The involvement of the PI3K/AKT/mTOR pathway in HER2-postive BC is also supported by the resistance to trastuzumab reported in preclinical data in case of PI3K/AKT/mTOR pathway activation, such as PTEN loss (a protein that inhibits the PI3K pathway), PI3KCA mutation (gene coding for a subunit catalyzing AKT protein). Here, PTEN is linked to breast cancer.