Expression of Estrogen Receptor Beta and Phosphorylation of Estrogen Receptor Alpha Serine 167 Correlate with Progression-Free Survival in Patients with Metastatic Breast Cancer Treated with Aromatase Inhibitors

Aromatase inhibitor (AI) is widely used as an endocrine treatment in postmenopausal patients with hormone receptorpositive breast cancer. To identify useful prognostic factors for patients with metastatic breast cancer treated with AI therapy, we investigated the association between several hormone receptor-related factors and prognosis. The expressions of estrogen receptor-alpha (ER alpha), ER beta, progesterone receptor, the phosphorylation of ER alpha serine 118 (Ser118) and ER alpha Ser167 were examined using immunohistochemical techniques for the primary tumors of 41 patients with metastatic breast cancer who received first-line AI therapy after relapse. To assess the associations of protein expression and phosphorylation levels with progression-free survival (PFS), the levels of each factor were categorized into low and high values at optimal cutoff points. In univariate analysis, high ER alpha expression and high ER alpha Ser167 phosphorylation correlated with longer PFS (p = 0.016 and 0.013, respectively). In multivariate analysis, low ER beta expression and high ER alpha Ser167 phosphorylation correlated with longer PFS (p = 0.031 and 0.004, respectively). Patients with both low ER beta expression and high ER alpha Ser167 phosphorylation had longer PFS than the others (p = 0.0107). These data suggest that the expression of ER beta and phosphorylation of ER alpha Ser167 may be useful prognostic factors in patients with metastatic breast cancer who received first-line AI therapy. Copyright (C) 2010 S. Karger AG, Basel