Please visit answersincme.com/GTJ860 to participate, download slides and supporting materials, complete the post test, and obtain credit. In this activity, an expert in breast cancer discusses endocrine receptor (ER)–positive, human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer. Upon completion of this activity, participants should be better able to: Review how the evolving concept of ER sensitivity is relevant to therapeutic decision-making in patients with ER-positive, HER2-negative advanced breast cancer; Describe the clinical profiles of approved and emerging therapeutic options for ER-positive, HER2-negative advanced breast cancer post–cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor use; Identify clinical strategies to optimize the integration of mutational testing into practice for ER-positive, HER2-negative advanced breast cancer; and Outline a personalized approach to therapeutic decision-making to enhance real-world outcomes in ER-positive, HER2-negative advanced breast cancer after initial CDK4/6 inhibitor therapy.