Biomarkers, Trial Design, and Shared Decision Making for CDK4/6 Use in HR Positive Breast Cancer

This segment synthesizes how clinicopathologic features and emerging translational studies inform CDK4/6 therapy selection and how treatment duration differences enter shared decision making. Panelists prioritize nodal status, high Ki-67, and validated genomic assays such as MammaPrint or Oncotype as key inputs when weighing adjuvant CDK4/6 addition, noting that these markers help identify luminal B biology and long term recurrence risk. Age and prior endocrine sensitivity also influence risk tolerance and agent choice in metastatic disease. Ongoing and planned studies with integrated multi omics, frequent circulating tumor DNA monitoring, and resistance profiling aim to define predictive biomarkers, elucidate mechanisms of CDK4/6 resistance, and test biomarker guided combination strategies in early disease. When discussing duration differences between MONARCH E and NATALEE, clinicians frame conversations around absolute versus individualized benefit, monitoring burden, and patient preferences for shorter versus longer therapy, using these considerations to align regimen, toxicity management, and surveillance with patient goals.