The Relationship Between The Expression Of TOP2A Protein And Its Different Expression Levels In Breast Cancer Tissues And The Efficacy Of Anthracycline Combined With Taxane Neoadjuvant Chemotherapy

Objective:The expression of topoisomerase Ⅱa(TOP2A)in breast cancer tissues was detected to determine the Cut-Off value of TOP2 A protein in our laboratory.To analyze the relationship between different expressions of TOP2 A protein and clinicopathological characteristics of breast cancer and pathological complete response(pCR)of neoadjuvant chemotherapy.To explore the predictive value of different expression levels of TOP2 A protein in the efficacy of anthracycline taxane neoadjuvant chemotherapy.Method:A total of 289 women with breast cancer diagnosed pathologically from January 1,2010 to November 31,2019 in Ning Xia medical university Cancer Hospital were collected.All patients underwent anthracycline combined with taxane neoadjuvant chemotherapy.The expression of topoisomerase IIa(TOP2A)was detected by immunohistochemistry(IHC),and the cut-off value of TOP2 A was obtained by statistical analysis of the receiver operating curve(ROC curve).The relationship between different expression levels of TOP2 A protein and the pathological characteristics of breast cancer and the efficacy of neoadjuvant chemotherapy was obtained using χ2 test and Logistic regression analysis.Result:1.The general cancer status and ROC curve of 289 breast cancer patients obtained the cut-off value of TOP2 A protein1.1 A total of 289 breast cancer patients were included in this study,ofwhich 55 were from 2010 to 2013,205 were from 2014 to 2017,and 29 were from2018 to 2019.The median age was 48 years(24-68 years);206 cases before menopause and 83 cases after menopause;244 cases in T1-T2 stage and 45 cases in T3-T4 stage;72 patients reached pCR and 217 patients did not reach pCR.Among them,35 patients had unknown HER-2 status,Luminal A breast cancer was28 cases,and 4 cases reached pCR;Luminal B(HER-2 positive)breast cancer was46 cases,and 13 cases reached pCR.;LuminalB(HER-2 negative)breast cancer was 101 cases,and 20 cases reached pCR;Triple negative breast cancer was 47 cases,and 20 cases reached pCR;HER-2 over-expressing breast cancer was 32 cases,and 9 cases reached pCR;35 cases of unknown molecular typing,6 cases reached pCR.1.2 The expression rate of TOP2 A protein was in the range of 0%-99%,with a median value of 30%(0%-99%)and an average value of 34%.The ROC curve was used to statistically analyze the Cut-Off value of TOP2 A protein >30%,AUC 0.636,Youden index J0.2054,sensitivity 56.94%,specificity 63.59%.According to the TOP2 A threshold of 30%,all patients were divided into two groups:TOP2A protein> 30% and TOP2 A protein expression≤ 30%,among which TOP2 A protein > 30% was 120(41.5%)cases,TOP2 A protein ≤ 30% was 169(58.5%)cases.2.Relationship between different expression levels of TOP2 A protein and clinical characteristics of breast cancerThe TOP2 A protein expression was > 30%,and the TOP2 A protein expression was ≤ 30%.Among 289 neoadjuvant chemotherapy breast cancer patients,the different expression levels of TOP2 A protein were not related to the age,menstrual status,and T stage of breast cancer patients,and there was no significant difference(P>0.05).The different expression levels of TOP2 A proteinare related to the histological grade of breast cancer patients.The higher the histological grade,the higher the proportion of TOP2 A protein > 30%,the difference is statistically significant(χ2 = 13.035,P = 0.001).3.The relationship between different expression levels of TOP2 A protein and Ki-67,ER,PR and HER-2The TOP2 A protein expression was > 30%,and the TOP2 A protein expression was ≤ 30%.Among 289 breast cancer patients with neoadjuvant chemotherapy,different expression levels of TOP2 A protein are related to the expression of ER,PR,and Ki-67.The proportion of TOP2 A protein > 30% in patients with ER-negative,PR-negative,and Ki-67 high expression is significantly higher than that of ER-positive,PR-positive,and Ki-67,and the difference was statistically significant(P < 0.01).Among them,35 breast cancer patients had unknown HER-2 status.Among 254 neoadjuvant chemotherapy breast cancer patients,different expression levels of TOP2 A protein were not related to HER-2status,and the difference was not statistically significant(P>0.05).4.Relationship between different expression levels of TOP2 A protein and molecular typing of breast cancerThe TOP2 A protein expression was > 30%,and the TOP2 A protein expression was ≤ 30%.Among 289 breast cancer patients with neoadjuvant chemotherapy,35 patients had unknown HER-2 status and molecular typing.In 254 breast cancer patients with neoadjuvant chemotherapy,different expression levels of TOP2 A protein were associated with breast cancer molecular typing.Triple negative,HER-2 over-expressing,LuminalB(HER-2-positive)breast cancer patients with TOP2 A protein > 30% higher than the proportion of patients LuminalA type and LuminalB(HER-2 negative),was statistically significant(χ2 =9.512,P = 0.049).5.The relationship between the expression of TOP2 A protein in breast cancer patients and the efficacy of anthracycline combined with taxane neoadjuvant chemotherapyAmong 289 breast cancer patients with neoadjuvant chemotherapy,72patients(24.91%)with neoadjuvant chemotherapy reached pCR and 217 patients(75.09%)with neoadjuvant chemotherapy did not reach pCR.TOP2 A protein >30% pCR significantly higher proportion of patients with TOP2 A expression ≤30% of patients,a statistically significant difference(χ2 = 9.392,P = 0.002).6.Predictive factors of anthracycline combined with taxane neoadjuvant chemotherapy for breast cancerUnivariate analysis revealed that T stage,TOP2 A,Ki-67,ER,PR,and expression were related to pCR(P<0.05).The above 5 factors were included in multivariate non-conditional logistic regression analysis(enter method),T stage(OR = 3.029,95% CI 1.123-8.169,P = 0.029)and TOP2 A protein expression>30%(OR = 0.550,95% CI 0.309-0.978,P = 0.042)is an independent predictor of pCR for breast cancer neoadjuvant chemotherapy.Conclusions: 1.According to this study,TOP2 A protein is expressed at different levels in breast cancer tissues.The optimal threshold for detection in the Department of Pathology of our hospital is 30%.Thresholds were used for analysis:TOP2A protein expression > 30% was closely related to histological grade,suggesting that TOP2 A protein expression level can reflect the ability of malignant tumors to invade.2.TOP2 A protein expression> 30% is closely related to Ki-67,ER and PR expression and breast cancer molecular typing.TOP2 A high expression is mainly concentrated in triple-negative and HER-2 positive breast cancer.The detection of TOP2 A protein expression in breast cancer can guide clinicaltreatment.3.TOP2 A protein expression > 30% is an independent predictor of the efficacy of anthracycline combined with taxane neoadjuvant chemotherapy for breast cancer.4.Through this study,the optimal threshold of TOP2 A protein expression detected by the Department of Pathology of our hospital was 30%,which will guide our hospital’s future clinical treatment of breast cancer.