On the other hand, the combined analysis of BOLERO1 and 3 showed a significant PFS benefit in patients with HER2 positive advanced BC having tumors with with PIK3CA mutations, PTEN loss or hyperactive PI3K pathway (PIK3CA mutations and/or PTEN loss and/or AKT1 mutation) treated with everolimus in combination with trastuzumab, plus either paclitaxel or vinorelbine. Here, PIK3CD is linked to breast cancer.