TY - JOUR
T1 - Analysis of MET genetic aberrations in patients with breast cancer at MD anderson phase i unit
AU - De Melo Gagliato, Debora
AU - Jardim, Denis L.Fontes
AU - Falchook, Gerald
AU - Tang, Chad
AU - Zinner, Ralph G
AU - Wheler, Jennifer Jane
AU - Janku, Filip
AU - Subbiah, Vivek
AU - Piha-Paul, Sarina A.
AU - Fu, Siqing
AU - Hess, Kenneth R
AU - Roy-Chowdhuri, Sinchita
AU - Moulder, Stacy
AU - Gonzalez-Angulo, Ana M.
AU - Meric-Bernstam, Funda
AU - Hong, David S.
N1 - Publisher Copyright:
© 2014 Elsevier Inc. All rights reserved.
PY - 2014/12/1
Y1 - 2014/12/1
N2 - 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.
AB - 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.
KW - C-MET inhibitors
KW - MET amplification
KW - MET mutation
KW - Metastatic breast cancer
KW - Personalized therapy
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U2 - 10.1016/j.clbc.2014.06.001
DO - 10.1016/j.clbc.2014.06.001
M3 - Article
C2 - 25065564
AN - SCOPUS:84911442494
SN - 1526-8209
VL - 14
SP - 468
EP - 474
JO - Clinical breast cancer
JF - Clinical breast cancer
IS - 6
ER -