558 Background: Accurate prediction of risk of distant recurrence (DR) in HR+, HER2-negative early-stage breast cancer (EBC) is important for optimizing adjuvant therapy decisions, including treatment escalation with CDK4/6 inhibitors (CDK4/6i). Current guidelines recommend consideration of CDK4/6i for node-positive, clinically high-risk EBC, including N1 patients. However, it is not known which patients will benefit, and guideline recommendations suggest that the risks may outweigh benefits for patients with low risk of distant recurrence. Identification of these patients will help prevent over-treatment. RlapsRisk BC (RR) is an AI pathology-based test that integrates features from H p < .001). Estimated 10-year DR-free was 87.5% (95% CI: 83.9-90.4%) for low-risk vs. 65.0% (95% CI: 59.1-70.2%) for high-risk patients. In a multivariable Cox model, the histology-only score remained significant after adjusting for clinicopathologic data: HR=1.6 (95% CI: 1.4-1.9; p < .001). In the N1 subgroup, RR identified 65.7% of patients as low-risk with an estimated 10-year DR-free of 90.6% (95% CI: 86.9-93.4%), compared to 69.8% (95% CI: 62.2-76.2%) for high-risk. Conclusions: RR demonstrates robust prognostic performance in clinically high-risk N+, HR+, HER2-negative EBC patients from the NSABP-28 trial, in which the majority of patients had N1 disease. Our results demonstrate that approximately two-thirds of N1 patients, identified as low-risk by RR, exhibited favorable long-term outcomes with standard chemoendocrine therapies alone. As the clinical landscape shifts toward broader CDK4/6i use, RR could be used to identify N1 patients for whom the benefit of treatment intensification may be minimal.
Rastogi et al. (2026) studied this question.