Phospho-serine-118 estrogen receptor-alpha expression is associated with better disease outcome in women treated with tamoxifen.
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.
Murphy
Leigh C
LC
Manitoba Institute of Cell Biology, Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada. lcmurph@cc.umanitoba.ca
Niu
Yulian
Y
Snell
Linda
L
Watson
Peter
P
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
D018931:Antineoplastic Agents, Hormonal; D047628:Estrogen Receptor alpha; D008024:Ligands; D011980:Receptors, Progesterone; D013629:Tamoxifen; D012694:Serine