| Background:Studies have shown that surgery for primary tumors can benefit the overall survival(OS)of de novo stage Ⅳ breast cancer patients.However,the sequencing of surgery and systemic therapy in the first course of treatment for de novo stage Ⅳ breast cancer patients are currently inconclusive.This article mainly studies the effects of preoperative systemic therapy and postoperative systemic therapy on the OS of de novo stage Ⅳ breast cancer patients.In addition,we proposed a broadly applicable clinical prognostic model for these patients to accurately predict their overall survival(OS).Methods:The 3278 de novo stage Ⅳ breast cancer patients who underwent surgery and systemic therapy between 2010 and 2015 were all from the Surveillance,Epidemiology,and End Results(SEER)cancer registry.Propensity score matching(PSM)is used to balance the baseline characteristics of patients in pre-ST group and post-ST group.Univariate and multivariate Cox regression analyses are used to determine survival-related factors.The OS of pre-ST group and post-ST group was evaluated by Kaplan-Meier chart and Cox proportional hazard regression model.Forest plots showed the results of the hierarchical analysis.In addition,a nomogram was proposed by the least absolute shrinkage and selection operator(LASSO)multiple Cox regression analysis,and C-index,the ROC curve,calibration curve and survival curve were used to verify the discrimination and calibration of the nomogram.Results:(1)Compared with post-ST,pre-ST had a lower risk of death,with median survival of 49 months and 56 months,respectively(HR 0.83;95%CI 0.74-0.93;P=0.0018).Subgroup analysis showed that in patients over 60 years of age(HR 0.73;95%CI 0.61-0.88;P=0.001),tumor size(≤5cm)(HR 0.79;95%CI 0.66-0.94;P=0.009),fewer positive regional nodes number(≤3)(HR 0.76;95%CI 0.65-0.90;P=0.001),HR+/HER2’(HR 0.85;95%CI 0.730.99;P=0.038),bone-only metastases(HR 0.81;95%CI 0.68-0.97;P=0.019)and liver-only metastases(HR 0.65;95%CI 0.43-0.97;P=0.033),the overall risk of death was reduced in pre-ST versus post-ST in the population.However,in aged ≤60 years,positive regional nodes number(>4),TNBC,HR+/HER2+,HR-/HER2+,brain-only metastases,lung-only metastases,other sites,and any site,there was no significant difference in OS between pre-ST and post-ST(P>0.05).(2)This study was finally enrolled 2916 de novo stage Ⅳ breast patients,who were randomly divided into a training set(n=2044)and a validation set(n=872)according to the ratio of 7:3.After the initial 10 clinical variables were regressed by LASSO-Cox regression,8 clinical factors were screened out.These variables were age,race,married,subtype,grade,T stage,the first course of treatment,and de novo metastatic site.After multivariate Cox regression analysis,race was excluded.Seven variables were finally identified as independent OS-related factors in de novo stage Ⅳ breast cancer patients.1-year,3-year,and 5-year nomograms of de novo stage Ⅳ breast cancer patients were proposed based on those independent prognostic variables.The C-index of the nomogram is 0.70.The 1-year,3-year and 5-year area under curve(AUC)of training set were 0.775,0.760 and 0.743,respectively.The 1-year,3-year,and 5-year AUCs of the validation set were 0.747,0.727,and 0.712,respectively.The calibration curve verified the good consistency of the nomogram.According to nomogram risk stratification,the prognosis of patients in high,medium and low risk groups was significantly different(P<0.01).Conclusion:(1)In conclusion,we found that the sequencing of surgery and systemic therapy in the first course of treatment affects prognosis of de novo stage Ⅳ breast cancer patients.Compared with post-ST,pre-ST can prolong OS of de novo stage Ⅳ breast cancer patients.(2)The nomogram in this study can predict the risk of 1-year,3-year and 5-year OS with good accuracy in de novo stage Ⅳ breast cancer patients undergoing surgery and systemic therapy in the first treatment,which can help clinicians to formulate more precise and individualized treatment strategies. |
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