Evaluation And Clinical Significance Of Circulating Tumor Cells And Circulating Tumor Cell HER-2 Detection In Breast Cancer Neoadjuvant Chemotherapy

Objective(s): Detect circulating tumor cells(CTCs)and circulating tumor cell HER-2(CTCs-HER2)in peripheral blood of breast cancer patients before and after neoadjuvant therapy(NAT),and analyze the relationship between CTCs before NAT and clinicopathological indicators of breast cancer patients.To analyze the relationship between CTCs-HER2 and histological HER-2 expression in breast cancer patients,and to analyze the role and clinical value of the changes of CTCs in breast cancer patients before and after NAT in evaluating the efficacy of NAT.Methods: According to the inclusion and exclusion criteria,72 female patients with invasive breast cancer who were diagnosed with invasive breast cancer after core needle biopsy from September 2020 to September 2022 in the Breast and Thyroid Surgery Department of the First People’s Hospital of Yunnan Province Research.Before NAT,after every two treatment cycles,and after the treatment,8 m L of venous blood from the uninjured upper limb of the patient was drawn,and microfluidic chip technology was used to detect CTCs and CTCs-HER2 in the peripheral blood of the patient.According to the change of CTCs value before and after NAT,the decrease of CTCs value compared with before treatment was defined as effective,and the value of CTCs increased or remained unchanged compared with before treatment was defined as ineffective.Use Response Evaluation Criteria in Solid Tumors(RECIST)to evaluate the efficacy of patients after every two treatment cycles,and continue treatment for patients with complete remission(CR),partial remission(PR)and stable disease(SD)until the completion of 6 cycles Periodic treatment,while those with progressive disease(PD)will be replaced with treatment or undergo surgery.The curative effect of NAT was evaluated based on pathology(Miller-Payne grading system),and statistical principles were used to analyze the relationship between the detection of CTCs before NAT and the clinicopathological characteristics of the primary tumor,the changes of CTCs before and after NAT,and the curative effect of patients The relationship between CTCs-HER2 detection before and after NAT was compared with the histological HER-2 status of patients,and the consistency analysis between CTCs detection and pathological evaluation was performed by Kappa test.Results: The detection rate of CTCs in breast cancer patients before NAT was 70.8%(51/72),and The detection rate of CTCs in peripheral blood was higher in patients with late TNM stage,positive axillary lymph nodes,positive HER-2 and high expression of Ki67(≥15%)(P<0.05).However,the detection of CTCs was not related to the patient’s age,menopausal status,BMI,tumor size,hormone receptor expression and molecular typing(P>0.05).The positive rate of CTCs-HER2 after NAT was 33.3%(24/72),which showed a significant decrease(P<0.05)compared to55.6%(40/72)before NAT.The consistency between CTCs-HER2 before NAT and histological HER-2 was moderate(Kappa=0.483,P<0.001),while the consistency between CTCs HER2 after NAT and histological HER-2 was moderate(Kappa=0.505,P <0.001).,and the value of CTCs was also significantly lower after NAT(Z=-3.276,P<0.001).After NAT,the positive rate of CTCs-HER2 was 33.3%(24/72),which was partially decreased compared with 55.6%(40/72)before NAT(P<0.05).The changes of CTCs before and after NAT were compared with the positive-positive and positive-negative data of patients in the two groups,and the efficacy of NAT was evaluated by pathology.There was a significant difference in the efficacy of the two groups(χ~2=6.594,P<0.05).The changes of CTCs before and after NAT were negative-negative and negative-positive.The data of the two groups were compared,and there was no correlation between the efficacy of the two groups(χ~2=4.667,P>0.05).The correlation analysis between the decrease of CTCs count before and after NAT and the patient’s MP grade showed a positive correlation(r=0.629,P<0.001).The consistency of the two methods of CTCs detection and pathological evaluation was moderately consistent(Kappa=0.477,P<0.001).The sensitivity of CTCs detection to evaluate the efficacy of NAT was 72%(36/50),the specificity was 81.8%(18/22),the misdiagnosis rate was 18.2%(4/22),and the missed diagnosis rate was 28%(14/50),with an accuracy of 75%(54/72).Conclusion(s):1.The detection of CTCs was related to TNM stage,Ki67 level,axillary lymph node and HER-2 expression status of breast cancer patients.The invasive breast cancer patients with late stage,high expression of Ki67,positive axillary lymph nodes and positive HER-2 had higher detection rate of CTCs.2.After NAT,the levels of CTCs and CTCs-HER2 in peripheral blood decreased significantly,and the consistency between CTCs-HER2 state and tissue HER-2state was high before and after NAT.The changes of CTCs before and after NAT can reflect the curative effect of treatment to some extent.3.The detection of CTCs and CTCs-HER2 can be used as a new method to evaluate the efficacy of NAT in breast cancer patients.It is recommended to dynamically monitor CTCs and CTCs-HER2 to assist clinical individualized treatment of patients.