ABCB1基因型对紫杉烷类药物用于乳腺癌疗效和安全性影响的Meta分析
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篇名: ABCB1基因型对紫杉烷类药物用于乳腺癌疗效和安全性影响的Meta分析
TITLE: Meta-analysis of the effects of ABCB1 genotype on the efficacy and safety of taxanes in the treatment of breast cancer
摘要: 目的 评价ABCB1基因型对紫杉烷类药物用于乳腺癌疗效和安全性的影响。方法检索Embase、Cochrane图书馆、PubMed、中国知网和万方数据,收集紫杉烷类药物用于乳腺癌的队列研究和病例-对照研究。检索时限为建库起至2023年7月。筛选文献、提取数据和评价质量后,采用RevMan5.3软件进行Meta分析。结果共纳入11项研究,共计1321例患者。3种基因型与有效率及发生骨髓抑制、神经毒性(除ABCB1C1236T等位基因和隐性基因外)、超敏反应均无关(P>0.05)。亚组分析结果显示,使用蒽环类药物+5-氟尿嘧啶+环磷酰胺+紫杉烷类药物时,ABCB1C1236T显性模型与有效率有关(P<0.05);使用紫杉烷类药物+曲妥珠单抗时,ABCB1C3435T隐性模型与有效率有关(P<0.05)。样本量≥100、使用环磷酰胺+表柔比星+5-氟尿嘧啶+紫杉醇或环磷酰胺+表柔比星+紫杉醇+曲妥珠单抗或环磷酰胺+表柔比星+5-氟尿嘧啶+曲妥珠单抗+紫杉醇方案的ABCB1C1236T等位基因模型和隐性模型以及非洲地区、样本量<100的隐性模型与发生周围神经病变,隐性模型与发生皮肤不良反应均有关(P<0.05)。样本量≥100时发生中性粒细胞计数减少与ABCB1C3435T隐性模型,样本量<100、使用多西他赛+表柔比星+环磷酰胺时发生白细胞计数减少与等位基因模型和显性模型,发生感染与显性模型均有关(P<0.05)。样本量<100时发生中性粒细胞计数减少与ABCB1G2677T/A等位基因模型,样本量≥100时发生水肿与等位基因模型和隐性模型,发生感染与等位基因模型和显性模型均有关,尤其在中性粒细胞计数伴发热患者中(P<0.05)。结论ABCB1基因型与紫杉烷类药物用于乳腺癌患者的有效率无相关性,但ABCB1C3435T与发生中性粒细胞计数减少、白细胞计数减少和感染有关,ABCB1C1236T与发生神经毒性和皮肤不良反应有关,ABCB1G2677T/A与发生中性粒细胞计数减少、感染和水肿有关。
ABSTRACT: OBJECTIVE To evaluate the effects of ABCB1 genotypes on the efficacy and safety of taxanes in the treatment of breast cancer. METHODS By searching Embase,the Cochrane Library, PubMed, CNKI, and Wanfang databases, cohort studies and case-control studies about taxanes in the treatment of breast cancer were collected from the establishment of the database to July 2023. After screeningliterature, extracting data and evaluating quality, meta-analysis was performed by using RevMan 5.3 software. RESULTS A total of 11 studies were included, involving 1 321 patients. There was no correlation between the three genotypes and effective rate, the incidence of myelosuppression, the incidence of neurotoxicity (except for the allele and recessive model of ABCB1 C1236T), and the incidence of hypersensitivity reactions (P>0.05). The subgroup analysis showed that there was a correlation between ABCB1 C1236T dominant model and effective rate when using anthracyclines+5-fluorouracil+cyclophosphamide+taxanes (P<0.05), there was a correlation between ABCB1 C3435T recessive model and effective rate when using taxanes+trastuzumab (P<0.05). ABCB1 C1236T allele model and recessive model were correlated with sample size ≥100 and using cyclophosphamide+epirubicin+5- fluorouracil+paclitaxel or cyclophosphamide+epirubicin+paclitaxel+trastuzumab or cyclophosphamide+epirubicin+5-fluorouracil+ trastuzumab+paclitaxel regimens; recessive model with sample size <100 and the African region were correlated with the incidence of peripheral neuropathy; recessive model was correlated with cutaneous adverse reactions (P<0.05). ABCB1 C3435T recessive model was correlated with the incidence of reduced neutrophil count with sample size ≥100; the incidence of white blood cell count reduction with sample size <100 and using docetaxel+epirubicin+cyclophosphamide was correlated with both the allele model and the dominant model; the incidence of infections was correlated with the dominant model (P<0.05). The incidence of neutrophil count reduction with the sample size <100 was correlated with allele model of ABCB1 G2677T/A; the incidence of edema with sample size ≥100 was correlated with allele model and recessive model; the incidence of infection was correlated with allele model and dominant model, especially in patients with neutrophil count complicated with fever (P<0.05). CONCLUSIONS ABCB1 genotypes are not correlated with effective rate of taxanes in the treatment of breast cancer, but ABCB1 C3435T genotype is associated with decreased neutrophil counts, decreased white blood cell counts and infections; ABCB1 C1236T genotype is associated with neurotoxicity and cutaneous adverse reactions; ABCB1 G2677T/A genotype is associated with decreased neutrophil counts, infections, and edema.
期刊: 2024年第35卷第10期
作者: 张恕芳;李妍;刘伦;耿晓宁;周波;张仲涛;刘富垒
AUTHORS: ZHANG Shufang,LI Yan,LIU Lun,GENG Xiaoning,ZHOU Bo,ZHANG Zhongtao,LIU Fulei
关键字: 乳腺癌;ABCB1基因型;基因多态性;紫杉醇;多西他赛;疗效;安全性
KEYWORDS: breast cancer; ABCB1 genotypes; gene polymorphism; paclitaxel; docetaxel; efficacy; safety
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