CDK4/6 inhibitors have been approved for estrogen receptor positive, HER2- metastatic breast cancers with concurrent anti-estrogen therapy and may be effective in the Sheepdog with wild-type RB1. DLG2, Disks Large Homolog 2, encodes a multi-domain scaffold protein in the Hippo signaling pathway that is important for defining epithelial polarity during cell division and loss of function of DLG2 contributes to cell cycle progression and invasion in cancer cells [59]. Here, ESR1 is linked to cancer.