Perspectives of pharmacogenetics approach to personalized tamoxifen therapy

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Abstract


Tamoxifen is the selective modulator of estrogen receptors. Nowadays, it is widely used in the treatment of ER(+) breast cancer and substantially decreases the risks of recurrence and disease progression. However, high interindividual variability in response is observed, calling for a personalized approach to tamoxifen treatment. Tamoxifen is metabolized by cytochrome P450, resulting in the formation of active metabolites, including 4-hydroxy-tamoxifen and endoxifen. The effectiveness and success of treatment depends largely on concentrations of the active tamoxifen metabolites in blood plasma. Polymorphisms in the genes encoding these enzymes are proposed to influence on pharmacokinetics and pharmacodynamics of tamoxifen. Therefore, pharmacogenetic approach may form the basis of personalized treatment of breast cancer. In this systematic review, we analyze all current data about the potential use of genotyping of CYP2D6, CYP3A4/5, CYP2B6 to predict an individual response on tamoxifen treatment.


Marina I. Savelyeva

Russian Medical Academy of Continuous Professional Education; I.M. Sechenov First Moscow State Medical University

Author for correspondence.
Email: marinasavelyeva@mail.ru
ORCID iD: 0000-0002-2373-2250
SPIN-code: 2434-6458

Russian Federation, 2/1, Barrikadnaya st., Moscow, 125993; 8-2, Trubetskaya street, Moscow, 119992

MD, PhD, Professor

Julia S. Panchenko

 I.M. Sechenov First Moscow State Medical University

Email: juli_panch@mail.ru
ORCID iD: 0000-0001-6680-9847
SPIN-code: 7754-0526

Russian Federation, 8-2, Trubetskaya street, Moscow, 119992

MD student

Irina A. Urvantseva

 I.M. Sechenov First Moscow State Medical University

Email: miss.rowe@yandex.ru
ORCID iD: 0000-0001-6410-7120
SPIN-code: 6732-4992

Russian Federation, 8-2, Trubetskaya street, Moscow, 119992

MD student

Anna K. Ignatova

I.M. Sechenov First Moscow State Medical University 

Email: ign_a95@mail.ru
ORCID iD: 0000-0002-2968-4499
SPIN-code: 5837-6124

Russian Federation, 8-2, Trubetskaya street, Moscow, 119992

MD student

Irina V. Poddubnaya

Russian Medical Academy of Continuous Professional Education

Email: ivprectorat@inbox.ru
ORCID iD: 0000-0002-0995-1801
SPIN-code: 1146-9889

Russian Federation, 2/1, Barrikadnaya st., Moscow, 125993

MD, Professor

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