Estrogen receptor beta as a prognostic factor in breast cancer patients: A systematic review and meta-analysis

Background: The prognostic role of estrogen receptor beta (ER beta) in early-stage breast cancer is unclear. We performed a systematic review and meta-analysis to evaluate the prognostic value of ER beta 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 ER beta 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 ER beta 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 ER beta status using immunohistochemical (IHC) methods, we observed significantly improved DFS in patients positive for ER beta-1 (HR=0.56, 95% CI 0.40-0.78, P=0.0007) and ER beta-2 (HR=0.67, 95% CI 0.45-1.00, P=0.05). Improved OS was associated with a positive status for pan-ER beta (HR=0.60, 95% CI 0.45-0.80, P=0.0004) and ER beta-2 (HR=0.44, 95% CI 0.31-0.62, P<0.0001). In ERa-positive patients, ER beta 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, ER beta 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 ERa-negative patients. We did not observe an association between ER beta mRNA levels and DFS and OS. Conclusion: In this study, we showed that IHC ER beta status, rather than mRNA levels, is a prognostic factor that is associated with DFS and OS in breast cancer patients. The prognostic value of ER beta may be higher in ERa-negative patients than in ERa-positive patients.