BACKGROUND: To develop a predictive nomogram for breast cancer lympho-vascular invasion (LVI), based on digital breast tomography (DBT) data obtained from intra- and peri-tumoral regions. METHODS: One hundred ninety-two breast cancer patients were enrolled in this retrospective study from 2 institutions, in which Institution 1 served as the basis for training (n = 113) and testing (n = 49) sets, while Institution 2 served as the external validation set (n = 30). Tumor regions of interest (ROI) were manually-delineated on DBT images, in which peri-tumoral ROI was defined as 1 mm around intra-tumoral ROI. Radiomics features were extracted, and logistic regression was used to construct intra-, peri-, and intra- + peri-tumoral radiomics models. Patient clinical data was analyzed by both uni- and multi-variable logistic regression analyses to identify independent risk factors for the non-radiomics clinical imaging model, and the combination of both the most optimal radiomics and clinical imaging models comprised the comprehensive model. The best-performing model out of the 3 types (radiomics, clinical imaging, comprehensive) was identified using receiver operating characteristic (ROC) curve analysis, and used to construct the predictive nomogram. RESULTS: The most optimal radiomics model was the intra- + peri-tumoral model, and 3 independent risk factors for LVI, maximum tumor diameter (odds ratio [OR] = 1.486, 95% confidence interval [CI] = 1.082-2.041, P = 0.014), suspicious malignant calcification (OR = 2.898, 95% CI = 1.232 ~ 6.815, P = 0.015), and axillary lymph node (ALN) metastasis (OR = 3.615, 95% CI = 1.642-7.962, P <
0.001) were identified by the clinical imaging model. Furthermore, the comprehensive model was the most accurate in predicting LVI occurrence, with areas under the curve (AUCs) of 0.889, 0.916, and 0.862, for, respectively, the training, testing and external validation sets, compared to radiomics (0.858, 0.849, 0.844) and clinical imaging (0.743, 0.759, 0.732). The resulting nomogram, incorporating radiomics from the intra- + peri-tumoral model, as well as maximum tumor diameter, suspicious malignant calcification, and ALN metastasis, had great correspondence with actual LVI diagnoses under the calibration curve, and was of high clinical utility under decision curve analysis. CONCLUSIONS: The predictive nomogram, derived from both radiomics and clinical imaging features, was highly accurate in identifying future LVI occurrence in breast cancer, demonstrating its potential as an assistive tool for clinicians to devise individualized treatment regimes.