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

Abstract

BackgroundThe 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.MethodWe 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.ResultsIn 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.ConclusionIn 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.

Expression of oxysterol pathway genes in oestrogen‐positive breast carcinomas

“…A positive correlation of ESR1 with age, in addition to the higher ESR1 expression in postmenopausal patients observed in this study both reflect the current view that the prognosis of the patients with ER+ breast cancer should be distinguished by the menopausal status …”

“…epigenetic events such as miRNA expression or protein stabilization).In summary, the present study demonstrates that the downregulation of certain efflux pumps in the tumours of patients with high grade (ABCA9/10) or with poor DFS (ABCG2) has prognostic importance for ER+ breast carcinomas, similar to what was recently demonstrated in patients with ovarian carcinoma 35. A positive correlation of ESR1 with age, in addition to the higher ESR1 expression in postmenopausal patients observed in this study both reflect the current view that the prognosis of the patients with ER+ breast cancer should be distinguished by the menopausal status 36.…”

Circulating 27-hydroxycholesterol and breast cancer tissue expression of CYP27A1, CYP7B1, LXR-β, and ERβ: results from the EPIC-Heidelberg cohort

“…27HC causes conformational change in both the ERα and ERβ [2], and ERβ is known to be expressed in both ERα-positive and ERα-negative tumors [16] as observed in the current study (16.5% of ERβ-positive tumors were ERα/PR-negative). A higher proportion of ERβ-positive tumors were Bcl-2-low; prior studies have evaluted associations between tumor hormone receptor status and Bcl-2 expression, and expression of ERβ or Bcl-2 as prognostic markers [28][29][30][31][32]. The lack of association between other breast cancer characteristics observed in the current study is in line with previous studies [33,34], though an association between ERβ expression and lower-tumor grade has been reported, as have significant associations between ERβ and ERα, between ERβ and PR, and between ERβ and HER2 expression (all p < 0.01) [16].…”

Characteristics and survival of patients with metachronous or synchronous double primary malignancies: breast and thyroid cancer

“…In accordance with our result, some previous studies have also suggested for the role of hormone receptors in the molecular pathogenesis of TC. Sex steroid receptors were found in human thyroid tissue, several TC cell lines, and ER levels were significantly higher in TC compared with normal thyroid tissue [17–19], which have shown the possibility that ER or PR signaling might represent common etiological factors in the development of TC and BC. Other studies have shown that estrogen could up-regulate the expression of cell cycle-related genes and proto-oncogene in thyroid cells, which were likely to contribute to the development of TC [20].…”