A Study Of Risk Assessment For Recurrence Of HER2-Positive Breast Cancer And Changes In Tumor Immune Microenvironment During The Course Of Targeted Therapy

Background: Breast cancer has surpassed lung cancer as the most common cancer in the world.Breast cancer is a solid tumor with high heterogeneity,of which HER2-positive type accounts for 15-20% of the total population.Although most of the patients are cured in the 1-year program of targeted therapy,1/4 of the patients still face the recurrence or death of breast cancer within 10 years,and the prognosis of patients once recurrence is poor.Therefore,how to accurately assess the recurrence risk of patients in the early stage,screen out the high-risk groups of recurrence and metastasis and carry out targeted stepped-step treatment has become an urgent problem to be solved.Tumor immune microenvironment refers to an environment composed of all kinds of immune cells and immunologically active substance in which tumor cells live.Tumor-infiltrating lymphocytes(TILs),macrophages and neutrophils are the main immune cells in the microenvironment.Programmed cell death 1(PD-1)/Programmed cell death-ligand 1(PD-L1)is considered to be an important pathway for the immune escape of tumor cells.The change of immune microenvironment plays an important role in the recurrence and metastasis of breast cancer patients and PD-L1 positive has also been shown to be sensitive to immunotherapy.Currently,more studies focus on triple-negative breast cancer,and few studies on HER2-positive breast cancer,mostly focusing on neoadjuvant fields.There is no study on the role of immune microenvironment in the disease progression of HER2-positive breast cancer patients.So we design this topic.Objective: This study was to retrospectively analyze all patients with early HER2-positive breast cancer admitted to our hospital,to explore the risk factors affecting the recurrence risk of patients with early HER2-positive breast cancer,and to build a prediction model.The characteristics of the immune microenvironment of the recurrent and primary foci in patients with HE2-positive breast cancer were observed by immunohistochemistry to summarize the changes and possible mechanisms of the immune microenvironment in the course of disease progression,so as to provide a basis for the clinical evaluation and the selection of immunotherapy for patients with HER2-positive breast cancer.Results:In the first part,a total of 817 patients who met the standards were found,522 patients received targeted therapy,and the other 289 patients didn’t.1.Targeted therapy can significantly prolonged the DFS(HR:0.62,95CI% : 0.43-0.90,P=0.011)of patients.2.Age at onset(≥45 vs < 45,HR:0.68,95%CI:0.45-0.93,P=0.0494),histological grade(II vs I,HR:0.68,95%CI:0.08-0.95,P=0.0411;III vs I HR:0.35,95%CI:0.08-0.95,P=0.0411),hormone receptor expression(positive vs negative,HR:0.65,95%CI:0.44-0.96,P= 0.0289),fertility(yes vs no,HR:0.35,95%CI:0.12-0.98,P=0.0462),targeted therapy(yes vs no,HR:0.57,95%CI:0.38-0.86,P=0.007),and carcinoembryonic antigen(CEA)(high vs normal,HR:2.04,95%CI:1.36-3.01,P=0.0003)was an independent risk factor for prognosis in patients with HER2-positive breast cancer.In the second part,a total of 27 recurrent patients were included,including 16 patients who received targeted therapy and 11 patients who did not receive targeted therapy.According to the statistics:3.In patients with high recurrence risk of HER2-positive breast cancer,a large number of immune cells were infiltrated in the primary site,and the positive rate of PD-L1+TILs was 100%;4.The immune microenvironment of the recurrent foci was significantly changed compared with the primary foci.The CD4+TILs(P < 0.0001),CD20+ TILs(P < 0.0105)and PD-L1+TILs(P < 0.0007)of the recurrence foci were significantly changed in the targeted therapy group.The infiltration rate of CD8+ TILs in the untargeted treatment group was significantly decreased(P < 0.05),.There was no difference in the other subtypes of TILsConclusion:1.Targeted therapy can significantly reduce the risk of recurrence in patients with HER2-positive breast cancer;2.Patients with early HER2-positive breast cancer with negative lymph nodes and tumor size less than 2cm can try step-down therapy based on patient recurrence risk;3.Young,larger tumor size,more lymph node metastases,nonfertility,higher tumor histological grade,higher CEA,hormone receptor negative,and no postoperative targeted therapy are independent risk factors for the prognosis of HER2-positive breast cancer.4.A large number of immune cell infiltration in the tumor microenvironment suggests a high risk of recurrence in HER2-positive breast cancer patients.Targeted therapy can significantly reduces the expression of all types of immune cells and PD-L1.