Short course of EGF receptor tyrosine kinase inhibitor erlotinib (OSI-774) reduces tumor cell proliferation and active MAP kinase in situ in untreated operable breast cancers: A strategy for patient selection into phase II trials with signaling inhibitors
2005
3008 Background: EGFR TKIs may be active only in a subpopulation of breast cancer patients (pts) but currently there are no known predictors of response. This study was designed: 1) to determine the cellular activity of erlotinib (Tarceva) against breast tumors, and 2) to identify a profile suggestive of EGFR dependence. Methods: Newly diagnosed pts are treated with 150mg/day erlotinib for 7–14 days until surgery. The activity of the drug is measured by changes in tumor cell proliferation [by Ki67 immunohistochemistry (IHC)] and apoptosis (by TUNEL) in the initial versus surgical tumor samples. Two methods are used to identify surrogate markers of response: 1) IHC for total EGFR, P-EGFR, HER2, P-HER2, Akt, P-Akt, MAPK, P-MAPK; and 2) protein profiling of whole tissue frozen sections using matrix-assisted laser desorption/ionization mass spectrometry. Results: Overall, treatment was well tolerated with no delays in surgery. Two pts stopped treatment due to grade 2 skin rash. 5/14 pts exhibited a ≥75% inhib...
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