HR+/HER2– early breast cancer carries residual recurrence risk despite endocrine therapy, particularly in node-positive or high-risk genomic subgroups, driving investigation of CDK4/6 inhibitors as adjuvant intensification.

Phase 3 evidence demonstrated that adjuvant CDK4/6 inhibitor plus endocrine therapy significantly improved invasive disease-free survival (iDFS) in high-risk HR+/HER2– early breast cancer, with the greatest absolute benefit in patients with high Ki-67 expression (≥20%). Updated 5-year data confirm durable iDFS and distant relapse-free survival benefits persisting beyond the 2-year treatment period, suggesting a disease-modifying carryover effect. Tolerability, particularly diarrhea, fatigue, and dose modifications, requires proactive management to preserve adherence. Ki-67 testing standardization, patient preference, and multidisciplinary workflow integration remain key implementation considerations.

Medical oncologists, breast surgical oncologists, and pathologists managing high-risk HR+/HER2– early breast cancer will benefit from peer discussion on patient selection, Ki-67 testing, adherence strategies, and the evolving adjuvant CDK4/6 inhibitor evidence base.

How do you integrate Ki-67 expression and nodal burden into adjuvant CDK4/6 inhibitor decision-making in HR+/HER2– early breast cancer? What strategies have you found most effective for managing adherence and tolerability during the adjuvant CDK4/6 inhibitor course?