Predictive value of angiogenesis-related gene profiling in patients with HER2-negative metastatic breast cancer treated with bevacizumab and weekly paclitaxel

Bevacizumab plus weekly paclitaxel improves progression-free survival (PFS) in HER2-negative metastatic breast cancer (mBC), but its use has been questioned due to the absence of a predictive biomarker, lack of benefit in overall survival (OS) and increased toxicity. We examined the baseline tumor angiogenic-related gene expression of 60 patients with mBC with the aim of finding a signature that predicts benefit from this drug. Multivariate analysis by Lasso-penalized Cox regression generated two predictive models: one, named G-model, including 11 genes, and the other one, named GCmodel, including 13 genes plus 5 clinical covariates. Both models identified patients with improved PFS (HR (Hazard Ratio) 2.57 and 4.04, respectively) and OS (HR 3.29 and 3.43, respectively). The G-model distinguished low and high risk patients in the first 6 months, whereas the GC-model maintained significance over time ; This work was supported by a grant from the Independent Clinical Research Program (EC10-342), Independent Clinical Research Program (EC10-342), ISCIII (Instituto de Salud Carlos III), Spanish Ministry of Health, and funded also from Roche Farma S.A.U.