The assay identifies a biologically low-risk subgroup within clinically high-risk patients, with outcomes similar to stage I disease, potentially sparing 30,000 women each year from unnecessary treatment intensification.
Spotlight Medical today announced that the Journal of Clinical Oncology has published a peer-reviewed study describing a clinicopathologic assay that identifies a sizeable subgroup of patients labelled clinical high risk (ER-positive, HER2-negative early breast cancer) who have a favourable long term prognosis after standard chemo-endocrine therapy alone. The study reports blinded validation on two prospective cohorts from the CANTO and UNIRAD trials.
Unmet need. Current guidelines recommend adjuvant escalation with CDK4/6 inhibitors for clinically high-risk ER+/HER2− disease, yet no routinely available tool reliably distinguishes patients who may do well with endocrine therapy plus chemotherapy alone. The newly published work addresses this clinical gap by combining routine clinical variables with human-interpretable morphology descriptors derived from a single H&E slide. The model integrates 4 clinicopathologic variables and 10 quantitative digital pathology descriptors.
“Escalating therapy for every clinically defined high-risk case exposes many women to toxicity without benefit. This assay provides actionable insight that lets us target treatment where it truly helps, potentially sparing 30,000 women each year from unnecessary toxicity,” said Prof. Fabrice André, MD, PhD, Chief Scientific Officer of Gustave Roussy.
Key results (prespecified, blinded validation). On the combined CANTO+UNIRAD validation cohorts (n = 633), the assay classified about one in five patients as low-risk; 95.4% of these remained free of distant relapse at 9 years, a 79% relative reduction in metastatic events compared to the remaining patients (sHR 0.21; p < 0.001).
Context. The 9-year freedom from distant recurrence in this low-risk subgroup is comparable to outcomes reported in TAILORx for node-negative, intermediate-risk patients treated with endocrine therapy alone (≈94.5%), for whom escalation was not considered beneficial.
How it works. The fully locked model uses routinely collected clinicopathologic inputs and quantitative, human-interpretable morphology from a single H&E slide; multivariable analyses in the paper indicate the assay provides independent prognostic information beyond standard factors. Analytical validation showed 96–100% reproducibility across tumor heterogeneity, scanners, and lab protocols, enabling robust deployment in multicenter settings.
“Our study shows that routine tumor slides contain new, robust, and clinically meaningful prognostic signals that can be extracted with transparent quantitative methods,” said Marvin Lerousseau, PhD, Chief Scientific Officer at Spotlight Medical. “The major strength of this work lies in demonstrating a fully locked assay validated under blinded conditions in two prospective trials, with results that were consistent across distinct patient populations.”
Article details
Title: “Identifying patients with low relapse rate despite high-risk ER +/ HER2- early breast cancer: development and validation of a clinicopathological assay”
Journal: Journal of Clinical Oncology (online 25 August 2025).