The potential role of estrogen receptor β2 in breast cancer

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.