Prediction of OncotypeDX recurrence score using H&E stained WSI images

The OncotypeDX 21-gene assay is a widely adopted tool for estimating recurrence risk and informing chemotherapy decisions in early-stage, hormone receptor-positive, HER2-negative breast cancer. Although informative, its high cost and long turnaround time limit accessibility and delay treatment in low- and middle-income countries, creating a need for alternative solutions. This study presents a deep learning-based approach for predicting OncotypeDX recurrence scores directly from hematoxylin and eosin-stained whole slide images. Our approach leverages a deep learning foundation model pre-trained on 171,189 slides via self-supervised learning, which is fine-tuned for our task. The model was developed and validated using five independent cohorts, out of which three are external. On the two external cohorts that include OncotypeDX scores, the model achieved an AUC of 0.825 and 0.817, and identified 21.9% and 25.1% of the patients as low-risk with sensitivity of 0.97 and 0.95 and negative predictive value of 0.97 and 0.96, showing strong generalizability despite variations in staining protocols and imaging devices. Kaplan-Meier analysis demonstrated that patients classified as low-risk by the model had a significantly better prognosis than those classified as high-risk, with a hazard ratio of 4.1 (P<0.001) and 2.0 (P<0.01) on the two external cohorts that include patient outcomes. This artificial intelligence-driven solution offers a rapid, cost-effective, and scalable alternative to genomic testing, with the potential to enhance personalized treatment planning, especially in resource-constrained settings.