Analysis of MET Genetic Aberrations in Patients With Breast Cancer at MD Anderson Phase I Unit

作者：Gagliato Debora de Melo^*; Jardim Denis L Fontes; Falchook Gerald; Tang Chad; Zinner Ralph; Wheler Jennifer J; Janku Filip; Subbiah Vivek; Piha Paul Sarina A; Fu Siqing; Hess Kenneth; Roy Chowdhuri Sinchita; Moulder Stacy; Gonzalez Angulo Ana M; Meric Bernstam Funda; Hong David S

来源：Clinical Breast Cancer, 2014, 14(6): 468-474.

DOI：10.1016/j.clbc.2014.06.001

• c-MET inhibitors
• MET amplification
• Metastatic breast cancer
• MET mutation
• Personalized therapy

MET aberrations were associated with adverse tumor pathologic features, such as high grade and hormone receptor negativity in a cohort of breast cancer patients referred to a Phase I program. Additionally, patients with MET aberrations had inferior overall survival from Phase I consult compared with wild-type patients. These findings are quite provocative, identifying a subset of patients at a particularly high risk for worse survival outcomes. %26lt;br%26gt;Background: c-MET is a receptor tyrosine kinase whose phosphorylation activates important proliferation pathways. MET amplification and mutation have been described in various malignancies, including breast cancer (BC), and c-MET overexpression is associated with worse survival outcomes in patients with BC. We describe MET mutation and amplification rates in a BC cohort of patients referred to a Phase I Unit. Methods: We reviewed the electronic medical records of all patients with advanced BC tested for MET amplification, mutation, or both who were referred to the Department of Investigational Cancer Therapeutics at MD Anderson. Results: A total of 107 patients with advanced BC were analyzed for MET mutation/variant (88 patients) or amplification (63 patients). Of these, 49 were tested for both genetic abnormalities. Three of 63 patients (4.7%) demonstrated MET gene amplification by fluorescence in situ hybridization (2 in primary tissue; 1 in metastatic site). MET mutation/variant was detected in 8 of 88 patients (9%). High-grade tumors were characteristic of all patients harboring MET amplification and were present in 7 of 8 (87.5%) of those with MET mutation. Metastatic sites were greater in MET-amplified compared with wild-type Patients (median of 7 vs. 3 sites). Five of 8 patients (62.5%) with MET mutations had triple negative BC compared with 46% in controls. In addition, patients with positive test results for MET aberrations (n = 11) had inferior overall survival (OS) from Phase I consult compared with wild-type patients (n = 37), although this was not statistically significant (median OS = 9 vs. 15 months, P = .43). Conclusions: In this cohort of patients with BC who were referred to our Phase I Department, MET aberrations were associated with higher metastatic burden and high-grade histology. We could not demonstrate differences in survival outcomes because of a small sample size.

• 出版日期2014-12