Exploring The Possibility Of TNM Staging Update For Synchronous Solitary Distant Lymph Node Metastasis Breast Cancer

Objective: Currently,the AJCC 8th edition of TNM staging considers breast cancer with synchronous solitary distant lymph node metastasis(SDLNM)as advanced breast cancer.However,several studies suggest that it is more likely to be a locally advanced disease in terms of the prognosis and treatment.In order to resolve this controversy,we tried to investigate the prognosis of breast cancer patient with synchronous SDLNM and explore the optimal treatment.Methods: Breast cancer patients with TnN3cM0 stage or oligometastasis diagnosed between 2010 and 2016 were extracted by using the Surveillance,Epidemiology,and End Results(SEER)program.Kaplan-Meier(KM)method was used to compare the overall survival(OS)prognosis of patients in different TNM stages,and Cox forward regression was used to further evaluate the hazard ratio(HR).Fine-Gray test was used to compare breast cancer specific survival(BCSS)outcomes.We also used propensity score matching(PSM)to balance other confounders.Synchronous SDLNM patients were then randomly assigned into the training and test groups in a ratio of 6:4.In the training group,independent prognostic factors were screened by univariate and multivariate Cox analysis,and they were used to establish a nomogram to predict OS prognosis,while the test group was used for validation.C-index,calibration curve,and ROC curve were used to evaluate the model predicted performance.For patients undergoing mastectomy,Cox risk regression analysis was used to evaluate the effects of post-operative radiotherapy and chemotherapy after adjusting for other factors.Results: 1.9539 breast cancer patients were enrolled in this study,including 497 cases of TnN3cM0,692 cases of synchronous SDLNM,and 8350 cases of other oligometastasis.The median age of all patients was 58(IQR 49-66)years,and the median follow-up was 23(IQR 11-41)months.2.KM curves and log-rank test showed that the prognosis of synchronous SDLNM patients was similar to that of TnN3cM0 patients,which was better than that of patients with other oligometastasis.Cox stepwise regression analysis adjusted other variables and showed us that the prognosis of synchronous SDLNM patients was similar to that of patients in stage TnN3cM0: SDLNM vs.TnN3cM0:p=0.778;SDLNM vs.other oligometastasis: HR 0.767,95%CI,0.672-0.875,p<0.001.Moreover,the result of the Fine-Gray test for BCSS was similar.After adjusting for confounders via using PSM,the results remained consistent(SDLNM vs.TnN3cM0,OS:P=0.916;BCSS:p= 0.440).3.692 synchronous SDLNM patients were randomly assigned,including 416 in training group and 276 in test group.In the training group,univariate and multivariate Cox survival analyses demonstrated that marriage,race,SBR grade,T stage,molecular subtype,surgery and radiotherapy were independent prognostic factors for OS,among which molecular subtype could bring the greatest impact.Above characteristics were utilized to construct a nomogram to predict patients’ 1-year,3-year,and 5-year OS probabilities.The C-index of the model was 0.731(95%CI0.692-0.770)in the training group and 0.722(95%CI 0.671-0.773)in the test group.The areas under the ROC curves(AUC)were all greater than 0.7,indicating that the model had a superior predictive discrimination.Calibration curves indicated the well predictive accuracy.4.For patients who underwent mastectomy,KM method and Cox multivariate survival analysis signified a significantly increased risk of death among those who did not receive chemotherapy or post-operative radiotherapy(without chemotherapy: HR,1.973;95% CI,1.033 to 3.769;P=0.040;without post-operative radiotherapy: HR,1.669;95%CI,1.102～2.529;P= 0.016).Conclusions: 1.The prognosis of synchronous SDLNM breast cancer was similar with that of breast cancer in stage TnN3cM0.It should be classified as a locally advanced disease.Different molecular subtypes may have different outcomes in this patient population.2.Mastectomy brought significant survival advantage for synchronous SDLNM breast cancer patients compared with lumpectomy.Chemotherapy and post-radiotherapy may prolong OS prognosis.3.The established nomogram has well distinguishing ability and accuracy,which can provide help for clinical decision making.