Evaluation And Clinical Significance Of Circulating Tumor Cells In Neoadjuvant Therapy Of Breast Cancer

Objective:In this study,subtraction enrichment and immunostaining fluorescence in situ hybridization（SE-i FISH）were used to detect the count of circulating tumor cell（CTC）in peripheral blood of female patients with invasive breast cancer who received neoadjuvant therapy（NAT）.By analyzing the changes of CTC before and after NAT and the relationship between the changes of CTC before and after NAT and the efficacy of NAT,to explore the evaluation and clinical significance of CTC in the efficacy of breast cancer NAT.Methods:According to the inclusion and exclusion criteria,82 female patients with invasive breast cancer who received NAT from December2019 to August 2021 in the Department of Breast Surgery of the Affiliated Hospital of Jining Medical University were studied.The response evaluation criteria in solid tumor were used to evaluate the efficacy after the second and fourth cycles of NAT.All patients with CR,PR and SD completed 6 cycles of treatment,such as changing treatment regimens or surgical treatment for patients with SD.Venous blood 6mL was collected from 82 patients before and after NAT,and the peripheral blood CTC count was detected by SE-i FISH technique.Pathological evaluation（Miller-Payne grading system）was used to evaluate the efficacy of NAT.Statistical analysis was used to analyze the relationship between the detection of CTC before NAT and the clinicopathological factors of patients,the changes of CTC before and after NAT,and the relationship between the changes of CTC before and after NAT and the efficacy of NAT.The consistency between CTC detection and pathological evaluation was evaluated.Results:In 82 patients with invasive breast cancer,the detection rate of CTC in peripheral blood before NAT was 68.3%（56/82）,which was related to TNM stage（P=0.018）and HER-2 expression status（P=0.040）.The detection rate of CTC in peripheral blood was higher in patients with late TNM stage and HER-2 positive.The detection of CTC in peripheral blood was not related to the patient’s age,BMI,menopausal status,tumor size,ER,PR,Ki67 expression and molecular typing（P>0.050）.The positive rate of CTC after NAT（39.0%）was significantly lower than that before NAT（68.3%）（P<0.001）.The CTC count after NAT was significantly lower than that before NAT（Z=-3.865,P<0.001）.The efficacy of NAT was evaluated by pathological evaluation（Miller-Payne grading system）.There were significant differences in the effective rate of CTC among the four groups of patients with positive-positive,positive-negative,negative-positive and negative-negative results before and after NAT（χ~2=14.181,P=0.002）.In the positive-positive group,the effective rate of CTC count before and after NAT in the reduced group（100%）was significantly higher than that in the non-reduced group（33.3%）（P<0.001）.The decrease of CTC count after NAT was positively correlated with MP grade（r=0.517,P<0.001）.Among the 82 patients,the overall effective rate of NAT was 69.5%（57/82）,of which the p CR rate was 25.6%（21/82）.The consistency between CTC detection and pathological evaluation was moderate（Kappa=0.415,P<0.001）.The sensitivity,specificity and accuracy of the CTC test for NAT efficacy were 64.9%（37/57）,84.0%（21/25）and 70.7%（58/82）respectively.The cases of negative CTC before and after NAT were excluded,and the consistency between CTC detection and pathological evaluation was significant（Kappa=0.681,P<0.001）.The sensitivity,specificity and accuracy of CTC test for NAT efficacy were 86.0%（37/43）,77.8%（14/18）and 83.6（51/61）respectively.Conclusion:1.SE-i FISH technique can effectively detect CTC in peripheral blood of patients with invasive breast cancer with high sensitivity.2.The detection of CTC is related to TNM stage and HER-2expression status.The CTC detection rate was higher in patients with invasive breast cancer with late staging and HER-2 positive.3.NAT can clear CTC in peripheral blood of patients with invasive breast cancer,the better the efficacy of NAT,the easier it is to clear CTC.The changes of CTC before and after NAT can effectively reflect the curative effect of NAT.4.CTC detection is a potential new method to evaluate the efficacy of NAT.It is suggested that dynamic monitoring of CTC should be used as an index to evaluate the efficacy of NAT to guide individual treatment.