The combination of mTOR or PI3K inhibitors to CDK4/6 inhibitor therapy have shown encouraging preliminary results in clinical trials, although PI3K inhibitors resulted to be quite toxic and poorly effective and, therefore, they are not yet approved for breast cancer (Hamilton and Infante, 2016; Cortes et al., 2017; Ballinger et al., 2018). This evidence concerns the gene CDK4 and breast cancer.