Meta-analysis of the effects of <italic style="font-style: italic">ABCB1</italic> genotype on the efficacy and safety of taxanes in the treatment of breast cancer

ZHANG Shufang; LI Yan; LIU Lun; GENG Xiaoning; ZHOU Bo; ZHANG Zhongtao; LIU Fulei

doi:10.6039/j.issn.1001-0408.2024.10.18

您当前的位置：

首页 >

文章列表页 >

Meta-analysis of the effects of ABCB1 genotype on the efficacy and safety of taxanes in the treatment of breast cancer

更新时间：2025-09-25

- Meta-analysis of the effects of ABCB1 genotype on the efficacy and safety of taxanes in the treatment of breast cancer
- ZHONGGUO YAOFANG Vol. 35, Issue 10, Pages: 1254-1259(2024)
- 作者机构：
  
  1.青岛大学附属泰安市中心医院药学部，山东泰安　271099
  2.山东第一医科大学第一附属医院（山东省千佛山医院）临床药学科，济南　250014
  3.青岛大学附属泰安市中心医院博士后工作站，山东泰安　271099
  4.青岛大学附属泰安市中心医院肿瘤精确干预与转化医学实验室，山东泰安　271099
  5.青岛大学附属泰安市中心医院科研科，山东泰安　271099
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2024.10.18
  CLC： R969
- Received：03 November 2023，
  
  Revised：2024-04-24，
  
  Accepted：28 April 2024，
  
  Published：30 May 2024
- 稿件说明：
移动端阅览
张恕芳,李妍,刘伦,等.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[J].中国药房,2024,35(10):1254-1259.

ZHANG Shufang,LI Yan,LIU Lun,et al.Meta-analysis of the effects of ABCB1 genotype on the efficacy and safety of taxanes in the treatment of breast cancer[J].ZHONGGUO YAOFANG,2024,35(10):1254-1259.
张恕芳,李妍,刘伦,等.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[J].中国药房,2024,35(10):1254-1259. DOI： 10.6039/j.issn.1001-0408.2024.10.18.

ZHANG Shufang,LI Yan,LIU Lun,et al.Meta-analysis of the effects of ABCB1 genotype on the efficacy and safety of taxanes in the treatment of breast cancer[J].ZHONGGUO YAOFANG,2024,35(10):1254-1259. DOI： 10.6039/j.issn.1001-0408.2024.10.18.

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RevMan 5.3软件进行Meta分析。

结果

共纳入11项研究，共计1 321例患者。3种基因型与有效率及发生骨髓抑制、神经毒性（除

ABCB1

C1236T等位基因和隐性基因外）、超敏反应均无关（

＞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，

ABCB1

C1236T显性模型与有效率有关（

＜0.05）；使用紫杉烷类药物+曲妥珠单抗时，

ABCB1

C3435T隐性模型与有效率有关（

＜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

ABCB1

C1236T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（

＜0.05）。样本量≥100时发生中性粒细胞计数减少与

ABCB1

C3435T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（

＜0.05）。样本量＜100时发生中性粒细胞计数减少与

ABCB1

G2677T/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（

＜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

ABCB1

C3435T与发生中性粒细胞计数减少、白细胞计数减少和感染有关，

ABCB1

C1236T与发生神经毒性和皮肤不良反应有关，

ABCB1

G2677T/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 screening literature， 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 （

＞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 （

＜0.05）， there was a correlation between

ABCB1

C3435T recessive model and effective rate when using taxanes+trastuzumab （

＜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 （

＜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 （

＜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 （

＜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.

关键词

Keywords

references

XIA C F ， DONG X S ， LI H ， et al . Cancer statistics in China and the United States，2022：profiles，trends，and determinants [J ] . Chin Med J ， 2022 ， 135 （ 5 ）： 584 - 590 .

GUIJOSA A ， FREYRIA A ， ESPINOSA-FERNANDEZ J R ， et al . Pharmacogenetics of taxane-induced neuroto-xicity in breast cancer：systematic review and meta-analysis [J ] . Clin Transl Sci ， 2022 ， 15 （ 10 ）： 2403 - 2436 .

