Defining High-Risk HR+/HER2− Early Breast Cancer for Adjuvant CDK4/6 Therapy

The discussion opens with an overview of the evolving treatment landscape for patients with high-risk HR-positive/HER2-negative early breast cancer, highlighting how adjuvant CDK4/6 inhibitors have expanded treatment options beyond endocrine therapy alone. The faculty review the evidence supporting these agents and discuss how clinical trial eligibility criteria from monarchE and NATALEE inform treatment selection in routine practice. Particular attention is given to assessing recurrence risk using factors such as nodal involvement, tumor size, grade, and other clinicopathologic features while recognizing that many patients do not fit neatly within trial-defined populations. The conversation also addresses the challenges clinicians face when applying study criteria to real-world cases and emphasizes the importance of individualized decision-making. Practical considerations surrounding node-positive and selected node-negative disease are explored as the panel discusses how recurrence risk ultimately guides recommendations for adjuvant CDK4/6 inhibitor therapy.