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 î¶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 1.74; P=0.006) than MET FISH-negative cases (N=94, mean <3.72). Hepatocyte growth factor GCN was evaluated in 84 cases (64.6%). Receiver operating characteristic analysis identified 33 HGF FISH-positive patients (mean HGF GCN î¶3.01). HGF FISH-positive status was significantly associated with higher risk of failure (30.3% vs 7.8%; P=0.007) as compared with HGF FISH-negative cases (N=51, mean <3.01). MET and HGF FISH-positive status was highly correlated (P<0.001) and combination of both biomarkers did not increase predictive value of either considered separately. CONCLUSION: High GCNs of MET and HGF associate with an increased risk of trastuzumab-based therapy failure in HER2-positive MBC.
Subject(s)
Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Gene Dosage , Hepatocyte Growth Factor/genetics , Proto-Oncogene Proteins c-met/genetics , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/administration & dosage , Antineoplastic Agents/administration & dosage , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Drug Resistance, Neoplasm , Female , Hepatocyte Growth Factor/metabolism , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Middle Aged , Prognosis , Proto-Oncogene Proteins c-met/metabolism , Receptor, ErbB-2/biosynthesis , Receptor, ErbB-2/metabolism , Retrospective Studies , TrastuzumabABSTRACT
BACKGROUND: Ten patients with breast cancer and a breast cancer susceptibility gene 1 (BRCA1) mutation, who presented with stages I to III breast cancer between December 2006 and 2007, were treated with four cycles of neoadjuvant cisplatin, followed by mastectomy and conventional chemotherapy. METHODS: The excised breast tissue and lymph nodes were examined for the presence of residual disease. RESULTS: Pathologic complete response was observed in nine patients (90%). CONCLUSIONS: Platinum-based chemotherapy appears to be effective in a high proportion of patients with BRCA1-associated breast cancers. Clinical trials are now warranted to determine the optimum treatment for this subgroup of breast cancer patients.
