Impact of estrogen receptor-β expression on breast cancer prognosis: a meta-analysis

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.