Phospho-serine-118 estrogen receptor-α expression is associated with better disease outcome in women treated with tamoxifen

Purpose: The purpose of this research was to determine whether estrogen receptor alpha specifically phosphorylated at Ser(118) is associated with clinical outcome in primary breast tumors from estrogen receptor-positive and node-negative breast cancer patients. Experimental Design: Estrogen receptor alpha specifically phosphorylated at Ser(118). was determined by immunohistochemistry in 117 primary breast tumors from node-negative patients who were subsequently treated with adjuvant tamoxifen. The relationship of estrogen receptor alpha specifically phosphorylated at Ser(118) expression to disease-free survival and overall survival was determined. Results: Estrogen receptor alpha specifically phosphorylated at Ser(118) was limited to estrogen receptor alpha ligand binding assay-positive tumors and among this subset was expressed in 70 (62%) of these tumors. Estrogen receptor alpha specifically phosphorylated at Seri(118) expression was more frequently observed in progesterone receptor-positive tumors compared with progesterone receptor-negative tumors (chi(2) test, p = 0.012, n = 113). A significant correlation was also seen between estrogen receptor alpha specifically phosphorylated at Ser(118) and progesterone receptor levels (Spearman r = 0.236, P = 0.0118, n = 113). Kaplan-Meier outcome analysis showed that patients whose primary tumors expressed estrogen receptor alpha specifically phosphorylated at Ser(118) had a longer disease-free survival (P = 0.0018, n = 113) and a trend toward better overall survival, but this was not statistically significant. Among the subset of progesterone receptor-positive tumors, progesterone receptorpositive/estrogen receptor alpha specifically phosphorylated at Ser(118)-positive patients had a significantly longer disease-free survival that progesterone receptor-positive/estrogen receptor alpha specifically phosphorylated at Ser(118)-negative patients (P = 0.0041). Conclusions: Our data suggest that estrogen receptor alpha specifically phosphorylated at Ser(118) is a marker of a functional, intact ligand-dependent estrogen receptor signaling pathway in breast cancer and that estrogen receptor alpha specifically phosphorylated at Seri(118) status has the potential to provide a more precise biomarker of responsiveness to endocrine therapy in conjunction with estrogen receptor alpha and progesterone receptor status.