Predictive modeling of adverse drug reactions to tamoxifen therapy for breast cancer on base of pharmacogenomic testing

Ekaterina Olegovna Golubenko; Marina Ivanovna Savelyeva; Zhannet Alimovna Sozaeva; Vera Vyacheslavovna Korennaya; Irina Vladimirovna Poddubnaya; Timur Tejmurazovich Valiev; Svetlana Nikolaevna Kondratenko; Mikhail Vitalyevich Ilyin

doi:10.1515/dmpt-2023-0027

Article

Predictive modeling of adverse drug reactions to tamoxifen therapy for breast cancer on base of pharmacogenomic testing

Ekaterina Olegovna Golubenko , Marina Ivanovna Savelyeva , Zhannet Alimovna Sozaeva , Vera Vyacheslavovna Korennaya , Irina Vladimirovna Poddubnaya , Timur Tejmurazovich Valiev , Svetlana Nikolaevna Kondratenko and Mikhail Vitalyevich Ilyin

Published/Copyright: July 20, 2023

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From the journal Drug Metabolism and Personalized Therapy Volume 38 Issue 4

Abstract

Objectives

The present study investigated the analysis of adverse drug reactions (ADRs) to tamoxifen (TAM) in breast cancer patients in relation to the carriage of genetic polymorphisms of genes encoding enzymes of CYP system and transporters of P-glycoprotein (Pg) and predictive models based on it.

Methods

A total of 120 women with breast cancer taking adjuvant TAM were examined for the gene polymorphisms such as CYP2D6*4, CYP3A5*3, CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3 and ABCB1 (C3435T). Allelic variants were determined using the real-time polymerase chain reaction method. The research material was double sampling of buccal epithelium. Medical history data and extracts from case histories were used as sources of medical information, on the basis of which questionnaires specially created by us were filled out.

Results

An associative analysis showed association with the development of ADRs to TAM indicating their clinical significance from different genetic polymorphisms of CYP2D6, CYP3A5, CYP2C9 and ABCB1. The complex associative analysis performed using mathematical modeling made it possible to build predictive risk models for the development of ADRs such as hot flashes, dyspepsia, bone pain, and asthenia.

Conclusions

Models that include both genetic and non-genetic determinants of ADRs of TAM may further improve the prediction of individual response to TAM.

Keywords: breast cancer; cytochromes P450; P-glycoprotein transporters; pharmacogenetics; polymorphism; tamoxifen

Corresponding author: Marina Ivanovna Savelyeva, MD, PhD, Professor, Department of Therapy, Institute of Continuous Professional Education, Yaroslavl State Medical University of the Ministry of Health of Russia, Yaroslavl, 150000, ul. Revolucionnaya, 5, Russia, E-mail: marinasavelyeva@mail.ru

Research ethics: Clinical studies of the research were conducted in accordance with all the relevant Russian national regulations, institutional policies, and in accordance with the principles of the Declaration of the World Medical Association (Edinburgh, 2000), and in accordance with the tenets of the Helsinki Declaration. The study was approved by the Research Ethics Committee of the Federal State Educational Institution of Additional Professional Education “Russian Medical Academy of Continuous Professional Education” of the Ministry of Health of Russia, Protocol No. 1 dated January 17, 2017, in accordance with the approved regulations for conducting clinical and experimental research at the Academy.
Informed consent: Written informed consent was obtained from all participants in the study before the beginning of any procedures especially pharmacogenetic testing.
Author contributions: Ekaterina O. Golubenko as a gynecologist has substantial contributions to the conception and design of data for the work; and statistical analysis of research results; and final approval of the version to be published; and integrity of any part of the work are appropriately investigated and resolved because she is a PhD degree candidate. Marina I. Savelyevа as a Professor of Clinical Pharmacology has substantial contributions to the interpretation of data for the work and drafting the work (writing an article in English); and revising it critically for important intellectual content; and final approval of the version to be published; and agreement to be accountable for all aspects of the work because she is a main scientific leader of this research study. Zhannet A. Sozaeva as a junior researcher of the Research Institute of Molecular and Personalized Medicine has substantial contributions to the pharmacogenetic testing, and interpretation of data for the work; and final approval of the version to be published; and agreement to be accountable for all aspects of the work. Vera V. Korennaya as a specialist in endoscopic gynecology has substantial contributions to the analysis of the research study in endoscopic results field; and revising the work critically for important intellectual content; and final approval of the version to be published; and agreement to be accountable for all aspects of the work. Irina V. Poddubnaya as Head of Oncology Department has substantial contributions to the conception and design of data for the work because she was a scientific supervisor of drug research in breast cancer; and revising the work critically for important intellectual content; and final approval of the version to be published; and agreement to be accountable for all aspects of the work. Timur T. Valiev as Head of Chemotherapy Hemoblastoses Department of Pediatric Oncology and Hematology has substantial contributions to the conception and design of data for the work; and revising it critically for important intellectual content especially in the pharmacogenetic data field; and final approval of the version to be published; and integrity of any part of the work are appropriately investigated and resolved. Svetlana N. Kondratenko as a Professor of Clinical Pharmacology has substantial contributions to the interpretation of data for the work, and drafting the article; and final approval of the version to be published; and agreement to be accountable for all aspects of the work. Mikhail V. Ilyin as Head of Therapy Department has substantial contributions to the revising of all statistic data and to the building of preventing models of data for the work; and final approval of the version to be published.
Competing interests: The authors state no conflict of interest.
Research funding: None declared.

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Received: 2023-03-26

Accepted: 2023-05-19

Published Online: 2023-07-20

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Articles in the same Issue

https://doi.org/10.1515/dmpt-2023-0027

Keywords for this article

breast cancer; cytochromes P450; P-glycoprotein transporters; pharmacogenetics; polymorphism; tamoxifen