Clinical significance of estrogen receptor β in breast cancer

Ever since the estrogen receptor (ER) β 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 ERβ works as counter partner of ERα through inhibition of the transactivating function of ERα by heterodimerization, distinct regulation on several specific promoters by ERα or ERβ, and ERβ-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 ERβ appears to correlate with a favorable prognosis. Although the number of studies is small, a positive response to tamoxifen treatment is observed in both ERα- and ERβ-positive populations. The significance of ERβ2/cx, a splicing variant of ERβ, remains controversial and needs to be analyzed in further studies. We postulate that a combined evaluation of ERβcx with progesterone receptor may help the stratification of ERα-positive breast cancer. Epidemiological studies of hormone replacement therapy and isoflavone (genistein) consumption indicate the possible contribution of ERβ-specific signaling in breast cancer prevention. A selective estrogen receptor modulator, which works as an antagonist of ERα and an agonist of ERβ, may be a promising chemo-preventive treatment.