Prognostic Value Of Adjuvant Chemotherapy In Early Triple Negative Breast Cancer:A Clinical Study And Meta Analysis

Obiective:(1)Adjuvant chemotherapy is an effective post-operative treatment for patients with triple negative breast cancer(TNBC).There is insufficient data in the elderly population to provide definitive chemotherapy recommendations.The aim of this study was to analyse the prognostic role of postoperative adjuvant chemotherapy(POCT)in elderly patients with stage I TNBC,to determine the relationship between POCT and survival and to provide a theoretical basis for clinical practice.(2)The efficacy of capecitabine in adjuvant chemotherapy for patients with TNBC is controversial.In this study,a randomised controlled trial(RCT)of the efficacy and safety of adding capecitabine to standard chemotherapy in patients with early-stage TNBC was conducted to assess whether adding capecitabine to TNBC improved clinical outcomes.Methods:(1)Based on the Surveillance,Epidemiology,and End Results(SEER)database,TNBC patients aged≥65 years from 2010 to 2016 were identified and divided into POCT group and non-POCT group.Propensity Score Matching(PSM)method was used to offset the differences in baseline characteristics between groups.Kaplan-Meier method was used to compare the overall survival(OS)and breast cancer-specific survival(BCSS)between the two groups.Cox proportional hazard model was constructed to evaluate the prognostic factors affecting OS and BCSS.(2)Search English online databases including Pub Med,EMBASE,and the Cochrane Library up to October 2022.All data in this study were extracted from RCT articles.Detailed survival data were extracted from the results of the article and summarized as HR and corresponding 95%CI to compare the survival rates between the capecitabine group and the control group.Q statistics and I~2test were used to evaluate the heterogeneity between studies.The HR and 95%CI of the relevant survival period were extracted and converted into log HR and SE for statistics and forest mapping.In addition,we used Egger’s test and funnel plot to evaluate publication bias.All statistical analyses were conducted using Stata 12.0 software.Results:(1)A total of 3307 female TNBC patients aged≥65 years were included.The results showed that younger age,higher histological grade,married,postoperative radiotherapy,mass resection,larger tumor and recent diagnostic year were associated with increased use of adjuvant chemotherapy(P<0.05).After PSM,POCT could significantly increase the 5-year OS of patients[HR=0.571,95%CI:0.432-0.753,P<0.001],but there was no significant difference in BCSS improvement[HR:0.793,95%CI(0.531-1.184),P=0.257].Exploratory subgroup analysis showed that POCT helped to improve OS in elderly patients with stage IA and IB(P<0.05),but could not improve BCSS in elderly patients with stage IA and IB(P>0.05).(2)A total of 8 RCTs involving 1633 patients were included.On this basis,adding capecitabine can improve the OS of TNBC patients[HR=0.71,95%CI(0.59,0.85),P<0.0001],DFS[HR=0.75,95%CI(0.64,0.89),P=0.001],RFS[HR=0.62,95%CI(0.47,0.81),P=0.001],DMFS[HR=0.61,95%CI(0.44,0.85),P=0.003]in TNBC patients.Subgroup analysis showed that the experimental group improved the OS of patients in Europe(P=0.002)and Asia(P=0.021),3-4 cycles of chemotherapy(P=0.001),postoperative chemotherapy(P=0.001),TNBC patients as subgroup(P<0.0001),and anthracycline and taxane as standard regimen(P=0.001).And it can improve the DFS of patients with 6-8 cycles of chemotherapy(P=0.047),TNBC patients as the whole cohort(P=0.002),anthracycline and taxane as the standard regimen(P=0.006),and lymph node negative(P=0.012).Safety analysis showed that there was no significant difference in the risk of grade 3 to4 adverse events in the capecitabine group[RR=1.74,95%CI(0.76,3.99),P=0.186].Subgroup analysis demonstrated a significantly increased risk of grade 3-4 hand-foot syndrome adverse events in the trial group compared to the control group(P<0.0001).Conclusion:(1)POCT can improve the OS of stage I TNBC patients over 65 years old,but further exploration is needed through larger prospective trials.(2)Adding capecitabine to standard chemotherapy is more effective for TNBC patients,but its safety is poor.In the future,more high-quality RCTs are needed to further explore the target patients for potential treatment,as well as the optimal dose and course range of capecitabine.