Journal article

Increased MET and HGF gene copy numbers are associated with trastuzumab failure in HER2-positive metastatic breast cancer

G Minuti, F Cappuzzo, R Duchnowska, J Jassem, A Fabi, T O'Brien, AD Mendoza, L Landi, W Biernat, B Czartoryska-Arlukowicz, T Jankowski, D Zuziak, J Zok, B Szostakiewicz, M Foszczynska-Kloda, A Tempinska-Szalach, E Rossi, M Varella-Garcia

British Journal of Cancer | NATURE PUBLISHING GROUP | Published : 2012

Abstract

BACKGROUND: To investigate whether copy number gain of MET or hepatocyte growth factor (HGF) affect trastuzumab sensitivity in HER2-positive metastatic breast cancer (MBC). METHODS: We analysed 130 HER2-positive MBC treated with trastuzumab-based therapy. MET and HGF gene copy numbers (GCN) were assessed by fluorescence in situ hybridisation (FISH) in primary breast cancer samples. Receiver operating characteristic analysis was applied to find the best cutoff point for both MET and HGF GCN. RESULTS: MET FISH-positive cases (N=36, mean 3.72) had a significantly higher trastuzumab failure rate (44.4% vs 16.0%; P=0.001) and a significantly shorter time to progression (5.7 vs 9.9 months; HR 1.7..

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