Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Tan W

PROVIDER: S-EPMC4891126 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Publications

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

Tan Weige W Li Qian Q Chen Kai K Su Fengxi F Song Erwei E Gong Chang C

Oncotarget 20160301 9

<h4>Background</h4>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.<h4>Method</h4>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 ...[more]

PMID: 26863572

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Project description:ImportanceEstrogen receptor-positive (ER+) tumors of the breast are generally highly responsive to endocrine treatment. Although endocrine therapy is the mainstay of adjuvant treatment for ER+ breast cancer, the role of endocrine therapy in the neoadjuvant setting is unclear.ObjectiveTo evaluate the effect of neoadjuvant endocrine therapy (NET) on the response rate and the rate of breast conservation surgery (BCS) for ER+ breast cancer.Data sourcesBased on PRISMA guidelines, a librarian-led search of PubMed and Ovid MEDLINE was performed to identify eligible trials published from inception to May 15, 2015. The search was performed in May 2015.Study selectionInclusion criteria were prospective, randomized, neoadjuvant clinical trials that reported response rates with at least 1 arm incorporating NET (n = 20). Two authors independently analyzed the studies for inclusion.Data extraction and synthesisPooled odds ratios (ORs), 95% CIs, and P values were estimated for end points using the fixed- and random-effects statistical model.ResultsThe analysis included 20 studies with 3490 unique patients. Compared with combination chemotherapy, NET as monotherapy with aromatase inhibitors had a similar clinical response rate (OR, 1.08; 95% CI, 0.50-2.35; P = .85; n = 378), radiological response rate (OR, 1.38; 95% CI, 0.92-2.07; P = .12; n = 378), and BCS rate (OR, 0.65; 95% CI, 0.41-1.03; P = .07; n = 334) but with lower toxicity. Aromatase inhibitors were associated with a significantly higher clinical response rate (OR, 1.69; 95% CI, 1.36-2.10; P < .001; n = 1352), radiological response rate (OR, 1.49; 95% CI, 1.18-1.89; P < .001; n = 1418), and BCS rate (OR, 1.62; 95% CI, 1.24-2.12; P < .001; n = 918) compared with tamoxifen. Dual combination therapy with growth factor pathway inhibitors was associated with a higher radiological response rate (OR, 1.59; 95% CI, 1.04-2.43; P = .03; n = 355), but not clinical response rate (OR, 0.76; 95% CI, 0.54-1.07; P = .11; n = 537), compared with endocrine monotherapy. The incidence of pathologic complete response was low (<10%).Conclusions and relevanceNeoadjuvant endocrine therapy, even as monotherapy, is associated with similar response rates as neoadjuvant combination chemotherapy but with significantly lower toxicity, suggesting that NET needs to be reconsidered as a potential option in the appropriate setting. Additional research is needed to develop rational NET combinations and predictive biomarkers to personalize the optimal neoadjuvant strategy for ER+ breast cancer.

Project description:BackgroundPublished studies have investigated the prognostic roles of estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) in gastroesophageal cancer patients with the controversial results. The aim of the study was to systematically evaluate the impacts of ERα and ERβ on the overall survival (OS) in patients.MethodRelevant eligible studies were extracted from PubMed, Embase, Web of Science, CNKI and Wanfang databases (from the start date to November 2018) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. HR (hazard ratio) with 95% confidence intervals (CIs) were used to assess the prognostic values of ERα and ERβ for OS in patients.ResultsHigh ERα expression was associated with poor OS (HR = 1.58, 95% CI = 1.29-1.94, P < .001) and ERβ with better OS (HR = 0.56, 95% CI = 0.37-0.83, P = .004) in gastroesophageal cancer. Furthermore, unfavorable OS was found in Chinese gastroesophageal patients with higher ERα expression (HR = 1.57, 95% CI = 1.25-1.96, P < .001) and better OS with higher ERβ expression (HR = 0.51, 95% CI = 0.31-0.83, P < .01) in our subgroup analysis. Meanwhile, worse OS was found in esophageal squamous cell carcinoma (ESCC) patients with high ERα expression (HR = 1.74, 95% CI = 1.33-2.26, P < .001), and favorable OS in ESCC with ERβ overexpression (HR = 0.40, 95% CI = 0.31-0.52, P < .001). Besides, high ERα expression was associated with lower tumor differentiation in ESCC (OR = 1.64; 95% CI = 1.02-2.64, P = .04) and ERβ was linked with better tumor differentiation in gastric adenocarcinoma (GCA) (OR = 0.49; 95% CI = 0.26-0.94, P = .03).ConclusionsERα and ERβ might serve as potential prognostic biomarkers for gastroesophageal cancer patients. ERα overexpression predicted poor OS and lower tumor differentiation, and ERβ suggested favorable OS and better tumor differentiation. Further related studies should be performed to test these results.

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Project description:BackgroundIn hormone receptor-positive (HoR+) breast cancer (BC), gene expression analysis identifies luminal A (LumA), luminal B (LumB), human epidermal growth factor receptor 2 (HER2)-enriched (HER2-E), basal-like (BL) intrinsic subtypes and a normal-like group. This classification has an established prognostic value in early-stage HoR+ BC. Here, we carried out a trial-level meta-analysis to determine the prognostic ability of subtypes in metastatic BC (MBC).Materials and methodsWe systematically reviewed all the available prospective phase II/III trials in HoR+ MBC where subtype was assessed. The primary endpoint was progression-free survival (PFS)/time to progression (TTP) of the LumA subtype compared to non-LumA. Secondary endpoints were PFS/TTP of each individual subtype, according to treatment, menopausal and HER2 status and overall survival (OS). The random-effect model was applied, and heterogeneity assessed through Cochran's Q and I2. Threshold for significance was set at P < 0.05. The study was registered in PROSPERO (ID: CRD42021255769).ResultsSeven studies were included (2536 patients). Non-LumA represented 55.2% and was associated with worse PFS/TTP than LumA [hazard ratio (HR) 1.77, P < 0.001, I2 = 61%], independently of clinical HER2 status [Psubgroup difference (Psub) = 0.16], systemic treatment (Psub = 0.96) and menopausal status (Psub = 0.12). Non-LumA tumors also showed worse OS (HR 2.00, P < 0.001, I2 = 65%), with significantly different outcomes for LumB (PFS/TTP HR 1.46; OS HR 1.41), HER2-E (PFS/TTP HR 2.39; OS HR 2.08) and BL (PFS/TTP HR 2.67; OS HR 3.26), separately (PFS/TTP Psub = 0.01; OS Psub = 0.005). Sensitivity analyses supported the main result. No publication bias was observed.ConclusionsIn HoR+ MBC, non-LumA disease is associated with poorer PFS/TTP and OS than LumA, independently of HER2, treatment and menopausal status. Future trials in HoR+ MBC should consider this clinically relevant biological classification.

Dataset Information

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

Background

Method

Results

Conclusion

Publications

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

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