| Objective:ERCC1,RRM1,TUBB3,TYMS and TOP2A genes have been shown to be associated with drug resistance in various types of tumors;however,their roles in breast cancer chemotherapy have not been fully validated.And the aim of the present study was to evaluate the guiding significance of the above genes expression in the selection of individualized chemotherapy regimen for breast cancer.Methods:In the present study,140 well-matched patients with breast cancer,comprising 70 patients receiving individualized chemotherapy and 70receiving classic chemotherapy,were analyzed.In the individualized chemotherapy group,the m RNA expression levels of ERCC1,RRM1,TUBB3,TYMS and TOP2A in breast cancer tissues were measured using multiplex branched DNA liquidchip technology prior to chemotherapy;an individualized chemotherapy regimen was developed for each patient according to the results.As a control,patients in the classic chemotherapy group received a docetaxel+epirubicin+cyclophosphamide regimen.Survival analyses were performed using the Kaplan-Meier method.The prognostic factors for disease-free survival(DFS)and overall survival(OS)in the patients were identified via Cox’s proportional hazards regression model.Adverse reactions were evaluated according to the National Cancer Institute Common Toxicity Criteria 4.0.Results:Low expression levels of ERCC1 and RRM1 were observed in45.7 and 64.3%of the individualized chemotherapy group,respectively,while low expression levels of TUBB3 and TYMS were observed in 24.3 and 21.4%of the individualized chemotherapy group,respectively.A high expression level of TOP2A was observed in 17.1%of the individualized chemotherapy group.ERCC1 was relatively higher expressed in the patients with positivity for ER(P=0.015)and PR(P=0.005),negativity for HER-2(P=0.009)and Ki-67≤14%(P=0.017);TUBB3 was relatively higher expressed in the patients with high histological grade(P=0.042),negativity for PR(P=0.035);TYMS was relatively higher expressed in the patients with BMI≥24 kg/m~2(P=0.017),negativity for ER(P=0.035),triple negative breast cancer(P=0.031);TOP2A was relatively higher expressed in the patients with premenopausal status(P=0.022)and Ki-67>14%(P=0.021).The median follow-up time was 67.5months(1.0–84.0 months).Compared with the classic chemotherapy group,the DFS and OS of the individualized chemotherapy group were significantly longer(DFS,77.4 vs.67.1 months,P=0.039;OS,81.4 vs.75.4 months,P=0.031),and the incidence of grade 2 or 3 palpitations and chest tightness was lower(12.9 vs.27.1%,P=0.035).The chemotherapy strategy guided by genetic detection was an independent protection factor for DFS[hazard ratio(HR)=0.389,95%confidence interval(CI):0.153,0.989,P=0.047],but not an independent protection factor for OS(HR=0.340,95%CI:0.107,1.078,P=0.067).Metastasis of axillary lymph nodes was an independent risk factor for DFS(HR=7.049,95%CI:1.813,27.410,P=0.005).Additionally,the independent risk factor affected DFS(HR=3.378,95%CI:1.074,10.624,P=0.037)and OS(HR=8.140,95%CI:1.666,39.759,P=0.010)was poor endocrine therapy compliance.Conclusion:Combined detection of ERCC1,RRM1,TUBB3,TYMS and TOP2A gene expression and use of the results to guide individualized chemotherapy can improve treatment efficacy and reduce unnecessary toxicity. |
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