Characteristics and Outcomes of NATALEE- and monarchE-Eligible Early Breast Cancer in Finland: A Regional Real-world Cohort Study

Abstract Background Adjuvant CDK4/6 inhibitors have improved outcomes in hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2–) early breast cancer (eBC) in the NATALEE and monarchE trials. However, real‑world evidence on the proportion of candidates for adjuvant CDK4/6 inhibitors and their outcomes within these trial-defined populations remains limited. Materials and Methods We conducted a retrospective, population‑based cohort study including all patients diagnosed with HR+/HER2– eBC in the Hospital District of Helsinki and Uusimaa, Finland, between January 2014 and June 2023. Patients were classified according to NATALEE and/or monarchE eligibility criteria. Outcomes assessed were invasive disease‑free survival (iDFS), distant disease‑free survival (DDFS), and overall survival (OS). Results Among 8,911 patients with HR+/HER2- eBC and a median follow-up of 5.2 years, 40.4% met the NATALEE eligibility criteria and 15.0% met the monarchE criteria. Eligible patients were younger and had higher‑grade tumors and greater proliferation rate than non-eligible patients. Five‑year outcomes were consistently worse in eligible than ineligible patients (NATALEE: iDFS 82.5% vs. 89.6%, DDFS 88.3% vs. 94.5%, OS 90.9% vs. 95.6%; monarchE: iDFS 76.8% vs. 88.4%, DDFS 82.3% vs. 93.8%, OS 86.8% vs. 94.9%). Metastatic progression occurred three‑ to six‑fold more often in eligible patients. In multivariable models, both NATALEE and monarchE eligibility were associated with distant metastasis, and mortality. Conclusion Real-world outcomes among NATALEE and monarchE-eligible patients are consistent with results from phase III trial comparator arms. Trial‑defined eligibility criteria reliably identify patients with substantially poorer prognosis, supporting risk‑adapted adjuvant strategies and the integration of CDK4/6 inhibitors into clinical practice.