title: Activated HER-receptors in predicting outcome of ER-positive breast cancer patients treated with adjuvant endocrine therapy.
abstract: The four human epidermal growth factor receptors (HER1-4) are involved in growth stimulation and may play a role in endocrine resistance. The receptors form dimers, leading to activation by mutual phosphorylation. Our purpose was to explore the role of the activated receptors (pHER1, pHER2, pHER3) in endocrine treated breast cancer in terms of co-expression and association with disease-free survival (DFS) in 1062 patients with ER-positive tumors. Furthermore, HER2 amplification was evaluated. We found positive associations between the phosphorylated receptors. pHER1 and pHER3 were co-expressed with one or two of the other activated receptors in 85% and 89% of tumors, respectively, whereas pHER2 was co-expressed with the other activated receptors in 54% of tumors. Except for HER2, which was associated with poor prognosis, none of the remaining markers were associated with DFS. However, frequent co-expression indicates a role of the other HER-family members in activation of HER2.
authors.affiliation: Department of Pathology, Herlev Hospital, Herlev Ringvej 75, 2730 Herlev, Denmark. mathilde.skaarup.larsen@regionh.dk
authors.forename: Mathilde S
authors.initials: MS
authors.lastname: Larsen
authors.forename: Karsten
authors.initials: K
authors.lastname: Bjerre
authors.forename: Anne E
authors.initials: AE
authors.lastname: Lykkesfeldt
authors.forename: Anita
authors.initials: A
authors.lastname: Giobbie-Hurder
authors.forename: Anne-Vibeke
authors.initials: AV
authors.lastname: Laenkholm
authors.forename: Katrine L
authors.initials: KL
authors.lastname: Henriksen
authors.forename: Bent
authors.initials: B
authors.lastname: Ejlertsen
authors.forename: Birgitte B
authors.initials: BB
authors.lastname: Rasmussen
mesh_terms: D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004311:Double-Blind Method; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D000077289:Letrozole; D008408:Mastectomy; D008875:Middle Aged; D009570:Nitriles / Q000627:therapeutic use*; D010766:Phosphorylation; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D020893:Receptor, ErbB-3 / Q000378:metabolism; D066247:Receptor, ErbB-4; D013629:Tamoxifen / Q000627:therapeutic use*; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D000077289:Letrozole; D009570:Nitriles; D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4; D013629:Tamoxifen; D014230:Triazoles; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C587689:ERBB4 protein, human