TULSYAN S ， CHATURVEDI P ， SINGH A K ， et al . Assessment of clinical outcomes in breast cancer patients treated with taxanes：multi-analytical approach [J ] . Gene ， 2014 ， 543 （ 1 ）： 69 - 75 .

PRIYADARSHINI R ， RAJ G M ， KAYAL S ， et al . Influence of ABCB1 C3435T and C1236T gene polymorphisms on tumour response to docetaxel-based neo-adjuvant chemotherapy in locally advanced breast cancer patients of South India [J ] . J Clin Pharm Ther ， 2019 ， 44 （ 2 ）： 188 - 196 .

JI M H ， TANG J H ， ZHAO J H ， et al . Polymorphisms in genes involved in drug detoxification and clinical outcomes of anthracycline-based neoadjuvant chemotherapy in Chinese Han breast cancer patients [J ] . Cancer Biol Ther ， 2012 ， 13 （ 5 ）： 264 - 271 .

CHOI J R ， KIM J O ， KANG D R ， et al . Genetic variations of drug transporters can influence on drug response in patients treated with docetaxel chemotherapy [J ] . Cancer Res Treat ， 2015 ， 47 （ 3 ）： 509 - 517 .

TULSYAN S ， MITTAL R D ， MITTAL B . The effect of ABCB1 polymorphisms on the outcome of breast cancer treatment [J ] . Pharmgenomics Pers Med ， 2016 ， 9 ： 47 - 58 .

ANGELINI S ， BOTTICELLI A ， ONESTI C E ， et al . Pharmacogenetic approach to toxicity in breast cancer patients treated with taxanes [J ] . Anticancer Res ， 2017 ， 37 （ 5 ）： 2633 - 2639 .

KIM H J ， IM S A ， KEAM B ， et al . ABCB1 polymorphism as prognostic factor in breast cancer patients treated with docetaxel and doxorubicin neoadjuvant chemotherapy [J ] . Cancer Sci ， 2015 ， 106 （ 1 ）： 86 - 93 .

STANG A . Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses [J ] . Eur J Epidemiol ， 2010 ， 25 （ 9 ）： 603 - 605 .

CHANG H ， RHA S Y ， JEUNG H C ， et al . Association of the ABCB1 gene polymorphisms 2677G＞T/A and 3435C＞T with clinical outcomes of paclitaxel monotherapy in metastatic breast cancer patients [J ] . Ann Oncol ， 2009 ， 20 （ 2 ）： 272 - 277 .

KIM J W ， KIM J H ， IM S A ， et al . ABCB1，FCGR2A，and FCGR3A polymorphisms in patients with HER2-positive metastatic breast cancer who were treated with first-line taxane plus trastuzumab chemotherapy [J ] . Oncology ， 2012 ， 83 （ 4 ）： 218 - 227 .

刘新兰，张海霞，赵岳阳，等 . ABCB1基因多态性对乳腺癌紫杉类药物化疗疗效的影响 [J ] . 西安交通大学学报（医学版）， 2016 ， 37 （ 3 ）： 383 - 387 .

LIU X L ， ZHANG H X ， ZHAO Y Y ， et al . Influence of ABCB1 gene polymorphisms on breast cancer with paclitaxel-based chemotherapy [J ] . J Xi’an Jiaotong Univ Med Sci ， 2016 ， 37 （ 3 ）： 383 - 387 .

李倩，王西勇 . ABCB1基因多态性对乳腺癌化疗所致血液学毒性的影响观察 [J ] . 现代科学仪器， 2022 ， 39 （ 2 ）： 134 - 138 .

LI Q ， WANG X Y . Effect of ABCB1 gene polymorphism on hematological toxicity in breast cancer patients receiving paclitaxel chemotherapy [J ] . Mod Sci Instrum ， 2022 ， 39 （ 2 ）： 134 - 138 .

TANABE Y ， SHIMIZU C ， HAMADA A ， et al . Paclitaxel-induced sensory peripheral neuropathy is associated with an ABCB1 single nucleotide polymorphism and older age in Japanese [J ] . Cancer Chemother Pharmacol ， 2017 ， 79 （ 6 ）： 1179 - 1186 .

