title: Analysis of MET genetic aberrations in patients with breast cancer at MD Anderson Phase I unit.
abstract: 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.
authors: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address: dgagliato@gmail.com.
authors: Debora
authors: D
authors: de Melo Gagliato
authors: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX.
authors: Denis L Fontes
authors: DL
authors: Jardim
authors: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX.
authors: Gerald
authors: G
authors: Falchook
authors: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors: Chad
authors: C
authors: Tang
authors: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX.
authors: Ralph
authors: R
authors: Zinner
authors: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX.
authors: Jennifer J
authors: JJ
authors: Wheler
authors: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX.
authors: Filip
authors: F
authors: Janku
authors: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX.
authors: Vivek
authors: V
authors: Subbiah
authors: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX.
authors: Sarina A
authors: SA
authors: Piha-Paul
authors: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX.
authors: Siqing
authors: S
authors: Fu
authors: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors: Kenneth
authors: K
authors: Hess
authors: Department of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors: Sinchita
authors: S
authors: Roy-Chowdhuri
authors: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors: Stacy
authors: S
authors: Moulder
authors: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors: Ana M
authors: AM
authors: Gonzalez-Angulo
authors: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX.
authors: Funda
authors: F
authors: Meric-Bernstam
authors: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX.
authors: David S
authors: DS
authors: Hong
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D018275:Carcinoma, Lobular / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D005260:Female; D005500:Follow-Up Studies; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: MET amplification; MET mutation; Metastatic breast cancer; Personalized therapy; c-MET inhibitors