An Observational Study Of Immune Function Status In Patients With HER-2 Positive Early Breast Cancer Treated With Chemotherapy Combined With Trastuzumab

BackgroundHER-2-positive breast cancer accounts for about 20-30%of breast cancer.Chemotherapy combined with trastuzumab is currently the standard anti-tumor treatment for HER-2-positive early-stage or metastatic breast cancer patients.Traditionally,people believe that chemotherapy has different degrees of inhibition effect on immunity.However,in recent years,more and more evidence supports the double effect of chemotherapy on inhibition as well as regulation of immunity.In addition,trastuzumab exerts anti-tumor and immune function by interacting with the immune system.The immunological mechanisms by which trastuzumab treats HER-2-positive tumors primarily include the following two ways:one is to directly block the extracellular domain of epidermal growth factor 2,block the HER-2 signaling pathway,and inhibit the growth of tumor cells;the other is Antibody-dependent cell-mediated cytotoxicity(ADCC)activates an immune response against HER-2 overexpressing cells and exerts an anti-tumor effect.Tumor immunity plays an important role in tumorigenesis,development and treatment,but the effects of different regimens of chemotherapy combined with trastuzumab on immune function in patients with breast cancer have rarely been reported.This article aims to monitor the changes of peripheral blood lymphocyte subsets and related immune factors in breast cancer patients treated with different chemotherapy regimens combined with trastuzumab.And it will accumulate clinical experience and relevant theoretical basis for the combination of chemotherapy and anti-Her-2 treatment with the body's immune function,so as to improve the therapeutic effect of HER-2 positive breast cancer treatment in the future.MethodsWe prospectively observed HER-2-positive breast cancer patients who received adjuvant therapy in the Department of Chemotherapy,Qilu Hospital Cancer Center,Shandong University from January 2016 to November 2017.The inclusion criteria are as followed:1.Histopathology confirmed breast cancer,Her-2 positive confirmed by immunohistochemistry or FISH test,regardless of hormone receptor ER,PR positive or negative;2.Application of trastuzumab treatment;3.Except for surgery,The patients have not received radiation therapy,other medical treatment,etc.All enrolled patients were divided into two groups according to the treatment plan.epirubicin +cyclophosphamide?docetaxel + trastuzumab(EC-TH)group of patients selected three treatment time nodes:baseline(A),After 4-cycle anthracycline treatment before application of trastuzumab(B),after 4 cycles of trastuzumab(C),three treatment time nodes;docetaxel + carboplatin + trastuzumab(TCH)regimen Patients in the group were selected for baseline(D),trastuzumab was used after 2 cycles(E),and trastuzumab was used after 4 cycles(F)as three time nodes.Drew peripheral venous blood separately,and detected the following indicators:lymphocyte subsets and related cytokines such as IL-6,IL-8,TNF-?.IL-2,INF-?.etc.Record the basic clinical information such as patient's age,BMI,hormone receptor status,lymph node metastasis,and vascular tumor thrombus;and statistical analysis was performed using IBM(?)SPSS(?)Statistics version 20.The outcome of P value<0.05 was considered statistically significant.ResultsA total of 50 patients with HER-2 positive breast cancer adjuvant therapy were enrolled,9 patients interrupted treatment,and the remaining 41 breast cancer patients all received trastuzumab and chemotherapy.In the 41 patients included in the analysis,29(71%)patients received chemotherapy with an anthracycline-containing EC-TH regimen therapy,and 12(29%)patients received an anthracycline-free regimen,which was chemotherapy with TCH regimen,tatistical analysis showed that:EC-TH regimen,after 4-cycle EC regimen treatment(B)compared with baseline level(A):TH cell subsets,TH/TC ratio,and B-cell levels were reduced in T lymphocyte subsets and Statistically significant(P value<0.05,Table 2);EC sequential 4-cycle TH regimen treatment(C)compared with 4-cycle EC regimen after TH regimen treatment(B):elevated TC and NK cell levels The IFN-y level was reduced,and the results were statistically significant(P value<0.05,Table 2 Table 3);EC sequential 4-cycle TH regimen treatment(C)compared with baseline(A):TH/TC ratio and B-cell levels were lowered,NK cell levels were elevated,and the results were statistically significant(P<0.05,Table 4)TCH regimen,4 cycles of TCH regimen chemotherapy(F)compared to baseline(D):TH/TC Proportion and B cell levels were decreased,while IL-6 levels were elevated,and the results were statistically significant(P value<0.05,Table 2 Table 3).Conclusion1.In the EC-TH regimen,the immune function of the patient after EC treatment is inhibited,suggesting that the chemotherapy drug inhibits the immune function of the body.2.In the EC-TH regimen,the immune function of the sequential 4-cycle TH treatment did not decrease significantly,but increased to some extent.It provides an immune basis for trastuzumab to exert anti-tumor immunity such as ADCC.3.In the TCH regimen,there was no significant change in the immune function of the body after treatment,suggesting that the immune function was stable during the treatment of TCH,providing a stable immune environment for anti-tumor treatment.4.The elevated IL-6 level after treatment with the TCH regimen may suggest that the patient's response to treatment is weak and may have a poor prognosis.The decrease of IL-6 level after EC-TH treatment may suggest that these patients have a better therapeutic response and long-term prognosis.From the perspective of cytokine anti-tumor immunity,EC-TH regimen seems to have more advantages than TCH regimen.5.In the EC-TH regimen,IFN-y levels were decreased after sequential 4-cycle TH treatment,suggesting that trastuzumab may have a negative effect on IFN-y,and that IFN-y may be used in the presence of trastuzumab,possibly increase the efficacy of trastuzumab.6.Inflammatory cytokines such as IL-2,IL-8,TNF-? do not change significantly in clinical treatment.The complex role of cytokines in the immune system is affected by many aspects.The independent effect of a cytokine does not seem to have much Correlation.