Real-world eligibility for adjuvant CDK4/6 therapy in HR+/HER2− early breast cancer: A comparative analysis of monarchE and NATALEE criteria from a single-institution cohort.

Abstract

e12532 Background: Adjuvant CDK4/6 inhibitors benefit selected HR+/HER2− early breast cancer (EBC), yet monarchE (high-risk node-positive) and NATALEE (broader stage II–III, including high-risk N0) define eligibility differently. Real-world applicability across treatment settings is unclear. Methods: Retrospective study of consecutive stage I–III HR+/HER2−/low EBC treated at KFMC (Jan-2021–Dec-2023). Exclusions: HER2-positive, TNBC, metastatic at diagnosis, or missing key variables. For neoadjuvant cases, clinical T/N were used; for upfront surgery, pathologic T/N. Strict NATALEE rules were applied (N+, or N0 with T4/T3 or T2 plus G3 or Ki-67≥20% or RS≥26). Outcomes were descriptive: overall eligibility, by setting (neoadjuvant vs upfront), overlap (Both, NATALEE-only, monarchE-only), monarchE Cohorts 1/2, and NATALEE-only composition (N+ vs high-risk N0 and N0 subgroups). Results: Among 418 patients (neoadjuvant 253; upfront 165), overall eligibility was NATALEE 317 (75.8%) vs monarchE 196 (46.9%). By setting, eligibility was higher neoadjuvantly(NATALEE 93.7%, monarchE 64.0%) than upfront (48.5% and 20.6%, respectively). Overlap showed Both 196 (46.9%), NATALEE-only 121 (28.9%), monarchE-only 0, and Neither 101 (24.2%)—indicating monarchE is fully nested within NATALEE under strict rules. monarchE composition: Cohort 1: 162 (38.8%) vs Cohort 2: 34 (8.1%); within Cohort 1, N1 + (T≥3 or G3) 116 (71.6%) and N2–3 46 (28.4%). Within NATALEE-only (n = 121): N1 low-risk: 70 (57.9%) and high-risk N0: 51 (42.1%). High-risk N0 subgroups (n = 51): T4N0 6 (11.8%), T3N0 17 (33.3%), T2N0 G3 10 (19.6%), T2N0 G2+risk 18 (35.3%). Conclusions: In this real-world cohort, three-quarters of HR+/HER2− EBC would qualify for adjuvant CDK4/6 therapy by NATALEE, compared with about half by monarchE. The added candidates are primarily stage II high-risk N0 and N1 with lower-risk features, with eligibility particularly high in the neoadjuvantsetting. These data support broader implementation of adjuvant CDK4/6 therapy.