Clinical significance of genetic polymorphism of tamoxifen metabolic enzymes and transporters in breast cancer: results of a population-based cohort study


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Abstract

Endocrine therapy for 5-10 years is the standard treatment for women with ER-positive breast cancer (BC). Despite ongoing endocrine therapy, approximately 30% of patients with breast cancer will have a relapse of the disease within 15 years after treatment, indicating a wide variability in the clinical response to tamoxifen treatment. The pharmacological response of tamoxifen may be affected by varying degrees of activity of cytochrome P-450 (CYP) enzymes and P-glycoprotein (Pg) transporters, due to the mass of polymorphisms in the genes of these enzymes. The article presents the results of a prospective pharmacogenetic cohort study analyzing the clinical manifestations of complications of endocrine therapy with tamoxifen in adjuvant mode with assessment of the relationship between the carriage of genetic polymorphisms of genes encoding enzymes of the cytochrome P-450 system and proteins - drug transporters, with the development of adverse events in BC patients. The study involved 120 women with breast cancer who underwent genetic testing for polymorphisms of the CYP and Pg enzyme genes. As a result of associative analysis, their relationship with the development of adverse drug reactions to tamoxifen was shown, indicating the clinical significance of various CYP2D6, CYP3A5, CYP2C9 and ABCB1genetic polymorphisms. Thus, models that include both genetic and non-genetic determinants of response may further improve the prediction of individual response to tamoxifen. It is necessary to develop specific clinical guidelines for conducting complex pharmacogenomic testing, which would help to expand our knowledge for the development of more effective and optimal methods of anti-relapse treatment of breast cancer survivors.

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About the authors

Ekaterina O. Golubenko

Center for Immunology and Reproduction

Email: kate.golubenko@yandex.ru
Obstetrician-Gynecologist Moscow, Russia

M. I Savelyeva

Yaroslavl State Medical University

aroslavl, Russia

Zh. A Sozaeva

ussian Medical Academy of Continuous Professional Education

Moscow, Russia

I. V Poddubnaya

ussian Medical Academy of Continuous Professional Education

Moscow, Russia

V. V Korennaya

ussian Medical Academy of Continuous Professional Education

Moscow, Russia

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