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
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..View full abstract
Awarded by Italian Association for Cancer Research (AIRC)
Awarded by National Cancer Institute
Awarded by NATIONAL CANCER INSTITUTE
This work was supported by the Italian Association for Cancer Research (AIRC) (IG9425 to FC and LL), Associazione Oncologia Traslazionale (AOT) (to FC) and the National Cancer Institute (P30-CA46934). We are indebted to the pathology department of Milan University for technical support.