Do type 1 receptor tyrosine kinases inform treatment choice? A prospectively planned analysis of the TEAM trial

Research output: Contribution to journalArticlepeer-review


  • J. M S Bartlett
  • C. L. Brookes
  • T. Piper
  • C. J H Van De Velde
  • D. Stocken
  • N. Lyttle
  • A. Hasenburg
  • M. A. Quintayo
  • D. G. Kieback
  • H. Putter
  • C. Markopoulos
  • E. M K Kranenbarg
  • E. A. Mallon
  • L. Y. Dirix
  • C. Seynaeve

Colleges, School and Institutes

External organisations

  • Leiden University Medical Center - LUMC
  • Ontario Institute for Cancer Research
  • University Hospital
  • Elblandklinikum
  • Athens University
  • Western Infirmary
  • Oncology Center
  • Erasmus MC
  • University of Edinburgh


Background:Epidermal growth factor receptors contribute to breast cancer relapse during endocrine therapy. Substitution of aromatase inhibitors (AIs) may improve outcomes in HER-positive cancers.Methods:Tissue microarrays were constructed. Quantitative analysis of HER1, HER2, and HER3 was performed. Data were analysed relative to disease-free survival and treatment using outcomes at 2.75 and 6.5 years.Results:Among 4541 eligible samples, 4225 (93%) had complete HER1-3 data. Overall, 5% were HER1-positive, 13% HER2-positive, and 21% HER3-positive; 32% (n=1351) overexpressed at least one HER receptor. In the HER1-3-negative subgroup, the hazard ratio (HR) for upfront exemestane vs tamoxifen at 2.75 years was 0.67 (95% confidence interval (CI), 0.52-0.87), in the HER1-3-positive subgroup, the HR was 1.15 (95% CI, 0.85-1.56). A prospectively planned treatment-by-marker analysis demonstrated a significant interaction between HER1-3 and treatment at 2.75 years (HR=0.58; 95% CI, 0.39-0.87; P=0.008), as confirmed by multivariate regression analysis adjusting for prognostic factors (HR=0.55; 95% CI, 0.36-0.85; P=0.005). This effect was time dependent.Conclusion:In the 2.75 years prior to switching patients initially treated with tamoxifen to exemestane, a significant treatment-by-marker effect exists between AI/tamoxifen treatment and HER1-3 expression, suggesting HER expression could be used to select appropriate endocrine treatment at diagnosis to prevent or delay early relapses.


Original languageEnglish
Pages (from-to)2453-2461
Number of pages9
JournalBritish Journal of Cancer
Issue number9
Publication statusPublished - 29 Oct 2013


  • early breast cancer, exemestane, HER1/EGFR, HER2, HER3, oestrogen receptor, tamoxifen

ASJC Scopus subject areas

Sustainable Development Goals