Boehm Kevin M, El Nahhas Omar S M, Marra Antonio, Waters Michele, Jee Justin, Braunstein Lior, Schultz Nikolaus, Selenica Pier, Wen Hannah Y, Weigelt Britta, Paul Evan D, Cekan Pavol, Erber Ramona, Loeffler Chiara M L, Guerini-Rocco Elena, Fusco Nicola, Frascarelli Chiara, Mane Eltjona, Munzone Elisabetta, Dellapasqua Silvia, Zagami Paola, Curigliano Giuseppe, Razavi Pedram, Reis-Filho Jorge S, Pareja Fresia, Chandarlapaty Sarat, Shah Sohrab P, Kather Jakob Nikolas
Computational Oncology Service, Memorial Sloan Kettering Cancer Center, 323 E 61 St, New York, NY, USA.
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA.
Nat Commun. 2025 Mar 2;16(1):2106. doi: 10.1038/s41467-025-57283-x.
The Oncotype DX® Recurrence Score (RS) is an assay for hormone receptor-positive early breast cancer with extensively validated predictive and prognostic value. However, its cost and lag time have limited global adoption, and previous attempts to estimate it using clinicopathologic variables have had limited success. To address this, we assembled 6172 cases across three institutions and developed Orpheus, a multimodal deep learning tool to infer the RS from H&E whole-slide images. Our model identifies TAILORx high-risk cases (RS > 25) with an area under the curve (AUC) of 0.89, compared to a leading clinicopathologic nomogram with 0.73. Furthermore, in patients with RS ≤ 25, Orpheus ascertains risk of metastatic recurrence more accurately than the RS itself (0.75 vs 0.49 mean time-dependent AUC). These findings have the potential to guide adjuvant therapy for high-risk cases and tailor surveillance for patients at elevated metastatic recurrence risk.
Oncotype DX®复发评分（RS）是一种针对激素受体阳性早期乳腺癌的检测方法，具有广泛验证的预测和预后价值。然而，其成本和滞后时间限制了全球范围内的采用，并且以往使用临床病理变量来估计它的尝试取得的成功有限。为了解决这一问题，我们收集了三个机构的6172例病例，并开发了Orpheus，这是一种多模态深度学习工具，用于从苏木精和伊红（H&E）全切片图像推断RS。我们的模型识别出TAILORx高危病例（RS>25）的曲线下面积（AUC）为0.89，而领先的临床病理列线图的AUC为0.73。此外，在RS≤25的患者中，Orpheus比RS本身更准确地确定转移复发风险（平均时间依赖性AUC为0.75对0.49）。这些发现有可能指导高危病例的辅助治疗，并为转移复发风险升高的患者定制监测方案。
