title: cMET and phospho-cMET protein levels in breast cancers and survival outcomes.
abstract: OBJECTIVE
  To evaluate cMET (mesenchymal-epithelial transition factor gene) and phospho-cMET (p-cMET) levels in breast cancer subtypes and its impact on survival outcomes.
  
  
  METHODS
  We measured protein levels of cMET and p-cMET in 257 breast cancers using reverse phase protein array. Regression tree method and Martingale residual plots were applied to find best cutoff point for high and low levels. Kaplan-Meier survival curves were used to estimate relapse-free (RFS) and overall (OS) survival. Cox proportional hazards models were fit to determine associations of cMET/p-cMET with outcomes after adjustment for other characteristics.
  
  
  RESULTS
  Median age was 51 years. There were 140 (54.5%) hormone receptor (HR) positive, 53 (20.6%) HER2 positive, and 64 (24.9%) triple-negative tumors. Using selected cutoffs, 181 (70.4%) and 123 (47.9%) cancers had high levels of cMET and p-cMET, respectively. There were no significant differences in mean expression of cMET (P < 0.128) and p-cMET (P < 0.088) by breast cancer subtype. Dichotomized cMET and p-cMET level was a significant prognostic factor for RFS [HR: 2.44, 95% confidence interval (CI): 1.34-4.44, P = 0.003 and HR: 1.64, 95% CI: 1.04-2.60, P = 0.033] and OS (HR: 3.18, 95% CI: 1.43-7.11, P = 0.003 and HR: 1.92, 95% CI: 1.08-3.44, P = 0.025). Within breast cancer subtypes, high cMET levels were associated with worse RFS (P = 0.014) and OS (P = 0.006) in HR-positive tumors, and high p-cMET levels were associated with worse RFS (P = 0.019) and OS (P = 0.014) in HER2-positive breast cancers. In multivariable analysis, patients with high cMET had a significantly higher risk of recurrence (HR: 2.06, 95% CI: 1.08-3.94, P = 0.028) and death (HR: 2.81, 95% CI: 1.19-6.64, P = 0.019). High p-cMET level was associated with higher risk of recurrence (HR: 1.79, 95% CI: 1.08-2.95.77, P = 0.020).
  
  
  CONCLUSIONS
  High levels of cMET and p-cMET were seen in all breast cancer subtypes and correlated with poor prognosis.
authors.affiliation: Department of Hematology/Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Kanwal P
authors.initials: KP
authors.lastname: Raghav
authors.forename: Wenting
authors.initials: W
authors.lastname: Wang
authors.forename: Shuying
authors.initials: S
authors.lastname: Liu
authors.forename: Mariana
authors.initials: M
authors.lastname: Chavez-MacGregor
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Meng
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Mills
authors.forename: Funda
authors.initials: F
authors.lastname: Meric-Bernstam
authors.forename: George R
authors.initials: GR
authors.lastname: Blumenschein
authors.forename: Ana M
authors.initials: AM
authors.lastname: Gonzalez-Angulo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D010766:Phosphorylation; D011379:Prognosis; D016016:Proportional Hazards Models; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019859:Proto-Oncogene Proteins c-met; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone