Clinical significance of estrogen receptor β in breast cancer

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 ER beta works as counter partner of ER alpha through inhibition of the transactivating function of ERa by heterodimerization, distinct regulation on several specific promoters by ER alpha or ER beta, and ER beta-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 ER beta appears to correlate with a favorable prognosis. Although the number of studies is small, a positive response to tamoxifen treatment is observed in both ER alpha- and ER beta-positive populations. The significance of ER beta 2/cx, a splicing variant of ER beta, remains controversial and needs to be analyzed in further studies. We postulate that a combined evaluation of ER beta cx with progesterone receptor may help the stratification of ER alpha-positive breast cancer. Epidemiological studies of hormone replacement therapy and isoflavone (genistein) consumption indicate the possible contribution of ER beta-specific signaling in breast cancer prevention. A selective estrogen receptor modulator, which works as an antagonist of ERa and an agonist of ER beta, may be a promising chemo-preventive treatment.