C-Met in invasive breast cancer: is there a relationship with the basal-like subtype?

Background: Basal-like (BL) breast cancer is an aggressive form of breast cancer with limited treatment options. Recent work has identified BL breast cancer as a biologically distinct form of triple-negative breast cancer, with a worse outlook. The receptor tyrosine kinase c-Met is a novel therapeutic target associated with reduced survival in breast cancer. Few studies have specifically addressed the association between c-Met and molecular subtype of breast cancer, yet this is a key consideration when selecting patients for clinical trials. The aim of this study is to evaluate c-Met expression in a large cohort of invasive breast cancers and in particular, its correlation with molecular subtype.

Methods: Immunohistochemistry for c-Met was performed and evaluated on 1274 invasive breast cancers using tissue microarray technology. The c-Met scores were correlated with molecular subtype, survival, and other standard clinicopathological prognostic factors.

Results: Multivariate logistic regression showed c-Met was independently associated with BL status (odds ratio=6.44, 95% confidence interval=1.74-23.78, P=.005). There was a positive correlation between c-Met and Her2 (P=.005) and an inverse correlation with tumor size (P<.001). C-Met was an independent poor prognostic factor at Cox regression analysis in all subtypes (hazard ratio=1.85, 95% confidence interval=1.07-3.19, P=.027) and there was a trend toward reduced survival in BL tumors overexpressing c-Met, but this was not significant.

Conclusions: C-Met is independently associated with BL breast cancer. In the future, patients with BL tumors should be included in clinical trials of anti-c-Met therapy.