Version 1
: Received: 6 August 2024 / Approved: 7 August 2024 / Online: 7 August 2024 (11:35:43 CEST)
How to cite:
Miranda, C.; Galleguillos, M.; Torres, M. R.; Tardón, K.; Cáceres, D. D.; Lee, K.; Varela, N. M.; Cerpa, L. C.; Redal, M. A.; Antón, M. A.; Merabachvili, G.; Quiñones, L. A. Association Analysis among Tamoxifen Metabolites and Genetic Polymorphisms in Hormone-Dependent Chilean Breast Cancer Patients: A Preliminary Study. Preprints2024, 2024080475. https://doi.org/10.20944/preprints202408.0475.v1
Miranda, C.; Galleguillos, M.; Torres, M. R.; Tardón, K.; Cáceres, D. D.; Lee, K.; Varela, N. M.; Cerpa, L. C.; Redal, M. A.; Antón, M. A.; Merabachvili, G.; Quiñones, L. A. Association Analysis among Tamoxifen Metabolites and Genetic Polymorphisms in Hormone-Dependent Chilean Breast Cancer Patients: A Preliminary Study. Preprints 2024, 2024080475. https://doi.org/10.20944/preprints202408.0475.v1
Miranda, C.; Galleguillos, M.; Torres, M. R.; Tardón, K.; Cáceres, D. D.; Lee, K.; Varela, N. M.; Cerpa, L. C.; Redal, M. A.; Antón, M. A.; Merabachvili, G.; Quiñones, L. A. Association Analysis among Tamoxifen Metabolites and Genetic Polymorphisms in Hormone-Dependent Chilean Breast Cancer Patients: A Preliminary Study. Preprints2024, 2024080475. https://doi.org/10.20944/preprints202408.0475.v1
APA Style
Miranda, C., Galleguillos, M., Torres, M. R., Tardón, K., Cáceres, D. D., Lee, K., Varela, N. M., Cerpa, L. C., Redal, M. A., Antón, M. A., Merabachvili, G., & Quiñones, L. A. (2024). Association Analysis among Tamoxifen Metabolites and Genetic Polymorphisms in Hormone-Dependent Chilean Breast Cancer Patients: A Preliminary Study. Preprints. https://doi.org/10.20944/preprints202408.0475.v1
Chicago/Turabian Style
Miranda, C., Genevieve Merabachvili and Luis A. Quiñones. 2024 "Association Analysis among Tamoxifen Metabolites and Genetic Polymorphisms in Hormone-Dependent Chilean Breast Cancer Patients: A Preliminary Study" Preprints. https://doi.org/10.20944/preprints202408.0475.v1
Abstract
A Tamoxifen (TAM) response varies significantly among individuals due to genetic variations in cytochrome P450 2D6 (CYP2D6), as well as other TAM pharmacokinetic and/or pharmacodynamic proteins. In this study, 40 ER+ breast cancer patients who received at least 6 months of TAM treatment were prospectively recruited. The study aimed to evaluate, using HPLC-MS/MS, plasma concentrations of TAM and its metabolites, and to study the association with genetic polymorphisms (CYP2D6*4, CYP3A4*1B, CYP3A5*3, UGT2B7*2, UGT2B15*2, SULT1A1*2, and ESR1V364E) and adverse reactions. Bivariable linear regression analyses showed that CYP3A4*1/*1B is significantly associated with an increase of 4-hydroxyTAM plasmatic concentration, a decrease of endoxifen/4-hydroxyTAM ratio and the elimination of 17β estradiol. It was found that the CYP3A4*1/1B genotype alone could explain part of the variability in [4OHTAM], [endoxifen]/[4OHTAM], and 17β-estradiol plasma levels. Similarly, SULT1A1*1/*2 genotype affects the [endoxifen]/[4OHTAM] plasma ratio. Multivariable predictive models, incorporating both polymorphisms and non-genetic variables, are proposed to explain [NdesMeTAM]/[TAM], [4OHTAM]/[TAM], [endoxifen]/[NdesMeTAM], [endoxifen]/[4OHTAM], and 17β-estradiol plasma levels, as well as for predicting hot flashes and cramps. This preliminary study suggests that the genetic variants studied may influence the bioactivation and elimination of TAM, the clinically observed adverse reactions, and potentially the treatment efficacy.
Keywords
breast cancer; pharmacokinetics; pharmacodynamics; polymorphism; RAM; recurrence; tamoxifen.
Subject
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
