Detailed Information

Cited 0 time in webofscience Cited 0 time in scopus
Metadata Downloads

Variations in plasma concentrations of tamoxifen metabolites and the effects of genetic polymorphisms on tamoxifen metabolism in Korean patients with breast cancer

Authors
Woo, Hye InLee, Se KyungKim, JiyoungKim, Seok WonYu, JonghanBae, Soo YounLee, Jeong EonNam, Seok JinLee, Soo-Youn
Issue Date
21-11월-2017
Publisher
IMPACT JOURNALS LLC
Keywords
tamoxifen; metabolite; drug monitoring; genotype; variation
Citation
ONCOTARGET, v.8, no.59, pp.100296 - 100311
Indexed
SCIE
SCOPUS
Journal Title
ONCOTARGET
Volume
8
Number
59
Start Page
100296
End Page
100311
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/81522
DOI
10.18632/oncotarget.22220
ISSN
1949-2553
Abstract
Inter-individual variation in tamoxifen metabolism in breast cancer patients is caused by various genetic and clinical factors. We measured the plasma concentrations of tamoxifen and its metabolites and investigated genetic polymorphisms influencing those concentrations. We measured the concentrations of tamoxifen, endoxifen, N-desmethyltamoxifen (NDM), and 4-hydroxytamoxifen (4-OH tamoxifen) in 550 plasma specimens from 281 breast cancer patients treated with tamoxifen. Duplicate or triplicate specimens were obtained from 179 patients at 3-month intervals. In 80 patients, genotyping for tamoxifen metabolizing enzymes was performed using the DMET Plus array and long-range PCR. Plasma concentrations of tamoxifen and its metabolites showed wide variations among patients. The following genetic polymorphisms were associated with the plasma concentrations when body mass index and tamoxifen concentrations were considered as co-variables: CYP1A2 -2467delT, CYP2B6 genotype, CYP2D6 activity score (AS), and FMO3 441C > T. CYP2D6 AS and three variants in the SULT1E1 gene showed correlation with ratios of tamoxifen metabolites. CYP2D6 AS was the only variable that showed associations with both metabolite concentration and ratio: endoxifen (P < 0.001), NDM (P < 0.001), endoxifen/NDM (P < 0.001), NDM/tamoxifen (P < 0.001), and 4-OH tamoxifen/tamoxifen (P = 0.005). Serial measurements of 448 plasma concentrations in 179 patients at 3-month intervals showed wide intra-individual variation. Our study showed that genetic polymorphisms can in part determine the baseline concentrations of tamoxifen and its metabolites. However, marked intra-individual variations during follow-up monitoring were observed, and this could not beexplained by genotype. Therefore, serial measurements of tamoxifen and its metabolites would be helpful in monitoring in vivo tamoxifen metabolic status.
Files in This Item
There are no files associated with this item.
Appears in
Collections
College of Medicine > Department of Medical Science > 1. Journal Articles

qrcode

Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.

Altmetrics

Total Views & Downloads

BROWSE