title: Activated ERK1/2 and phosphorylated oestrogen receptor alpha are associated with improved breast cancer survival in women treated with tamoxifen.
abstract: The aim of this study was to investigate the expression of activated (phosphorylated) ERK1/2, oestrogen receptor alpha phosphorylated at S118 (ERalphaS118), and HER2 in primary breast cancer, and to make correlations with the outcome of tamoxifen therapy. We performed immunohistochemical analysis to determine the expression of HER2, ERalphaS118, and activated ERK1/2 in tumours obtained from 279 women with primary breast cancer. HER2 status was also estimated by fluorescence in situ hybridisation. We identified 108 women with ERalpha-positive tumours who had received adjuvant tamoxifen. Activated ERK1/2 (pERK1/2) and ERalphaS118 were found to be associated with each other and with other factors correlated with good prognosis. HER2 was inversely associated with pERK1/2. Positive staining for pERK1/2 (particularly intense staining) indicated better relapse-free survival (P=0.05) and a trend towards better breast cancer-corrected survival in women treated with tamoxifen. To conclude, this study shows that activated ERK1/2 and ERalphaS118 are associated with improved survival. The poorer outcome in HER2-positive women who receive adjuvant tamoxifen cannot be explained by the crosstalk between HER2 and ERalphaS118 via activated ERK1/2 alone.
authors.affiliation: Department of Oncology and Pathology, Karolinska Institute and University Hospital, CCK R8:03, SE-171 76 Stockholm, Sweden.
authors.forename: Jenny
authors.initials: J
authors.lastname: Bergqvist
authors.forename: Goran
authors.initials: G
authors.lastname: Elmberger
authors.forename: John
authors.initials: J
authors.lastname: Ohd
authors.forename: Barbro
authors.initials: B
authors.lastname: Linderholm
authors.forename: Judith
authors.initials: J
authors.lastname: Bjohle
authors.forename: Henrik
authors.initials: H
authors.lastname: Hellborg
authors.forename: Hans
authors.initials: H
authors.lastname: Nordgren
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Borg
authors.forename: Lambert
authors.initials: L
authors.lastname: Skoog
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergh
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010766:Phosphorylation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D016019:Survival Analysis; D013629:Tamoxifen / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D047628:Estrogen Receptor alpha; D048052:Mitogen-Activated Protein Kinase 3; D018719:Erb-b2 Receptor Tyrosine Kinases; D013629:Tamoxifen