Development and validation of an integrated model combining deep learning, radiomics, and clinical and breast ultrasound features for Breast Imaging Reporting and Data System 4A lesion malignancy classification.

Background: The subjective assessment of Breast Imaging Reporting and Data System (BI-RADS) 4A lesions leads to a high number of unnecessary biopsies, highlighting the need for more objective and accurate diagnostic tools. This study aimed to construct and validate a novel multimodal framework that integrates deep learning (DL), radiomics, and clinical and breast ultrasound (US) features to distinguish between benign and malignant breast lesions classified as BI-RADS 4A. Methods: A total of 935 patients with pathologically confirmed BI-RADS 4A lesions were retrospectively enrolled and randomly divided into a training cohort (n=654) and an internal validation cohort (n=281). An additional 488 patients were enrolled as the external validation cohort. DL and radiomics models were developed with the light gradient boosting machine (LightGBM) algorithm, a machine learning technique known for its efficiency in handling high-dimensional data. Univariate and multivariate logistic regression (LR) analyses identified significant clinical and US features. After handcrafted radiomics features, DL features, and clinical/breast US features were combined, dimensionality reduction and feature selection were performed. The integrated model was developed via LightGBM, and the SHapley Additive Explanations (SHAP) approach was applied to rank feature contributions. Results: The integrated model achieved robust discrimination between benign and malignant BI-RADS 4A lesions, with an area under the curve (AUC) of 0.938, 0.870, and 0.861 for the training cohort, internal validation cohort, and external validation cohort, respectively. Furthermore, in the external validation cohort, the integrated model significantly outperformed the handcrafted radiomics model (AUC =0.719; P<0.001) and the DL model (AUC =0.763; P=0.011). Decision curve analysis confirmed that the integrated model was the most clinically useful across the three cohorts. Conclusions: The integrated model demonstrated high accuracy in differentiating between benign and malignant BI-RADS 4A lesions, exhibiting the ability to significantly reduce unnecessary biopsies while maintaining diagnostic accuracy.