Outcomes for patients with high-risk ER-positive, HER2-negative early-stage breast cancer: a Danish real-world study

Background: While adjuvant CDK4/6 inhibitors (abemaciclib and ribociclib) have improved invasive disease-free survival (iDFS) in ER-positive, HER2-negative early breast cancer (EBC) in the MonarchE and NATALEE trials, their real-world applicability in Denmark remains unclear. This study evaluates Danish patients meeting comparable high-risk criteria and their outcomes, hypothesizing that a substantial proportion could benefit from additional adjuvant treatment options. Methods: Patients with ER-positive, HER2-negative EBC, diagnosed 2014–2019, who met MonarchE and/or NATALEE eligibility, were included and categorized as intermediate or high risk corresponding to trial definitions. Outcomes were overall survival (OS), iDFS, cumulative incidence of distant recurrence-free survival (DRFS) events and endocrine therapy adherence. Results: Of all new cases of EBC, approximately 31% were included. Of 5,788 patients, 59.1% were intermediate risk and 40.9% high risk. Five-year OS and iDFS were lower in high-risk than intermediate-risk patients (84.5% vs. 91.9% and 76.2% vs. 85.7%, respectively), and cumulative DRFS event rates were higher (18.5% vs. 8.9%). High-risk patients more often received chemotherapy, yet nonchemotherapy subgroups in both risk categories had worse outcomes. Endocrine therapy adherence at 5 years was 77%. Interpretation: A considerable proportion of Danish EBC patients meet high-risk criteria similar to CDK4/6 inhibitor trial populations and experience inferior outcomes despite standard therapy of antihormone treatment +/- chemotherapy. Our real-world data underscore the need for more effective and less toxic adjuvant therapies such as CDK4/6 inhibitors.