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.
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.
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.
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. Cancer 2014;120:163–171. © 2013 American Cancer Society.