The rationale to study this combination in HER2 positive breast cancers has also been strengthened by a recent investigation of Miller et al. who demonstrated that inhibition of PI3K and mTOR are required for the growth inhibitory effects of HER2 antagonists in HER2 overexpressing breast cancer and that inhibition of mTOR is an effective therapeutic strategy in TZ resistant breast cancer models [48]. This evidence concerns the gene ERBB2 and breast carcinoma.