title: Expression of activated type I receptor tyrosine kinases in early breast cancer.
abstract: Overexpression of EGFR, HER2 and HER3 are known to be associated with poor outcome in breast cancer. Few studies have examined the clinical impact of activation of these proteins. In the present study, we evaluated EGFR, HER2 and HER3 and the activated (phosphorylated) forms of these proteins in patients with early breast cancer. EGFR, HER2, HER3, pEGFR, pHER2 and pHER3 expression was determined by immunohistochemical analysis of tissue microarrays constructed from tumours within the Edinburgh Breast Conservation Series (BCS). The BCS represents a fully-documented consecutive cohort of 1,812 patients treated by breast conservation surgery in a single institution. Our results demonstrate overexpression of HER2 and pHER2 to be associated with a significant reduction in overall survival (OS) (HR: 1.66, 95 % CI 1.22-2.26, p = 0.001 and HR: 1.57, 95 % CI 1.22-2.03, p = 0.001, respectively) and distant relapse-free survival (DRFS) (HR: 1.63, 95 % CI 1.23-2.18, p = 0.001 and HR: 1.55, 95 % CI 1.23-1.97, p = 0.0002, respectively). Paradoxically, expression of pEGFR was associated with a significantly improved OS (HR: 0.67 95 % CI 0.50-0.91, p = 0.01) and DRFS (HR: 0.73, 95 % CI 0.56-0.96, p = 0.025). Expression of activated EGFR/HER2 provides additional information on ER positive breast cancer patients and suggests alternative treatment for those in this subgroup.
authors.affiliation: Transformative Pathology, Ontario Institute for Cancer Research, MaRS Centre, South Tower, 101 College St, Suite 800, Toronto, ON, M5G 043, Canada.
authors.forename: Melanie
authors.initials: M
authors.lastname: Spears
authors.forename: Hans Christian
authors.initials: HC
authors.lastname: Pederson
authors.forename: Nicola
authors.initials: N
authors.lastname: Lyttle
authors.forename: Claire
authors.initials: C
authors.lastname: Gray
authors.forename: Mary Anne
authors.initials: MA
authors.lastname: Quintayo
authors.forename: Lyndsay
authors.initials: L
authors.lastname: Brogan
authors.forename: Jeremy St
authors.initials: JS
authors.lastname: J Thomas
authors.forename: Gillian R
authors.initials: GR
authors.lastname: Kerr
authors.forename: Wilma J L
authors.initials: WJ
authors.lastname: Jack
authors.forename: Ian H
authors.initials: IH
authors.lastname: Kunkler
authors.forename: David A
authors.initials: DA
authors.lastname: Cameron
authors.forename: Udi
authors.initials: U
authors.lastname: Chetty
authors.forename: John M S
authors.initials: JM
authors.lastname: Bartlett
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D015331:Cohort Studies; D018572:Disease-Free Survival; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D020893:Receptor, ErbB-3 / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D013629:Tamoxifen / Q000627:therapeutic use; D046888:Tissue Array Analysis
chemical_list: D018931:Antineoplastic Agents, Hormonal; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D011960:Receptors, Estrogen; D013629:Tamoxifen; C508053:ERBB2 protein, human