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

Br J Cancer. 2013 Oct 29;109(9):2453-61. doi: 10.1038/bjc.2013.609. Epub 2013 Oct 3.


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.

Trial registration: NCT00032136 NCT00036270 NCT00279448.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Androstadienes / therapeutic use
  • Aromatase Inhibitors / therapeutic use
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism*
  • Disease-Free Survival
  • ErbB Receptors / metabolism*
  • Female
  • Humans
  • Middle Aged
  • Molecular Sequence Data
  • Prognosis
  • Prospective Studies
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Selective Estrogen Receptor Modulators / therapeutic use
  • Tamoxifen / therapeutic use
  • Tissue Array Analysis


  • Androstadienes
  • Aromatase Inhibitors
  • Biomarkers, Tumor
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Selective Estrogen Receptor Modulators
  • Tamoxifen
  • ErbB Receptors
  • exemestane

Associated data

  • NTR/267