title: Phospho-serine-118 estrogen receptor-alpha expression is associated with better disease outcome in women treated with tamoxifen.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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 Ser(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 receptor-positive/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 Ser(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.
authors.affiliation: Manitoba Institute of Cell Biology, Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada. lcmurph@cc.umanitoba.ca
authors.forename: Leigh C
authors.initials: LC
authors.lastname: Murphy
authors.forename: Yulian
authors.initials: Y
authors.lastname: Niu
authors.forename: Linda
authors.initials: L
authors.lastname: Snell
authors.forename: Peter
authors.initials: P
authors.lastname: Watson
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D018572:Disease-Free Survival; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D006801:Humans; D008024:Ligands; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D011980:Receptors, Progesterone / Q000378:metabolism; D012694:Serine / Q000737:chemistry*; D015996:Survival Rate; D013629:Tamoxifen / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D047628:Estrogen Receptor alpha; D008024:Ligands; D011980:Receptors, Progesterone; D013629:Tamoxifen; D012694:Serine