Recurrence risk in HR-positive/HER2-negative early breast cancer: real-world US electronic health records study

The NATALEE and monarchE trials showed significant invasive disease-free survival benefits with the addition of a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) to endocrine therapy (ET) in patients with hormone receptor-positive, HER2-negative (HR+/HER2-) early breast cancer (EBC). This study evaluates outcomes in real-world patients prior to widespread availability of adjuvant CDK4/6is, depending on nodal status, including N0 disease with and without high-risk features.

Anonymized data from the Flatiron Health US electronic health record database (2011 to 2023) were analyzed. Adults with American Joint Committee on Cancer anatomic stage I-III HR+/HER2- EBC who underwent surgery and adjuvant ET were included. Overall and distant recurrence and all-cause mortality risks were assessed descriptively across nodal subgroups using Cox proportional hazards models. Recurrence-free survival, distant recurrence-free survival (DRFS), and overall survival were evaluated using Kaplan-Meier methods in the NATALEE- and monarchE-eligible populations.

Among 7481 analyzed patients, 5387 (72.0%) had N0 disease, including 604 (11.2%) with high-risk features and 4783 (88.8%) without. Additionally, 1626 (21.7%) had N1 and 468 (6.3%) had N2-N3 disease. At a potential median follow-up of 78.0 months, the N0 high-risk subgroup showed overall and distant recurrence and mortality risks similar to those in the N1 subgroup. Overall, 2534 patients (33.9%) were NATALEE-eligible, and 1157 (15.5%) were monarchE-eligible. Both populations showed relatively high 5-year distant recurrence rates (DRFS, 83.1% and 74.6%, respectively).

This contemporary real-world analysis highlights a meaningful recurrence risk in the broader HR+/HER2- EBC population, irrespective of nodal status, and emphasizes the need for effective treatment strategies.