Personalized approach to outpatient management of patients taking tamoxifen by gynecologists
- Authors: Golubenko E.O.1, Savelyeva M.I.2, Korennaya V.V.1, Podzolkova N.M.1
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Affiliations:
- Russian Medical Academy of Continuous Professional Education
- Yaroslavl State Medical University
- Issue: Vol 73, No 1 (2024)
- Pages: 29-39
- Section: Original study articles
- URL: https://journals.rcsi.science/jowd/article/view/254309
- DOI: https://doi.org/10.17816/JOWD608183
- ID: 254309
Cite item
Abstract
BACKGROUND: 30% of women with luminal breast cancer receiving adjuvant tamoxifen experience disease recurrence within 15 years. This demonstrates the wide variability in clinical response to tamoxifen. Both nongenetic (age, gender, body mass index, duration of drug use) and genetic factors have been described to influence the high variability of response to tamoxifen. Differences in the genes encoding the enzymes CYP2D6, CYP2C, and CYP3A (CYP2D6*4, CYP3A5*3, CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3) and the ABCB1 gene (C3435T) may also be the main factors of susceptibility to the occurrence of undesirable effects when taking tamoxifen, which in turn may lead to decreased patient adherence to therapy.
AIM: The aim of this study was to create a concept and an algorithm for a personalized approach to outpatient management of patients taking tamoxifen by a gynecologist in connection with the carriage of polymorphisms of cytochrome P450 and drug transporter genes.
MATERIALS AND METHODS: In 2017–2018, the outpatient records of 230 patients with breast cancer were analyzed retrospectively. A single-stage pharmacogenetic study of 120 women with stage I–III luminal breast cancer taking tamoxifen was conducted prospectively for the presence of cytochrome P450 gene polymorphisms using the polymerase chain reaction method and assessing associations with adverse drug reactions, and 54 patients were interviewed after five-year follow-up to assess adherence and satisfaction with medical supervision.
RESULTS: The likelihood of developing endometrial hyperplasia has been shown to increase while taking tamoxifen with increasing average age, body mass index, duration of tamoxifen use, and postmenopause. Significant associations have been identified between the carriage of the CYP2D6, CYP2C9, CYP2C19, CYP3A5, and ABCB1 gene polymorphisms and the development of adverse drug reactions. Predictive models have been developed to determine the risk of adverse drug reactions. All studied adverse drug reactions associated with various genetic polymorphisms predominated in the group of patients who stopped taking tamoxifen due to poor intolerance. Gynecologists regularly observed 57.4% of patients. Moreover, the higher the adherence to therapy was, the higher was the regularity of observation by a gynecologist.
CONCLUSIONS: A plan for outpatient management of patients receiving adjuvant endocrine therapy with tamoxifen by a gynecologist has been developed.
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##article.viewOnOriginalSite##About the authors
Ekaterina O. Golubenko
Russian Medical Academy of Continuous Professional Education
Author for correspondence.
Email: kate.golubenko@yandex.ru
ORCID iD: 0000-0002-6968-862X
MD
Russian Federation, MoscowMarina I. Savelyeva
Yaroslavl State Medical University
Email: marinasavelyeva@mail.ru
ORCID iD: 0000-0002-2373-2250
MD, Dr. Sci. (Med), Assistant Professor
Russian Federation, YaroslavlVera V. Korennaya
Russian Medical Academy of Continuous Professional Education
Email: drkorennaya@mail.ru
ORCID iD: 0000-0003-1104-4415
MD, Cand. Sci. (Med.), Assistant Professor
Russian Federation, MoscowNatalia M. Podzolkova
Russian Medical Academy of Continuous Professional Education
Email: podzolkova@gmail.com
ORCID iD: 0000-0002-8204-8336
MD, Dr. Sci. (Med.), Professor
Russian Federation, MoscowReferences
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