Analysis Of Risk Factors Of Non-sentinel Lymph Node Metastasis In Sentinel Lymph Node Positive Breast Cancer Patients:Development And Assessment Of A Predictive Nomogram

Objective: Analyze of risk factors of non-sentinel lymph node in breast cancer.We sought to establish a prediction model for risk of positive non-sentinel lymph nodes with sentinel lymph node metastasis and further validate the model in a separate validation cohort.The different models were validated in modeling cohort.Methods: We reviewed the clinicopathologic data of 495 breast cancer patients with sentinel lymph node metastasis who underwent axillary lymph node dissection at our hospital.Independent risks for non-sentinel lymph node metastasis were assessed in a training cohort by multivariate analysis and incorporated into a mathematical prediction model.The model was further validated in a separate validation cohort and a nomogram was developed and evaluated for diagnostic performance in predicting the risk of non-sentinel lymph node metastasis.Results: The AUC of MSKCC,Tenon,MDA,Ljubljana and Louisville models were 0.7613,0.7142,0.7076,0.7483 and 0.671,respectively.Tumor size,lymphovascular invasion,the size of SLN metastasis,number of positive SLNs,number of negative SLNs and the molecular subtype were correlated with NSLN metastasis.Multivariate regression analysis indicated that tumor size(OR=1.439;95%CI: 1.025-2.021;P= 0.036),sentinel lymph node macro-metastasis versus micro-metastasis(OR=5.063;95%CI: 1.111-23.074;P=0.036)and the number of positive SLNs(OR=2.583,95%CI: 1.714-3.892;P<0.001),the number of negative SLNs(OR=0.686,95%CI: 0.575-0.817;P<0.001)were independent statistically significant predictors of NSLN metastasis.Furthermore,luminal B was an independent and statistically significant predictor of non-sentinel lymph node metastasis versus luminal A(OR=3.311,95%CI: 1.593-6.884;P=0.001).HER2 overexpression was also an independent and statistically significant risk of non-sentinel lymph node metastasis(OR=4.308,95%CI: 1.097-16.912;P=0.036).A regression model based on the results of multivariate analysis was established to predict the risk of non-sentinel lymph node metastasis,which had an AUC of 0.8188..The area under the ROC curve in the validation population was 0.8075.Conclusion: The mathematical prediction model that incorporates five variables including breast cancer molecular subtype demonstrates excellent diagnostic performance in assessing the risk of non-sentinel lymph node metastasis in sentinel lymph node-positive patients.The prediction model could be of help surgeons in evaluating the risk of non-sentinel lymph node involvement for breast cancer patients;however,the model requires further validation in prospective studies.