MTOR and breast cancer: Furthermore, data from BOLERO-3 and the randomized phase III BOLERO-1, which evaluated the use of everolimus as the first line in HER2 advanced BC (NCT00876395), showed that everolimus addition is especially effective in patients harboring PIK3CA mutations, loss of PTEN, or hyperactivation of the PI3K-AKT-mTOR pathway, supporting the relevance of including the status of these markers in BC diagnosis [138].