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Cyclin-dependent kinase (CDK) 4/6 inhibitors have demonstrated significant advances in the treatment of hormone receptor (HR) positive and human epidermal growth factor receptor (HER2) negative advanced breast cancer. While current available data do not support the preferential use of one agent over the other, the dosing and safety monitoring differ and may help in treatment decision making with patients. Multi-disciplinary care teams have key roles in education and supportive care management to optimize the use of these agents and disease response.1,2