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

  • Epidemiology
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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.

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Acknowledgments

This work was supported by Grant [2013]163 from Key Laboratory of Malignant Tumor Molecular Mechanism and Translational Medicine of Guangzhou Bureau of Science and Information Technology; Grant KLB09001 from the Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes; Grant from Guangdong Science and Technology Department (2015B050501004). We thank Dr. Lisa K. Jacobs and Dr. Min Ji Kim for the English editing of this manuscript.

Author Contributions

J. Liu carried out the data collection and analysis, participated in the design of the study, and drafted the manuscript. H. Guo participated in data collection, analysis, and manuscript writing. K. Mao carried out the data collection and analysis. K. Zhang participated in the data analysis. H. Deng participated in the manuscript writing. Q. Liu carried out the study design and coordination, and helped to draft the manuscript.

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    Authors and Affiliations

    1. 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

      Jieqiong Liu, Huishan Guo, Heran Deng & Qiang Liu

    2. Department of General Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China

      Kai Mao

    3. Department of Urinary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China

      Kan Zhang

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    1. Jieqiong Liu
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    Correspondence to Qiang Liu.

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    Jieqiong Liu and Huishan Guo contributed equally to this study.

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    Figure S1: Forest plot of association between ER-β1 protein and 5-year OS of breast cancer patients, when only studies with the same cut-off (10 %) of ER-β1 were included

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    Figure S2: Forest plot of association between ER-β2 protein and 5-year OS of breast cancer patients, when one study contained both nuclear and cytoplasmic ER-β2 expression data was excluded

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    Liu, J., Guo, H., Mao, K. et al. Impact of estrogen receptor-β expression on breast cancer prognosis: a meta-analysis. Breast Cancer Res Treat 156, 149–162 (2016). https://doi.org/10.1007/s10549-016-3721-3

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