Possible next steps in studies utilizing these genetically engineered mouse models would be to directly test if earlier intervention with tamoxifen could prevent emergence of tamoxifen-resistant hyperplasias and cancers as well as to investigate if adding a therapeutic agent such as a CDK4/6 inhibitor targeting the cyclin D1 signaling pathway [49] might limit development of tamoxifen resistance. This evidence concerns the gene CDK4 and cancer.