TSAI S M ， LIN C Y ， WU S H ， et al . Side effects after docetaxel treatment in Taiwanese breast cancer patients with CYP3A4，CYP3A5，and ABCB1 gene polymorphisms [J ] . Clin Chim Acta ， 2009 ， 404 （ 2 ）： 160 - 165 .

ECKHOFF L ， FEDDERSEN S ， KNOOP A S ， et al . Docetaxel-induced neuropathy：a pharmacogenetic case-control study of 150 women with early-stage breast cancer [J ] . Acta Oncol ， 2015 ， 54 （ 4 ）： 530 - 537 .

ABDELFATTAH N M ， SOLAYMAN M H ， ELNAHASS Y ， et al . ABCB1 single nucleotide polymorphism genotypes as predictors of paclitaxel-induced peripheral neuropathy in breast cancer [J ] . Genet Test Mol Biomarkers ， 2021 ， 25 （ 7 ）： 471 - 477 .

KIM K P ， AHN J H ， KIM S B ， et al . Prospective evaluation of the drug-metabolizing enzyme polymorphisms and toxicity profile of docetaxel in Korean patients with operable lymph node-positive breast cancer receiving adjuvant chemotherapy [J ] . Cancer Chemother Pharmacol ， 2012 ， 69 （ 5 ）： 1221 - 1227 .

DEMURTAS S ， VERDE N L ， ROTA S ， et al . Single nucleotide polymorphisms to predict taxanes toxicities and effectiveness in cancer patients [J ] . Pharmacogeno-mics J ， 2021 ， 21 （ 4 ）： 491 - 497 .

JABIR R S ， NAIDU R ， ANNUAR M A ， et al . Pharmacogenetics of taxanes：impact of gene polymorphisms of drug transporters on pharmacokinetics and toxicity [J ] . Pharmacogenomics ， 2012 ， 13 （ 16 ）： 1979 - 1988 .

CHEN Q Y ， LIN W L ， YANG J H ， et al . Prognostic value of two polymorphisms，rs1045642 and rs1128503，in ABCB1 following taxane-based chemotherapy：a meta-analysis [J ] . Asian Pac J Cancer Prev ， 2021 ， 22 （ 1 ）： 3 - 10 .

TAMBURIN S ， PARK S B ， ALBERTI P ， et al . Taxane and epothilone-induced peripheral neurotoxicity：from pathogenesis to treatment [J ] . J Peripher Nerv Syst ， 2019 ， 24 （ Suppl. 2 ）： S40 - S51 .

YAN M R ， FAN X Y ， SI H ， et al . Association between gene polymorphism and adverse effects in cancer patients receiving docetaxel treatment：a meta-analysis [J ] . Cancer Chemother Pharmacol ， 2022 ， 89 （ 2 ）： 173 - 181 .

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Efficacy and safety of ruxolitinib in the treatment of myelofibrosis

Clinical observation of doxycycline in the treatment of macrolide-unresponsive Mycoplasma pneumoniae pneumonia in children under 8 years of age

Meta-analysis of the efficacy and safety of PD-1/PD-L1 inhibitors combined with bevacizumab in the treatment of advanced non-small cell lung cancer

Clinical observation of vonoprazan-based triple therapy in treatment-naive patients with Helicobacter pylori infection

Comparison of the efficacy and safety between the drug winning the bidding for centralized procurement and the original drug of ticagrelor in acute coronary syndrome patients after percutaneous coronary intervention

Related Author

WANG Wanwan

YE Jun

CHENG Hai

YAO Wei

LIU Guiling

ZHENG Jishan

CHEN Yanyan

LI Shanshan

Related Institution

Dept. of Hematology， the Third People’s Hospital of Bengbu

Dept. of Hematology， the Affiliated Hospital of Xuzhou Medical University

Dept. of Pharmacy， Women and Children’s Hospital Affiliated to Ningbo University

Dept. of Paediatrics， Women and Children’s Hospital Affiliated to Ningbo University

Dept. of Pharmacy， the Affiliated Hospital of Zunyi Medical University

⁰

Meta-analysis of the effects of ABCB1 genotype on the efficacy and safety of taxanes in the treatment of breast cancer

DOI：10.6039/j.issn.1001-0408.2024.10.18

摘要

Abstract

关键词

Keywords

references