Expression of activated type I receptor tyrosine kinases in early breast cancer

Melanie Spears, Hans Christian Pederson, Nicola Lyttle, Claire Gray, Mary Anne Quintayo, Lyndsay Brogan, Jeremy Thomas, Gillian R Kerr, Wilma J L Jack, Ian H Kunkler, David A Cameron, Udi Chetty, John M S Bartlett

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)701-8
Number of pages8
JournalBreast cancer research and treatment
Volume134
Issue number2
DOIs
Publication statusPublished - Jul 2012

Keywords

  • Antineoplastic Agents, Hormonal
  • Breast Neoplasms
  • Cohort Studies
  • Disease-Free Survival
  • Enzyme Activation
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Receptor, Epidermal Growth Factor
  • Receptor, erbB-2
  • Receptor, erbB-3
  • Receptors, Estrogen
  • Tamoxifen
  • Tissue Array Analysis

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