Although initial attempts to combine CDK4/6 and PI3K inhibitors led to prohibitive toxicity [75], certain combinations have shown promise in PIK3CA mutant breast cancer [76], ultimately leading to the initiation of an ongoing randomized phase 3 trial exploring the benefit of adding inavolisib to the palbociclib/fulvestrant doublet (NCT04191499). This evidence concerns the gene CDK4 and breast cancer.