Analysis of potential activation of AKT/PI3K signalling in HCC1954-L cells by the mTOR/IGFIR feedback loop identified by Petricoin et al 2007 [42] demonstrated that treatment with both lapatinib and rapamycin did not increase phosphorylation of either mTOR or IGFIR However, these data suggest that refametinib sensitivity in HER2-positive breast cancer cells could be limited by feedback loop activation, and that the mechanisms underlying these feedback loops may differ between parental HER2-positive breast cancer cells and cells that have acquired resistance to HER2-inhibitors. This evidence concerns the gene PIK3CA and breast carcinoma.