Spotlight Medical has announced the publication of a peer-reviewed study in the Journal of Clinical Oncology, validating a novel AI-powered pathology assay that identifies a biologically low-risk subgroup among patients clinically classified as high-risk for early-stage ER-positive, HER2-negative breast cancer. The findings could transform treatment decisions for tens of thousands of women annually, potentially sparing up to 30,000 from unnecessary treatment intensification. The assay, developed through a science-first approach, combines standard clinical variables with quantitative, human-interpretable morphological features extracted from a single routine hematoxylin and eosin (H&E) slide. It was validated in two prospective, blinded cohorts from the CANTO and UNIRAD trials, involving a total of 633 patients. The model integrates four clinicopathologic factors and ten digital pathology descriptors, offering a transparent, reproducible method for risk stratification. Current clinical guidelines recommend adjuvant therapy escalation with CDK4/6 inhibitors for all patients with clinically high-risk ER+/HER2− early breast cancer. However, no widely available tool currently distinguishes those who truly benefit from intensified treatment from those who may do just as well with standard chemotherapy and endocrine therapy alone. This gap leaves many patients exposed to avoidable toxicity without clinical advantage. The study’s key results show that approximately one in five patients classified as high-risk by conventional criteria were reclassified as low-risk by the assay. These patients demonstrated an impressive 95.4% freedom from distant recurrence at nine years—comparable to outcomes seen in the TAILORx trial for node-negative, intermediate-risk patients treated with endocrine therapy alone (approximately 94.5%). The low-risk group experienced a 79% relative reduction in metastatic events compared to the remaining high-risk patients (sHR 0.21; p < 0.001), confirming the assay’s strong prognostic value. The model’s robustness was demonstrated through analytical validation, showing 96–100% reproducibility across different tumor heterogeneity patterns, digital scanners, and laboratory protocols—critical for reliable deployment in diverse clinical settings. “Escalating therapy for every clinically high-risk case exposes many women to significant toxicity without benefit. This assay provides actionable, evidence-based insight that allows us to target treatment where it truly matters,” said Prof. Fabrice André, MD, PhD, Chief Scientific Officer at Gustave Roussy. “It could spare 30,000 women each year from unnecessary treatment.” Marvin Lerousseau, PhD, Chief Scientific Officer at Spotlight Medical, emphasized the study’s methodological rigor. “Our work shows that routine tumor slides contain rich, clinically meaningful prognostic signals that can be extracted using transparent, quantitative AI methods. The major strength lies in the fully locked model being validated under blinded conditions in two independent, prospective trials, with consistent results across distinct patient populations.” The study, titled “Identifying patients with low relapse rate despite high-risk ER+/HER2− early breast cancer: development and validation of a clinicopathological assay,” was published online in the Journal of Clinical Oncology on August 25, 2025. Spotlight Medical is a French oncology diagnostics company focused on developing clinical-grade AI assays that enhance precision in cancer treatment selection. The company prioritizes rigorous clinical validation and algorithm transparency to extend the capabilities of pathology in real-world practice. For more information, visit spotlightmedical.com and follow Spotlight Medical on LinkedIn.