cMET and Phospho-cMET Protein Levels in Breast Cancers and Survival Outcomes

PURPOSE: To evaluate cMET (mesenchymal-epithelial transition factor gene) and phospho-cMET (p-cMET) levels in breast cancer subtypes and its impact on survival outcomes. EXPERIMENTAL DESIGN: 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.