Clinical significance of estrogen receptor β in breast cancer

Abstract

Ever since the estrogen receptor (ER) beta was discovered in 1996, we have been trying to determine its value as a prognostic and/or predictive factor in breast cancer and its potential as a novel target for pharmacological intervention. Recent progress in cellular experiments has shown that ERbeta works as counter partner of ERalpha through inhibition of the transactivating function of ERalpha by heterodimerization, distinct regulation on several specific promoters by ERalpha or ERbeta, and ERbeta-specific regulated genes which are probably related to its anti-proliferative properties. Accumulated data from protein studies in breast cancer tissues indicate that positive expression of ERbeta appears to correlate with a favorable prognosis. Although the number of studies is small, a positive response to tamoxifen treatment is observed in both ERalpha- and ERbeta-positive populations. The significance of ERbeta2/cx, a splicing variant of ERbeta, remains controversial and needs to be analyzed in further studies. We postulate that a combined evaluation of ERbetacx with progesterone receptor may help the stratification of ERalpha-positive breast cancer. Epidemiological studies of hormone replacement therapy and isoflavone (genistein) consumption indicate the possible contribution of ERbeta-specific signaling in breast cancer prevention. A selective estrogen receptor modulator, which works as an antagonist of ERalpha and an agonist of ERbeta, may be a promising chemo-preventive treatment.

3,3′,5-Triiodo-l-thyronine inhibits ductal pancreatic adenocarcinoma proliferation improving the cytotoxic effect of chemotherapy

“…Recent reports have shown that several natural peptides, including thyroid hormones, are able to inhibit cancer cell proliferation , Saji et al 2005, Vesely 2005, Yano et al 2006. In the present study, we have demonstrated that T 3 hormone exposure exerts an anti-proliferative effect on human ductal pancreatic adenocarcinoma cell growth, and that it is able to increase the effect of dFdCyd and DDP acting synergistically with them.…”

Antitumour and biological effects of letrozole and GnRH analogue as primary therapy in premenopausal women with ER and PgR positive locally advanced operable breast cancer

“…The ratio ERa : ER-b within tumour cells has been hypothesised to play a functional role in cell growth (Shaw et al, 2006). Conflicting data have been reported on the role of ER-b either in vitro and in vivo, in that results from preclinical and clinical studies have associated ER-b either positively (protein expression) or negatively (mRNA) with prognosis and response to endocrine treatment (Cappelletti et al, 2004;Saji et al, 2005). The results of our study, showing a significant upregulation of ER-b after treatment irrespective of clinical response, do not help to get further insight into this issue.…”

Is oestrogen receptor- β a predictor of endocrine therapy responsiveness in human breast cancer?

“…In this review, we discuss data concerning ERb expression in human breast cancer in vivo and its relationship to clinical outcome in order to gain insight into the putative function(s) of ERb in human breast cancer. A review has recently been published which also deals with the clinical significance of ERb and its isoforms in breast cancer (Saji et al 2005). The current review builds on this by incorporating additional studies and by focusing specifically on ERb, the relationship between clinical ER assays and endocrine therapy outcome, and the likelihood that ERb in addition to ERa may be a clinically useful biomarker of treatment responsiveness in breast cancer.…”