expressions are associated with better survival in early breast cancer patients. The prognostic significance of ER-β1 for DFS is independent of ER-α coexpression, whereas the impact on OS was only in ER-α positive breast cancer.
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jieqiong
authors.initials: J
authors.lastname: Liu
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Huishan
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of General Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Mao
authors.affiliation: Department of Urinary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Kan
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Heran
authors.initials: H
authors.lastname: Deng
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. victorlq@hotmail.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017398:Alternative Splicing; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018572:Disease-Free Survival; D047629:Estrogen Receptor beta / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis
chemical_list: D047629:Estrogen Receptor beta
keywords: Breast cancer; Estrogen receptor-β; Meta-analysis; Outcomes