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 α 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 α 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 α specifically phosphorylated at Ser 118 expression to disease-free survival and overall survival was determined. Results: Estrogen receptor α specifically phosphorylated at Ser 118 was limited to estrogen receptor α ligand binding assay-positive tumors and among this subset was expressed in 70 (62%) of these tumors. Estrogen receptor α specifically phosphorylated at Ser 118 expression was more frequently observed in progesterone receptor-positive tumors compared with progesterone receptor-negative tumors (χ 2 test, P = 0.012, n = 113). A significant correlation was also seen between estrogen receptor α 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 α 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 receptor-positive/estrogen receptor α specifically phosphorylated at Ser 118 -positive patients had a significantly longer disease-free survival that progesterone receptor-positive/estrogen receptor α specifically phosphorylated at Ser 118 -negative patients ( P = 0.0041). Conclusions: Our data suggest that estrogen receptor α 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 α specifically phosphorylated at Ser 118 status has the potential to provide a more precise biomarker of responsiveness to endocrine therapy in conjunction with estrogen receptor α and progesterone receptor status.