Although our study demonstrates that incorporation of dinaciclib synergizes with palbociclib and fulvestrant to overcome resistance in palbociclib and fulvestrant-resistant BC cells exhibiting high levels of CDK6, p-CDK2 and/or cyclin E1, it remains questionable whether the CDK4/6i should be maintained in the triple combination or switched to another targeted agent that can potentially inhibit the cyclin D-CDK4/6i-Rb cascade more efficiently (i.e., PI3K/mTOR/AKT targeted therapy). This evidence concerns the gene CCNE1 and breast cancer.