Study On The Relationship Between Lymphocyte And Monocyte In Peripheral Blood And Tissue And Prognosis In Patients With Early-stage Triple-negative Breast Cancer

Breast cancer is one of the most common malignant tumor in women.It harm seriously the physical and mental health of women.In the United States and Europe,breast cancer has a high incidence and account for 25%-30%of malignancy.China is not a country with high incidence of breast cancer,but the incidence increases significantly in recent years,and the age of the disease is becoming younger.Therefore,doctors focus on the diagnosis and prognosis of breast cancer.Triple-negative breast cancer(TNBC)is the breast cancer lack of estrogen receptor(ER),progesterone receptor(PR)and human epidermal growth factor receptor(HER2)expression,accounting for about 10-20%of all breast cancer.Compared with other pathological types of breast cancer,patients with TNBC are younger,tumor diameter greater,poor differentiation,higher nuclear fission count,and TP53 mutations are more common.Overall survival(OS)and disease-free survival(DFS)are worse.In view of the biological progression of TNBC and the poor efficacy of current targeted therapy,chemotherapy is still the main method for the treatment of TNBC.Recently,a large number of studies on gene expression profiles have divided TNBC into different prognostic subgroups.However,in clinical practice,gene expression profiling is not able to further determine the TNBC cancer biology and poor prognosis.Studies suggest that chronic systemic inflammation is associated with cancer,and a poor prognosis.including TNBC.Lymphocytes and macrophages are the key immune cells in the inflammatory response.The former plays an important role in inhibiting tumor cell proliferation,migration and inducing cytotoxicity.The infiltration of lymphocytes in tumor tissue is related to the better prognosis of all kinds of malignant tumors.In contrast,tumor associated macrophages(TAMs),derived from circulating monocytes,have been reported to have a low survival rate associated with many types of cancer.It has been shown that Lymphocyte to mononuclear ratio(LMR)is a independent prognostic factor in many types of cancer,including hematological malignancies,gastrointestinal malignant tumors,nasopharyngeal carcinoma,and non small cell lung cancer.Recently,a retrospective study has indicated that elevated LMR is associated with better survival in patients with locally advanced breast cancer after neoadjuvant chemotherapy.Recent studies have shown that the lymphocyte to monocyte ratio(LMR)is a useful prognostic factor in various cancers.Because there is no clinical prognostic predictor in patients with TNBC,The purpose of the current study was to investigate the association between lymphocyte and monocyte in peripheral blood and tissue,disease-free survival(DFS),and overall survival(OS)in patients with early-stage(I to III)triple-negative breast cancer(TNBC).Cancer tissues and pretreatment LMR with corresponding clinical features from230 TNBC patients were noted.A receiver operating characteristic(ROC)curve for survival prediction was plotted to verify the optimal cutoff values for LMR,lymphocyte,and monocyte counts.The difference between variables was calculated using chi-square tests.The Kaplan–Meier method and univariate and multivariate Cox regression models were applied to assess OS and DFS.Based on the ROC analysis,the optimal cutoff point for LMR was 4.7.Associations between high LMR(≥4.7)and significantly small tumor size(P=0.005)and TNM stage(P=0.013)were found,although there was no significant association for other clinical pathological factors.In the multivariate analysis,LMR was a significant predictive factor for both OS(hazard ratio[HR]=0.42;95%confidence interval[CI],0.19–0.95;P<0.001)and DFS(HR=0.40;95%CI,0.20–0.79;P<0.001).Immunohistochemical show the relationship between the expression of CD8 and CD20 labeled tumor associated lymphocytes in breast cancer tissues and pathological characteristics,and the expression of CD68 labeled tumor associated lymphocytes in breast cancer tissues and pathological characteristics.The results showed CD8 and CD20 were positively expressed in T lymphocytes and B lymphocytes in breast cancer tissues,respectively.The high expression of CD8 is negatively related to some clinicopathological features of breast cancer,and CD20 is independent of the clinicopathological features of breast cancer.CD68 was positively expressed in macrophages of breast cancer tissues.The high expression of CD68 is positively related to some clinicopathological features of breast cancer.In addition,the predictive values of the OS and DFS were also observed for absolute counts of lymphocytes(P<0.001)and monocytes(P<0.001).Our