TY - JOUR
TI - Do type 1 receptor tyrosine kinases inform treatment choice? A
prospectively planned analysis of the TEAM trial
AU - Bartlett, J. M. S.
AU - Brookes, C. L.
AU - Piper, T.
AU - van de Velde, C.
AU - J. H.
AU - Stocken, D.
AU - Lyttle, N.
AU - Hasenburg, A.
AU - Quintayo, M.
AU - A.
AU - Kieback, D. G.
AU - Putter, H.
AU - Markopoulos, C.
AU - Kranenbarg,
AU - E. M-K
AU - Mallon, E. A.
AU - Dirix, L. Y.
AU - Seynaeve, C.
AU - Rea, D.
AU - W.
JO - British Journal of Cancer
PY - 2013
VL - 109
TODO - 9
SP - 2453-2461
PB - Nature Publishing Group
SN - 0007-0920, 1532-1827
TODO - 10.1038/bjc.2013.609
TODO - null
TODO - 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% HER2positive, 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 treatmentby- 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.
ER -