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摘要
Estrogen receptor (ER)-beta has been discovered for decades; however, its prognostic value in breast cancer patients remains controversial. We aimed to evaluate the impact of ER-beta expression on breast cancer survival. A systematic search of Medline, Embase, and Cochrane Library was performed to identify the association between ER-beta 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-beta 1, 2295 patients for ER-beta 2, and 2271 patients for ER-beta 5 from 21 studies were included. ER-beta 1 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-beta 1 mRNA had no significant association with DFS (HR 0.915, 95 % CI 0.581-1.440, P = 0.700). ER-beta 2 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-beta 5 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-beta 1 expression was associated with better 5-year DFS in both ER-alpha positive and negative patients, but the positive association between ER-beta 1 expression and 5-year OS was only seen in ER-alpha positive patients. Wild-type ER-beta (ER-beta 1) and its variant ER-beta 2 protein expressions are associated with better survival in early breast cancer patients. The prognostic significance of ER-beta 1 for DFS is independent of ER-alpha coexpression, whereas the impact on OS was only in ER-alpha positive breast cancer.
