Development of a Nomogram to Predict N2 or N3 Stage in T1-2 Invasive Breast Cancer Patients with No Palpable Lymphadenopathy

Purpose: Subsequent to the American College of Surgeons Oncology Group (ACOSOG) Z0011 and After Mapping of the Axilla: Radiotherapy or Surgery (AMAROS) trials, complete axillary lymph node dissection is not routinely performed, even in cases where metastatic sentinel lymph nodes are detected. We investigated the percentage of N2 or N3 stages in T1-2 invasive breast cancer patients with no lymphadenopathy and developed a nomogram to predict the possibility of N2 or N3 stages in these patients. Methods: We retrospectively reviewed the charts of invasive breast cancer patients who were clinically NO stage, but had a positive sentinel or non-sentinel lymph node detected on sentinel lymph node biopsy. The association of potential risk factors with known outcomes (N2 or N3 stages) was tested using logistic regression analysis. Variables with p <0.05 in the multivariate analysis were included in the nomogram. Internal performance validation was carried out using a 5-fold cross validation method. Results: Among a total of 1,437 patients, 1,355 patients had stage N1 disease (94.3%), while 82 had stage N2 or N3 disease (5.7%). Multivariate stepwise logistic regression analysis revealed lymphovascular invasion (p=0.008), T2 stage (p=0.026), metastatic lymph node ratio (p<0.001), and perinodal extension (p<0.001) as independent predictors of N2 or N3 stages. A nomogram was developed based on these factors. The area under the curve estimated from the receiver operating characteristic graph was 0.8050 in the model set and 0.8246 in the test set. Conclusion: Our nomogram can be employed for the prediction of N2 or N3 stage among cases fulfilling the ACOSOG Z0011 or AMAROS criteria.