study suggests that pretreatment LMR may be a predictive factor for long-term survival in patients with early-stage TNBC.Part 1 Study on the relationship between lymphocyte in peripheral blood and tissue and prognosis in patients with early-stage triple-negative breast cancerObjective:To study the relationship between lymphocyte in peripheral blood and tissue and prognosis in patients with early-stage triple-negative breast cancerMethods:230 patients were followed up.The median follow-up duration was 4.3years.Record the date of ALC for each patients.Immunohistochemical show the relationship between the expression of CD8 and CD20 labeled tumor associated lymphocytes in breast cancer tissues and pathological characteristics.Two-sided P values<0.05 were defined as statistically significant.The Kaplan-Meier method was used to estimate the DFS and OS curves,and the log-rank test was used to compare associations between groups.The chi-square test was used to compare qualitative variables.Results:The optimal cutoff point of ALC is 1.6×10~9/L.The OS and DFS of high ALC groups were 8.8,7.1 years,respectively.The OS and DFS of low ALC groups were5.5,4.4 years,respectively.CD8 and CD20 were positively expressed in T lymphocytes and B lymphocytes in breast cancer tissues,respectively.The high expression of CD8 is negatively related to some clinicopathological features of breast cancer,and CD20 is independent of the clinicopathological features of breast cancer.Conclusion:The OS and DFS of high ALC groups were longer than low ALC groups.CD8and CD20 were positively expressed in T lymphocytes and B lymphocytes in breast cancer tissues,respectively.The high expression of CD8 is negatively related to some clinicopathological features of breast cancer,and CD20 is independent of the clinicopathological features of breast cancer.It showed a good prognosis when the number of lymphocyte increased.Part 2 Study on the relationship between monocyte in peripheral blood and tissue and prognosis in patients with early-stage triple-negative breast cancerObjective:To study the relationship between monocyte in peripheral blood and tissue and prognosis in patients with early-stage triple-negative breast cancerMethods:230 patients were followed up.The median follow-up duration was 4.3 years.Record the date of AMC for each patients.Immunohistochemical show the relationship between the expression of CD68 labeled tumor associated lymphocytes in breast cancer tissues and pathological characteristics.Two-sided P values<0.05 were defined as statistically significant.The Kaplan-Meier method was used to estimate the DFS and OS curves,and the log-rank test was used to compare associations between groups.The chi-square test was used to compare qualitative variables.Results:The optimal cutoff point of AMC is 0.5×10~9/L.The OS and DFS of low AMC groups were 8.3,6.5 years,respectively.The OS and DFS of high AMC groups were7.0,4.8 years,respectively.CD68 was positively expressed in macrophages of breast cancer tissues.The high expression of CD68 is positively related to some clinicopathological features of breast cancer.Conclusion:The OS and DFS of low AMC groups were longer than high AMC groups.CD68 is positively expressed in macrophages of breast cancer tissues.The high expression of CD68 is positively related to some clinicopathological features of breast cancer.It showed a bad prognosis when the number of monocyte increased.Part 3 Study on the relationship between lymphocyte to monocyte ratio in peripheral blood and prognosis in patients with early-stage triple-negative breast cancerObjective:To study the relationship between pretreatment peripheral lymphocyte to monocyte ratio and prognosis in patients with early-stage triple-negative breast cancerMethods:230 patients were followed up.The median follow-up duration was 4.3 years.Record the date of LMR for each patients.Two-sided P values<0.05 were defined as statistically significant.The univariate and multivariate Cox proportional hazard regression model were used to test associations between LMR and other potential prognostic factors with the DFS and OS in patients.The Kaplan-Meier method was used to estimate the DFS and OS curves,and the log-rank test was used to compare associations between groups.The chi-square test was used to compare qualitative variables.Results:The optimal cutoff point of LMR is 4.7.In high LMR groups,the tumor volume is smaller and the clinical stage is earlier.The OS and DFS of high LMR groups were9.0,7.2 years,respectively.The OS and DFS of low LMR groups were 6.9,5.1 years,respectively.Conclusion:The OS and DFS of high LMR groups were longer than low LMR groups.The pretreatment peripheral LMR could function as an independent prognostic factor for the OS and DFS.