Moreover, even though several trials with PI3Ki are ongoing both in HER2+ BC and TNBC, it is necessary to keep on investigating, integrating clinical data with pre-clinical ones, especially after the recent introduction of new agents as standard treatments, such as T-DXd and sacituzumab govitecan, as it is still an open question as to whether PIK3CA mutations may influence their efficacy. This evidence concerns the gene PIK3CA and breast cancer.