Evaluation of the effect of CYP2D6*3, *4,*10, and *17 polymorphisms on the pharmacokinetic of tamoxifen and its metabolites in patients with hormone-positive breast cancer.
4-Hydroxytamoxifen
CYP2D6
Endoxifen
Pharmacogenetics
Pharmacokinetics
Tamoxifen
Journal
Journal of pharmaceutical and biomedical analysis
ISSN: 1873-264X
Titre abrégé: J Pharm Biomed Anal
Pays: England
ID NLM: 8309336
Informations de publication
Date de publication:
20 Jan 2024
20 Jan 2024
Historique:
received:
02
08
2023
revised:
16
10
2023
accepted:
31
10
2023
medline:
6
12
2023
pubmed:
18
11
2023
entrez:
17
11
2023
Statut:
ppublish
Résumé
A high rate of interindividual variability in response to tamoxifen (TAM) in breast cancer patients with CYP2D6 polymorphism has been reported, which affects the patient's therapeutic outcome. The objective of this study was to investigate the pharmacogenomics of CYP2D6 genotyping in Iranian patients with breast cancer treated with adjuvant TAM. A peripheral blood sample was obtained to determine the steady-state plasma concentrations of TAM and its metabolites (Endoxifen (EN) and 4-Hydroxytamoxifen (4-OHT)) using high-performance liquid chromatography with fluorescence detection (HPLC-FLU) assay. We detected CYP2D6 * 3, * 4, * 10, and * 17 single nucleotide polymorphisms via polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. A total of 84 Iranian estrogen receptor‑positive breast cancer patients receiving the daily dose of 20 mg tamoxifen were recruited. Although a consequent decrease in the median EN and 4-OHT concentrations was observed by comparing poor or intermediate metabolizer patients with an extensive metabolizer population, this difference did not reach a significant level. The mean plasma EN concentrations in poor and intermediate metabolizers were 46.1% (95% CI, 7.4-27.8%) and 59.4% (95% CI, 11.9-37.3%) of extensive metabolizer subjects, respectively. Poor and intermediate metabolizers had the mean plasma 4-OHT concentrations that were 46.6% (95% CI, 0.9-61.7%) and 73.2% (95% CI, 2.7-93.1%) of those of subjects who were extensive metabolizer, respectively. The possible role of genotyping in Iranian patients' response to treatment may explain inter-individual differences in the plasma concentrations of active metabolites of TAM.
Sections du résumé
BACKGROUND AND OBJECTIVE
OBJECTIVE
A high rate of interindividual variability in response to tamoxifen (TAM) in breast cancer patients with CYP2D6 polymorphism has been reported, which affects the patient's therapeutic outcome. The objective of this study was to investigate the pharmacogenomics of CYP2D6 genotyping in Iranian patients with breast cancer treated with adjuvant TAM.
METHODS
METHODS
A peripheral blood sample was obtained to determine the steady-state plasma concentrations of TAM and its metabolites (Endoxifen (EN) and 4-Hydroxytamoxifen (4-OHT)) using high-performance liquid chromatography with fluorescence detection (HPLC-FLU) assay. We detected CYP2D6 * 3, * 4, * 10, and * 17 single nucleotide polymorphisms via polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method.
RESULTS
RESULTS
A total of 84 Iranian estrogen receptor‑positive breast cancer patients receiving the daily dose of 20 mg tamoxifen were recruited. Although a consequent decrease in the median EN and 4-OHT concentrations was observed by comparing poor or intermediate metabolizer patients with an extensive metabolizer population, this difference did not reach a significant level. The mean plasma EN concentrations in poor and intermediate metabolizers were 46.1% (95% CI, 7.4-27.8%) and 59.4% (95% CI, 11.9-37.3%) of extensive metabolizer subjects, respectively. Poor and intermediate metabolizers had the mean plasma 4-OHT concentrations that were 46.6% (95% CI, 0.9-61.7%) and 73.2% (95% CI, 2.7-93.1%) of those of subjects who were extensive metabolizer, respectively.
CONCLUSIONS
CONCLUSIONS
The possible role of genotyping in Iranian patients' response to treatment may explain inter-individual differences in the plasma concentrations of active metabolites of TAM.
Identifiants
pubmed: 37976989
pii: S0731-7085(23)00608-8
doi: 10.1016/j.jpba.2023.115839
pii:
doi:
Substances chimiques
Cytochrome P-450 CYP2D6
EC 1.14.14.1
Antineoplastic Agents, Hormonal
0
4-hydroxy-N-desmethyltamoxifen
46AF8680RC
afimoxifene
17197F0KYM
Tamoxifen
094ZI81Y45
Hormones
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
115839Informations de copyright
Copyright © 2023. Published by Elsevier B.V.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Amirhossein sahebkar reports financial support was provided by Mazandaran University of Medical Sciences. The authors wish to thank the staff and the patients of Tooba clinic, Mazandaran, Sari, Iran.