Everolimus plus exemestane in the phase III BOLERO-2 trial in HR-positive, HER2-negative breast cancer patients pretreated with AI demonstrated a PFS benefit of 6.5 months compared to exemestane alone (HR 0.36, 95% CI 0.27–0.47; p < 0.001), leading to its FDA approval on 20 July 2012 [225]. This evidence concerns the gene ERBB2 and breast cancer.