Estrogen receptor beta as a prognostic factor in breast cancer patients: A systematic review and meta-analysis
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Weige Tan1,2*, Qian Li1,2*, Kai Chen1,2, Fengxi Su1,2, Erwei Song1,2,3 and Chang Gong1,2
1 Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
2 Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
3 Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
* These authors have contributed equally to this work
Chang Gong, email:
Erwei Song, email:
Keywords: estrogen receptor beta, breast cancer, survival, endocrine therapy, prognostic factor
Received: October 11, 2015 Accepted: January 24, 2016 Published: February 06, 2016
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.
Method: 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.
Conclusion: 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.
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