ERBB2 and breast cancer: Additionally, a further 5–10% of advanced breast cancers harbour AKT1-activating mutations and 5–10% have inactivating alterations in PTEN. 6, 9, 10, 11 Two agents that inhibit the PI3K/AKT/PTEN pathway have received regulatory approval for ER-positive, HER2-negative advanced breast cancer: the α-isoform-specific PI3K inhibitor, alpelisib, and the mTORC1 inhibitor, everolimus.