Abstract Objective: The management of positive sentinel lymph node biopsies (SLNB) in patients with early-stage breast cancer remains a matter of controversy. Some studies have shown that not all breast cancer patients with positive sentinel lymph nodes (SLNs) benefit from further axillary lymph node dissection (ALND). Our study aims to analyse the risk factors and construct a new nomogram to predict non-sentinel lymph node (NSLN) metastasis in Chinese early-stage breast cancer patients with positive sentinel lymph nodes. Methods: The clinical data of 708 patients with early-stage breast cancer who attended The Fourth Hospital of Hebei Medical University for surgical treatment from January 2016 to December 2021 was retrospectively analyzed. All of them were female breast cancer patients with positive sentinel lymph nodes and underwent ALND. The patients were divided into modeling group and validation group according to the time of treatment. The patients in the modeling group were divided into a positive NSLN group and a negative NSLN group. The characteristics: age, maximum tumor diameter, the number of positive SLNs, proportion of positive SLNs, vessel carcinoma embolus, nerve invasion, status of ER, PR, HER-2 and Ki-67 were included in the analysis. And the independent risk factors of NSLN metastasis were screened by univariate (chi-square test) and multivariate (logistic regression) analysis. A nomogram model was established according to the screened independent risk factors, and the model was externally validated by the validation group. The ROC curve was plotted to calculate the area under the curve (AUC) and evaluate the predictive power of the nomogram model. A calibration curve and decision curve analysis (DCA) were used to evaluate the performance of the model. Results: Among the 708 patients, (modeling group n=410, validation group n=298), the average age, average number of positive SLNs, and NSLN positive rate were 50.9±11.1, 1.55±0.87 and 25.71%. The univariate analysis revealed statistically significant differences in the number of positive SLNs (P< 0.001), the proportion of positive SLNs (P < 0.001), vessel carcinoma embolus (P=0.001), nerve invasion (P=0.012), and ER status (P=0.029) in the NSLN-positive group compared with the negative group. The multifactorial logistic regression analysis revealed that the number of positive SLN (P=0.002; OR: 1.700; 95% CI: 1.219-2.370), the proportion of positive SLN (P=0.048; OR: 3.214; 95% CI: 1.001-10.490), vessel carcinoma embolus (P=0.010; OR: 2.076; 95% CI: 1.194-3.612), nerve invasion (P=0.024; OR: 2.119; 95% CI: 1.221-3.678), and ER status (P=0.045; OR: 2.978; 95% CI: 1.022-8.675) were independent risk factors for NSLN positivity. Furthermore, the nomogram was built using these 5 factors and validated on 298 patients in the validation group. The AUC was 0.728 (P< 0.001; 95%CI: 0.673-0.784) in the modeling group and 0.810 (P<0.001; 95%CI: 0.735-0.886) in the validation group. The calibration curves of the modeling and validation groups were close to the ideal curve, and DCA also showed that the model could be applied in clinical practice. Conclusion: For early-stage breast cancer with positive SLNs, these factors as the positive number of SLNs > 2, the ratio of positive SLNs > 50%, vessel carcinoma embolus, nerve invasion and ER-positive could predict NSLN metastasis well. The proposed nomogram appears to accurately estimate the likelihood of positive NSLNs and may greatly help the surgeon to decide intraoperatively whether to perform further ALND and avoid non-essential ALND as well as postoperative complications. Citation Format: Zhenchuan Song, Xueyi Zhao, Liu Yang. Risk factors and a new predictive nomogram for predicting the Non-sentinel Lymph Node Metastasis in 708 early-stage Breast Cancer Patients with Positive Sentinel Nodes in China [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-02-08.