PURPOSE:We aimed at assessing the predictive ability of ultrasound-based radiomics combined with clinical characteristics for axillary lymph node (ALN) status in early-stage breast cancer patients and to compare performance in different peritumoral regions. MATERIALS AND METHODS:A total of 755 patients (527 in the primary cohort and 228 in the external validation cohort) were enrolled in this study. Ultrasound images for all patients were acquired and radiomics analysis performed for intratumoral and different peritumoral regions. The MRMR and LASSO regression analyses were performed on extracted features from the primary cohort to construct a radiomics signature formula combined with clinical characteristics. Pearson's coefficient and the variance inflation factor (VIF) were performed to check the correlation and the multicollinearity among the final predictors. The best performing model was selected to develop a nomogram, which was established by performing binary logistic regression and acquiring cut-off values based on the corresponding nomogram scores of the masses. RESULTS:Among all the radiomics models, the "Mass + Margin3mm" model exhibited the best performance. The areas under the curves (AUC) of the nomogram in the primary and external validation cohorts were 0.906 (95% confidence intervals [CI] 0.882-0.930) and 0.922 (95% CI 0.894-0.960), respectively. They both showed good calibrations. The nomogram exhibited a good ability to discriminate between positive and negative lymph nodes (AUC: 0.853 (95% CI 0.816-0.889) in primary cohort, 0.870 (95% CI 0.818-0.922) in validation cohort), and between low-volume and high-volume lymph nodes (AUC: 0.832 (95% CI 0.781-0.884) in primary cohort, 0.911 (95% CI 0.858-0.964) in validation cohort). CONCLUSIONS:The established nomogram is a prospective clinical prediction tool for non-invasive assessment of ALN status. It has the ability to enhance the accuracy of early-stage breast cancer treatment.