Refining risk stratification of patients with early breast cancer eligible for adjuvant abemaciclib or ribociclib

Optimal indications for adjuvant CDK4/6 inhibitors in hormone receptor-positive/HER2-negative early breast cancer remain debated, partly because monarchE and NATALEE trials used different eligibility criteria. Using pooled individual patient-level data from three randomized trials conducted before adjuvant CDK4/6 inhibitors (N = 4,795), we estimated baseline prognosis in eligibility-defined subgroups. Among patients with 1-3 positive lymph nodes (N1; N = 1,646), monarchE high-risk features (tumor size ≥5 cm and/or grade 3) identified a subgroup of patients (N = 493) with worse disease-free survival (HR 1.56; 95% CI 1.27-1.92) and overall survival (HR 1.78; 95% CI 1.34-2.36). Among patients meeting NATALEE-only eligibility criteria (N = 1,346), nodal status (N1 vs N0) did not meaningfully discriminate 7-year outcomes. In simulating prognosis among women treated in the pre-CDK4/6 inhibitor era and meeting varying monarchE and NATALEE eligibility criteria, these data may inform future trial design and clinical practice and stimulate efforts to refine clinical, pathological and molecular criteria for patient selection.