The potential role of estrogen receptor β2 in breast cancer

Abstract

Endocrine therapy is provided to all patients with estrogen receptor (ER)-positive breast cancer, but only a subset of them derives clinical benefit. The discovery of ERβ and its five isoforms added another layer of complexity in the regulation of estrogen activity in breast cancer cells. Two large retrospective studies showed conflicting results with regard to the prognostic value of the different ERβ isoforms in patients treated with tamoxifen in an adjuvant setting. This study tested the hypothesis that ERβ1 and, or ERβ2 are correlated with clinical outcome. We identified patients with breast cancer who had undergone surgery at Bucheon St. Mary's Hospital, the Catholic University of Korea, between January 2004 and March 2006. We evaluated 101 consecutive cases for ERβ1 and ERβ2 expression using immunohistochemical staining and obtained other clinicopathology by reviewing medical records. ERβ1 was expressed in 81.2% (79 of 97) and ERβ2 was expressed in 50.5% (51 of 101) of primary breast cancer tissues. Disease-free survival (DFS) and overall survival (OS) of patients with cancers expressing ERβ2 was significantly worse. Moreover, in subgroup analysis according to the tamoxifen treatment, ERβ2 expression was significantly associated with shorter DFS of tamoxifen-treated patients. This study indicates that breast cancer with ERβ2 expression was associated with worse DFS and OS, especially in tamoxifen treated patients. Our results suggest a role for ERβ2 as an independent prognostic marker and might serve as a new therapeutic target.

High Estrogen Receptor β Expression Is Prognostic among Adjuvant Chemotherapy–Treated Patients—Results from a Population-Based Breast Cancer Cohort

“…In the cohort presented by Nakopoulou and colleagues, in which patients received adjuvant chemotherapy and/or endocrine therapy, results were similar to our findings (34). As many of the clinical studies were observational studies and patients often received both chemotherapy and endocrine therapy (35,36), it is somewhat surprising that associations between ERb and chemotherapy have been rarely discussed (7,24). The main finding in this study was the impact of ERb1 75 expression on prognosis among patients who received adjuvant chemotherapy, some of whom also received tamoxifen and/or AIs.…”

“…Also, scoring systems based on combinations of fraction and intensity have been commonly applied (16,33,(46)(47)(48). Higher cutoffs, such as >20% (12,46,49,50) or higher (33,34,36), have also been applied. One highly cited study applied cutoffs for ERb1 þ that resulted in highly skewed distributions; >95% of the patients had ERb1 þ tumors, and although there was a tendency toward a beneficial effect, it was reported as a null finding (46).…”

“…ERb positivity has also been defined by moderate or stronger intensity, thereby excluding the weakly stained cases (12,36,49). Some previous studies have applied cutoffs that ultimately suggested significant prognostic effects on outcome, yet which displayed few, if any, associations with established clinicopathologic characteristics (12,34,36,49), whereas others reported only associations between ERb1 þ and established markers (32).…”

Role of 17β-Estradiol on Cell Proliferation and Mitochondrial Fitness in Glioblastoma Cells

“…e ERβ2 isoform is increased in chronic lymphatic leukemia, prostate cancer, non-small-cell lung cancer, breast cancer, and ovarian cancer [35]. e worsening disease-free survival and overall survival of patients were correlated with ERβ2 expression in patients treated with tamoxifen [36]. Moreover, ERβ2 is involved also in the metastasis of prostate cancer [37].…”

Characteristics, behaviour and role of biomarkers in metastatic triple-negative breast cancer

“…Nonetheless, some studies have demonstrated ERβ positivity to be correlated with a more aggressive clinical outcome15 and with the proliferation marker, Ki-67 43–45. ERβ has also been identified as a novel activator of wild-type p53-dependent transcription, which leads to poorer survival of luminal breast cancer cells 42 46–50…”