Attention-based multimodal fusion transformer for predicting the efficacy of neoadjuvant therapy in breast cancer: a cross-institutional retrospective study.

backgroundNeoadjuvant therapy (NAC) is a standard treatment for breast cancer, yet only some patients gain significant benefit. Identifying those most likely to benefit from NAC is crucial. Single-modality data often overlook patient heterogeneity, so we developed an interpretable, attention-based multimodal full information feature fusion transformer, MuFi, to predict NAC responses by integrating whole slide images (WSI) and magnetic resonance imaging (MRI).

methodsData from 567 biopsy-confirmed breast cancer patients from two institutions were retrospectively analyzed, with a training cohort (n = 290), validation cohort (n = 73), and external test cohort (n = 204). Multimodal data included pre-treatment pathology slides, MRI scans, and clinical information. A memory-efficient multimodal model was used to fuse WSIs and MRI, with a transformer capturing interactions between histological patches and MRI features.

resultsMuFi achieved AUCs of 81.9% and 78.5% in discovery and validation cohorts and 79.3% in external testing, outperforming clinical, single-modality and late-fusion-based models. Integrating clinical data (cT and molecular subtype) with MuFi and Feature Re-calibration based Multiple Instance Learning (FRMIL) models further increased AUCs to 90.2%, 81.8%, and 81.6% across the cohorts, indicating enhanced predictive accuracy and generalizability, especially in external testing.

conclusionBy fusing pathology and radiology features, MuFi improves decision reliability and identifies critical multimodal predictors. This integration framework better captures patient heterogeneity, supporting personalized NAC decision-making through improved accuracy and generalizability.