细胞色素P450酶基因多态性与复发转移性乳腺癌疗效的相关性  

Association of cytochrome P450 gene polymorphisms with efficacy in recurrent and metastatic breast cancer

作　　者：何旻[1] 巢琳[1] 华亦汇 HE Min;CHAO Lin;HUA Yi-hui(Thyroid and Breast Surgery Department,Wuxi Second People's Hospital,Wuxi 214000,Jiangsu Province,China)

机构地区：[1]无锡市第二人民医院甲乳外科,江苏无锡214000

出　　处：《中国临床药理学杂志》2024年第9期1252-1256,共5页The Chinese Journal of Clinical Pharmacology

基　　金：江苏省自然科学基金资助项目(BK20201172)。

摘　　要：目的观察细胞色素P450(CYP450)相关基因多态性对他莫昔芬(TAM)精准治疗复发转移性乳腺癌的指导价值。方法回顾性选取接受治疗的复发转移性乳腺癌患者为研究对象,所有患者均接受口服TAM治疗,将完全缓解及部分缓解的患者纳入敏感组,稳定及进展的患者纳入耐药组。通过门诊及电话对患者进行随访,截止时间为2022年12月,记录中位生存时间。比较敏感组、耐药组CYP2D6*10基因型分布、一般情况及临床病理特征。用COX比例风险回归模型并绘制Kaplan-Meier曲线分析CYP2D6*10基因型分布与TAM治疗复发转移性乳腺癌临床疗效的相关性。结果截至随访日期,CYP2D6*10基因型C/C+C/T患者(58例)的中位生存时间为18个月(95%CI:14.48~21.52),CYP2D6*10基因型TT患者(34例)的中位生存时间为13个月(95%CI:10.69~15.31)。CYP2D6*10基因型C/C+C/T患者生存率高于CYP2D6*10基因型TT患者,Log-rank检验显示,Kaplan-Meier曲线差异有统计学意义(χ^(2)=6.901,P<0.05)。与敏感组比较,耐药组中CYP2D6*10野生型C/C基因型构成比降低,突变纯合子型T/T基因型构成比升高(均P<0.05);2组CYP2D6*10突变杂合子型C/T基因型构成比比较,在统计学上差异无统计学意义(P>0.05)。与敏感组比较,耐药组原发肿瘤大小>5 cm、淋巴结转移数量≥4个、雌激素受体阳性、孕激素受体阳性及CYP2D6*10基因型分布T/T基因型构成比升高(P<0.05)。COX比例风险回归模型显示,原发肿瘤大小、淋巴结转移数量、雌激素受体情况、孕激素受体情况及CYP2D6*10基因型分布均是TAM治疗复发转移性乳腺癌临床疗效的独立预测指标(P<0.05)。结论CYP2D6*10基因多态性与TAM治疗复发转移性乳腺癌的临床疗效及中位生存期具有密切关联。Objective To observe the guiding value of cytochrome P450(CYP450)enzyme related gene polymorphism for tamoxifen(TAM)in the precise treatment of relapsed metastatic breast cancer.Methods Patients with recurrent metastatic breast cancer were selected,all of whom were treated with oral TAM,and complete remission and partial remission were included in the sensitive group,while stable and progressive were included in the drug-resistant group.Patients were followed up by outpatient and telephone visits until December 2022,and median survival time was recorded.CYP2D6*10 genotype distribution,general situation,clinicopathological characteristics of sensitive group and drug-resistant group were compared.COX proportional risk regression model was used and Kaplan-Meier curve was drawn to analyze the relationship betweenCYP2D6*10 genotype distribution and clinical efficacy of TAM in the treatment of recurrent and metastatic breast cancer.Results As of the date of follow-up,the median survival time of patients withCYP2D6*10 genotype C/C+C/T(58 patients)was 18 months(95%CI:14.48-21.52)and that of patients withCYP2D6*10 genotype TT(34 patients)was 13 months(95%CI:10.69-15.31).The survival rate of CYP2D6*10 genotype C/C+C/T patients was higher than that ofCYP2D6*10 genotype TT patients,the Log-rank test showed that the difference in Kaplan-Meier curves was statistically significant(χ^(2)=6.901,P<0.05).Compared with the sensitive group,theCYP2D6*10 wild-type C/C genotype component ratio decreased,while the mutant homozygous T/T genotype component ratio increased in the drug-resistant group(P<0.05).There was no significant difference inCYP2D6*10 heterozygote C/T genotype composition between the two groups(P>0.05).Compared with sensitive group,the size of primary tumor>5 cm,number of lymph node metastasis≥4,estrogen receptor positive,progesterone receptor positive,CYP2D6*10 genotype distribution T/T genotype composition ratio were increased in drug-resistant group(P<0.05).COX proportional risk regression model showed that primar

关 键 词：他莫昔芬 复发转移性乳腺癌 细胞色素P450酶 基因多态性 

分 类 号：R97[医药卫生—药品]