PI3k/AKT/mTOR inhibitors (everolimus and temsirolimus); other mTOR inhibitors; PI3K and Akt inhibitors alone or in combination; PI3K alpha-specific BYL719 CDK4/6 inhibitors may sensitize PIK3CA mutant breast cancer to PI3K inhibitors; combined HER2+ PI3K pathways may be necessary in tumors with ERBB2 amplification and PIK3CA mutation. This evidence concerns the gene CDK4 and breast cancer.