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

Abstract

Aromatase inhibitor (AI) is widely used as an endocrine treatment in postmenopausal patients with hormone receptor-positive 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-α (ERα), ERβ, progesterone receptor, the phosphorylation of ERα serine 118 (Ser118) and ERα 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 ERα expression and high ERα Ser167 phosphorylation correlated with longer PFS (p = 0.016 and 0.013, respectively). In multivariate analysis, low ERβ expression and high ERα Ser167 phosphorylation correlated with longer PFS (p = 0.031 and 0.004, respectively). Patients with both low ERβ expression and high ERα Ser167 phosphorylation had longer PFS than the others (p = 0.0107). These data suggest that the expression of ERβ and phosphorylation of ERα Ser167 may be useful prognostic factors in patients with metastatic breast cancer who received first-line AI therapy.