Predictions of Oncotype DX® High-Risk Classification Using Magnetic Resonance Imaging-Based Intratumoral Heterogeneity.

The Oncotype DX® 21-gene recurrence score (RS) guides adjuvant chemotherapy decisions in estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer, yet requires invasive tissue sampling and involves substantial costs. This study evaluated intratumoral tumor ecological diversity (iTED), a habitat imaging approach, as a non-invasive complement for predicting Oncotype DX® high-risk classification (RS > 25). This retrospective multi-center study included 312 patients with ER+/HER2- invasive breast cancer who underwent Oncotype DX® testing (development: n = 168; external validation: n = 144). The iTED framework employed superpixel-based habitat determination using Gaussian mixture models on pretreatment dynamic contrast-enhanced MRI. Four predictive models were compared: clinical, conventional whole-tumor radiomics (C-radiomics), iTED, and combined (Clinical + iTED). The iTED model achieved higher discriminative performance compared with C-radiomics in both development (area under the curve [AUC]: 0.868 ± 0.068 vs. 0.730 ± 0.112) and external validation (AUC: 0.811 vs. 0.587) sets. The combined model further improved performance (development AUC: 0.908 ± 0.043; external AUC: 0.889). Habitat imaging-based iTED features achieved numerically higher performance than conventional radiomics in predicting Oncotype DX® high-risk classification. These findings suggest the potential of iTED as a non-invasive imaging biomarker to support molecular testing in clinical decision-making.