Enobosarm in combination with CDK4/6 inhibitors has also been shown to be efficacious in the setting of endocrine or CDK4/6 inhibitor-resistant breast cancer models (which retain the expression of AR), suggesting that AR agonism may partially restore sensitivity to CDK4/6 inhibitors, thus positing that this combination may be an effective therapeutic strategy in the second-line treatment of ER+ metastatic breast cancer [16]. Here, ESR1 is linked to breast carcinoma.