共 34 条
Contribution of ABCB1 and CYP2D6 Genotypes to the Outcome of Tamoxifen Adjuvant Treatment in Premenopausal Women With Breast Cancer
被引:16
作者:

Argalacsova, S.
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h-index: 0
机构:
Charles Univ Prague, Dept Oncol, Fac Med 1, Prague, Czech Republic
Gen Teaching Hosp, Prague, Czech Republic
Charles Univ Prague, Fac Med 1, Inst Pharmacol, Prague, Czech Republic Charles Univ Prague, Dept Oncol, Fac Med 1, Prague, Czech Republic

Slanar, O.
论文数: 0 引用数: 0
h-index: 0
机构:
Gen Teaching Hosp, Prague, Czech Republic
Charles Univ Prague, Fac Med 1, Inst Pharmacol, Prague, Czech Republic
Charles Univ Prague, Fac Med 1, Inst Clin Biochem & Lab Diagnost, Prague, Czech Republic Charles Univ Prague, Dept Oncol, Fac Med 1, Prague, Czech Republic

Vitek, P.
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机构:
Charles Univ Prague, Fac Med 1, Inst Radiotherapy, Prague, Czech Republic
Hosp Na Bulovce, Prague, Czech Republic Charles Univ Prague, Dept Oncol, Fac Med 1, Prague, Czech Republic

Tesarova, P.
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机构:
Charles Univ Prague, Dept Oncol, Fac Med 1, Prague, Czech Republic
Gen Teaching Hosp, Prague, Czech Republic Charles Univ Prague, Dept Oncol, Fac Med 1, Prague, Czech Republic

Bakhouche, H.
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Gen Teaching Hosp, Prague, Czech Republic
Charles Univ Prague, Fac Med 1, Inst Pharmacol, Prague, Czech Republic Charles Univ Prague, Dept Oncol, Fac Med 1, Prague, Czech Republic

Drazdakova, M.
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h-index: 0
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Gen Teaching Hosp, Prague, Czech Republic
Charles Univ Prague, Fac Med 1, Inst Clin Biochem & Lab Diagnost, Prague, Czech Republic Charles Univ Prague, Dept Oncol, Fac Med 1, Prague, Czech Republic

Bartosova, O.
论文数: 0 引用数: 0
h-index: 0
机构:
Gen Teaching Hosp, Prague, Czech Republic
Charles Univ Prague, Fac Med 1, Inst Pharmacol, Prague, Czech Republic Charles Univ Prague, Dept Oncol, Fac Med 1, Prague, Czech Republic

Zima, T.
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h-index: 0
机构:
Gen Teaching Hosp, Prague, Czech Republic
Charles Univ Prague, Fac Med 1, Inst Clin Biochem & Lab Diagnost, Prague, Czech Republic Charles Univ Prague, Dept Oncol, Fac Med 1, Prague, Czech Republic

Pertuzelka, L.
论文数: 0 引用数: 0
h-index: 0
机构:
Charles Univ Prague, Dept Oncol, Fac Med 1, Prague, Czech Republic
Gen Teaching Hosp, Prague, Czech Republic Charles Univ Prague, Dept Oncol, Fac Med 1, Prague, Czech Republic
机构:
[1] Charles Univ Prague, Dept Oncol, Fac Med 1, Prague, Czech Republic
[2] Gen Teaching Hosp, Prague, Czech Republic
[3] Charles Univ Prague, Fac Med 1, Inst Pharmacol, Prague, Czech Republic
[4] Charles Univ Prague, Fac Med 1, Inst Clin Biochem & Lab Diagnost, Prague, Czech Republic
[5] Charles Univ Prague, Fac Med 1, Inst Radiotherapy, Prague, Czech Republic
[6] Hosp Na Bulovce, Prague, Czech Republic
关键词:
P-glycoprotein;
SNP;
Pharmacogenomics;
Tamoxifen;
CYP2D6;
SINGLE NUCLEOTIDE POLYMORPHISMS;
CYTOCHROME-P450;
2D6;
CLINICAL-OUTCOMES;
MDR1;
GENE;
PHARMACOGENETICS;
ASSOCIATION;
METABOLISM;
FREQUENCY;
SURVIVAL;
ALLELE;
D O I:
10.33549/physiolres.933234
中图分类号:
Q4 [生理学];
学科分类号:
071003 ;
摘要:
Recent pre-clinical evidence suggests that the active metabolite of tamoxifen, endoxifen, is a substrate for efflux pump P-glycoprotein. The aim of our study was to evaluate, if the polymoprhisms within ABCB1 gene alter tamoxifen adjuvant treatment efficacy in premenopausal women. Totally 71 premenopausal women with estrogen receptor positive breast cancer indicated for tamoxifen adjuvant treatment were followed retrospectively for median period of 56 months. The gentic polymorphisms of CYP2D6 and ABCB1 were analyzed and potential covariates as tumor grading, staging, age at the diagnosis, comedication, quantitative positivity of ER or PR were also evaluated. Cox proportional-hazards regression model indicated that patients carrying at least one variant allele in ABCB1 rs1045642 had significantly longer time to event survival compared to wild type subjects. Non-significant trend was noted for better treatment outcome of patients carrying at least one variant allele in the SNP rs2032582, while for the CYP2D6 polymorphism poor metabolizer phenotype resulted in worse outcome in comparison to extensive metabolizers subjects with HR of 4.04 (95 % CI 0.31-52.19). Similarly, patients using CYP2D6 inhibitors had non-significantly shorter time-to-event as compared to never users resulting in hazard ratio of 2.06 (95 % CI 0.40-10.63). ABCB1 polymorphisms may affect outcome of tamoxifen adjuvant treatment in premenopausal breast cancer patiens. This factor should be taken into account in addition to the CYP2D6 polymorphism or phenotypic inhibition of CYP2D6 activity.
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收藏
页码:S539 / S547
页数:9
相关论文
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机构: Mayo Clin & Mayo Fdn, Coll Med, Dept Oncol, Rochester, MN 55905 USA

Desta, Zeruesenay
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机构: Mayo Clin & Mayo Fdn, Coll Med, Dept Oncol, Rochester, MN 55905 USA

Nguyen, Anne
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机构: Mayo Clin & Mayo Fdn, Coll Med, Dept Oncol, Rochester, MN 55905 USA

Flockhart, David A.
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机构: Mayo Clin & Mayo Fdn, Coll Med, Dept Oncol, Rochester, MN 55905 USA

Perez, Edith A.
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Ingle, James N.
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[10]
Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes
[J].
Goetz, MP
;
Rae, JM
;
Suman, VJ
;
Safgren, SL
;
Ames, MM
;
Visscher, DW
;
Reynolds, C
;
Couch, FJ
;
Lingle, WL
;
Flockhart, DA
;
Desta, Z
;
Perez, EA
;
Ingle, JN
.
JOURNAL OF CLINICAL ONCOLOGY,
2005, 23 (36)
:9312-9318

Goetz, MP
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Rae, JM
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Suman, VJ
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Safgren, SL
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Ames, MM
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Visscher, DW
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Couch, FJ
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Lingle, WL
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Flockhart, DA
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Desta, Z
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机构: Mayo Clin Rochester, Coll Med, Dept Oncol, Rochester, MN 55905 USA

Perez, EA
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Ingle, JN
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