Lumi-Guide: An Artificial-Intelligence-Driven Multimodal Framework for Optimizing Personalized Neoadjuvant Therapy Decision-Making in Luminal Breast Cancer.

Accurate prediction of pathological complete response (pCR) to neoadjuvant therapy in luminal breast cancer remains challenging, hindering precise treatment decisions. Here, we present the Lumi-Guide system, a novel multimodal framework that integrates deep-learning-based MRI analysis with clinical and genomic data to enable personalized treatment selection. In this multicenter study, we analyzed 1,097 patients with luminal breast cancer from 6 international datasets. We developed a Swin Transformer-based Lumi-I model using 3-plane dynamic contrast-enhanced MRI data and integrated it with clinical factors to construct the Lumi-CI model, which demonstrated robust performance across the validation and 2 external test sets, with areas under the receiver operating characteristic curves of 0.810, 0.819, and 0.864, respectively. Radiogenomic analysis revealed distinct biological characteristics: The Lumi-I high-score group exhibited immunologically active and proliferative microenvironments, while the low-score group showed estrogen-response-driven signaling. To further enhance predictive accuracy, a genomic model (Lumi-G) based on 22 established RNA biomarkers was further developed and integrated with the Lumi-CI model to create a multimodal Lumi-CIG model. We subsequently designed a Lumi-Guide 2-step triage system that prioritizes clinical-imaging information (Lumi-CI) while selectively incorporating genomic data (Lumi-CIG) when beneficial, thus optimizing resource allocation. Critically, by integrating Lumi-Guide system prestratification with response-predictive-subtype-recommended therapies, patients predicted to achieve pCR demonstrated substantially higher actual pCR rates than controls across 3 treatment patterns: 77.8% vs. 61.5% (optimal treatment), 57.6% vs. 24.7% (non-optimal treatment), and 35.3% vs. 4.7% (double-negative response-predictive subtype). This clinically practical and biologically interpretable framework transforms personalized neoadjuvant therapy in luminal breast cancer into a scalable reality.