Possibilities of a pharmacogenetic approach to solving gynecological problems in patients taking tamoxifen: a literature review

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Abstract

Endocrine therapy for 5–10 years is the standard treatment for women with ER-positive breast cancer (BC). However, the side effects of endocrine therapy with tamoxifen (TAM) reduce the quality of life of BC patients and adversely affect treatment compliance. Currently, the problem of hyperplastic processes and endometrial cancer against the background of long-term use of TAM is especially relevant, because the incidence of endometrial pathology is associated with the duration of TAM use. pharmacogenetics is an important factor predisposing to the occurrence of adverse drug reactions (ADR), incl. endometrial hyperplasia, when taking TAM. Differences in the genes encoding the enzymes CYP2D6, CYP2C9 and CYP2C19, namely, CYP2D6*4, CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3, as well as the polymorphic marker of the ABCB1 gene (C3435T), encoding the glycoprotein transport protein – P, may be the main predisposition factor to the occurrence of side effects when taking TAM, which in turn leads to a decrease in patient adherence to therapy. However, at the moment, algorithms for monitoring such patients have not been developed, and risk factors that increase the likelihood of ADRs when taking TAM have not been fully identified. An integrated approach to assessing ADRs to TAM, taking into account pharmacogenetic testing data, and resulting predictive models that include both genetic and non-genetic determinants of response may further improve the prediction of individual response to TAM.

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About the authors

E. O. Golubenko

Russian Medical Academy of Continuous Professional Education

Author for correspondence.
Email: kate.golubenko@yandex.ru
ORCID iD: 0000-0002-6968-862X

Obstetrician-Gynecologist, Postgraduate Degree Seeker, Department of Obstetrics and Gynecology

Russian Federation, Moscow

M. I. Savelyeva

Yaroslavl State Medical University

Email: kate.golubenko@yandex.ru
ORCID iD: 0000-0002-2373-2250
Russian Federation, Yaroslavl

I. V. Poddubnaya

Russian Medical Academy of Continuous Professional Education

Email: kate.golubenko@yandex.ru
ORCID iD: 0000-0002-0995-1801
Russian Federation, Moscow

V. V. Korennaya

Russian Medical Academy of Continuous Professional Education

Email: kate.golubenko@yandex.ru
ORCID iD: 0000-0003-1104-4415
Russian Federation, Moscow

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2. Figure. Scheme of phase I metabolism of TAM [21]

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