Effect Of Neoadjuvant In Combination With Chemotherapy On Tumor-infiltrating Lymphocytes And PD-L1 Expression In HER2-overexpression Breast Cancer And Its Clinical Significance

BackgroundNeoadjuvant Herceptin combined with chemotherapy can significantly improve the efficacy of HER2+ breast cancer compared with chemotherapy alone,but there are still some patients who will progress after treatment,thus affecting the follow-up treatment and prognosis.Many factors,such as tumor size,lymph node metastasis and HR expression,are correlated with the prediction of neoadjuvant therapy efficacy,but breast cancer is a heterogeneous disease.The choice of neoadjuvant therapy based on the above factors cannot benefit all patients.The rapid development of gene detection levels makes it possible to predict the expression of HER2+ neoadjuvant therapy.However,the research on detecting the expression of specific target genes in tumor tissues to predict the efficacy of neoadjuvant therapy is still in the exploratory stage.It has not been found that a widely used molecular marker can accurately and effectively predict the efficacy of neoadjuvant therapy.In HER2+ breast cancer patients,programmed death ligand-1(PD-L1)can predict different outcomes of neoadjuvant therapy for HER2+ breast cancer,and the study focuses on PD-L1 and new tissue in neoadjuvant therapy.Correlation study on the efficacy of adjuvant therapy,lack of correlation between PD-L1 expression and its expression in paired tissues before and after neoadjuvant therapy and the efficacy of neoadjuvant therapy.Similarly,tumor-infiltrating lymphocytes(TILs),which are important predictors of neoadjuvant therapy for HER2+ breast cancer,are mostly concentrated in neoadjuvant pre-treatment tissues,and there is a lack of correlation between TILs and neoadjuvant therapy in paired tissues before and after neoadjuvant therapy.This study aimed to investigate the relationship between the expression of TILs and PD-L1 and their expression changes before and after neoadjuvant therapy with the efficacy of HER2+ breast cancer neoadjuvant combined with chemotherapy.Objective1.To explore the relationship between the number and number of TILs and the clinicopathological features of HER2+ breast cancer patients and the efficacy of neoadjuvant therapy.2.To explore the relationship between the expression and expression of PD-L1 and the clinicopathological features of HER2+ breast cancer patients and the efficacy of neoadjuvant therapy.3.Explore the factors that influence p CR after neoadjuvant therapy for HER2+ breast cancer.MethodsIn this retrospective study,we included 115 identified patients with HER2-positive invasive breast cancer treated with NCT between 2004 and 2017 at Shandong Cancer Hospital.Among them,36 patients received neoadjuvant chemotherapy alone,and 79 patients received neoadjuvant chemotuzumab combined with chemotherapy.The expression of PD-L1 was detected by immunohistochemistry.Histopathological analysis of TILs was performed by HE staining in paraffin sections.The categorical variables were compared using the chi-square test for statistical differences.The continuous variables were compared with the paired t-test for statistical differences.Risk factors were analyzed by single factor and multivariate logistic regression models.The factors with p<0.15 in the univariate analysis were included in the multivariate analysis.P<0.05 was considered as the difference.Results:The expression of PD-L1 was negatively correlated with the expression of PR in breast cancer before neoadjuvant therapy(P < 0.05),and negatively correlated with the expression of ER and PR after neoadjuvant therapy(P < 0.05).Expression of PD-L1 in pathological tissues of HER2+ breast cancer before and after neoadjuvant therapy and its relationship with age and swelling.There was no significant correlation between tumor diameter,lymph node metastasis,ER,PR,Ki67 and menstrual status(P > 0.05),but there was no significant correlation between Herceptin combined with chemotherapy group and chemotherapy alone group(P > 0.05),and there was no significant correlation between Herceptin combined chemotherapy group and chemotherapy alone group(P > 0.05).The results showed that the expression of PD-L1 was positive in 28 cases(29.1%)before neoadjuvant therapy and 18 cases(18.8%)after neoadjuvant therapy in 96 non-p CR HER2+ breast cancer patients.The expression of PD-L1 in breast cancer was down-regulated after neoadjuvant therapy compared with that before neoadjuvant therapy(P ? 0.011).Among them,28 non-p CR patients who received neoadjuvant Herceptin combined chemotherapy,the expression of PD-L1 was positive in 7 cases(25%)before treatment and 5 cases(20%)after treatment.the expression of PD-L1 in breast cancer tissue was down-regulated after neoadjuvant therapy compared with that before neoadjuvant therapy(P ? 0.024).Of the 68 non-p CR patients,PD-L1 was positive in 21 cases(31.0%)before treatment and 13 cases(19.0%)after treatment.There was no significant difference in the down-regulation of PD-L1 expression in breast cancer after neoadjuvant therapy compared with that before neoadjuvant therapy(P ? 0.185).The expression of PD-L1 in breast cancer tissues was negatively correlated with the expression of PR(P<0.05).The expression of PD-L1 was negatively correlated with the expression of ER and PR after neoadjuvant therapy(P<0.05).There was no significant correlation between the expression of PD-L1 and the clinicopathological features of HER2+ breast cancer before and after neoadjuvant therapy(P>0.05).Further subgroup analysis of Herceptin combined with chemotherapy and chemotherapy alone found that 96 patients with non-p CR HER2+ breast cancer had positive PD-L1 expression before neoadjuvant therapy(28.9%),after neoadjuvant therapy PD-L1 expression was positive in 18 patients(18.8%).The high level of TILs in breast cancer tissues before neoadjuvant therapy was negatively correlated with PR expression.The expression of breast cancer in neoadjuvant breast cancer was positively correlated with menopausal status(P<0.05).The number of TILs in the tissue after neoadjuvant treatment was significantly higher than that before treatment(P<0.001).In predicting the efficacy of neoadjuvant therapy,lymph node metastasis status and pre-treatment TILs were independent predictors of p CR(HR: 14.150,95% CI: 1.647-121.553,P=0.016),(HR: 1.134,95% CI: 1.031-1.248,P = 0.01).Univariate analysis showed that age,tumor diameter,ER status,PR status,menstrual status,PD-L1 expression and its changes before and after treatment,TILs and their changes before and after treatment were not associated with chemotherapy grade(Grade 1-4)(P> 0.05).Multivariate analysis showed that there was no correlation between PD-L1 expression and its changes before and after treatment,TILs before and after treatment,and chemotherapy grade(grade 1-4)(P>0.05).Conclusion:1.In non-p CR HER2+ breast cancer patients,neoadjuvant Herceptin combined with chemotherapy may down-regulate the expression of PD-L1,but the change of PD-L1 expression before and after treatment cannot predict the efficacy of neoadjuvant therapy.Lymph node metastasis status and pre-treatment TILs were independent predictors of p CR for neoadjuvant therapy.2.In non-p CR HER2+ breast cancer patients,neoadjuvant therapy can increase the number of TILs,but elevated TILs cannot predict neoadjuvant therapy.3.Lymph node metastasis status and pre-treatment TILs are independent predictors of p CR for neoadjuvant therapy.