phgenomicsФармакогенетика и фармакогеномикаPharmacogenetics and Pharmacogenomics2588-05272686-8849LLC "Izdatelstvo OKI"10.24411/2588-0527-2019-10039phgenomics-150Research ArticleФАРМАКОГЕНЕТИЧЕСКИЕ ИССЛЕДОВАНИЯPHARMACOGENETICS STUDYИсследование генетических полиморфизмов системы биотрансформации тамоксифена при раке молочной железы: предварительные результатыOpportunities of the pharmacogenetic approach to personalized tamoxifen breast cancer therapy: preliminary resultshttps://orcid.org/0000-0002-2373-2250СавельеваМ. И.SavelyevaM. I.

Савельева Марина Ивановна - д. м. н., профессор кафедры клинической фармакологии и терапии, профессор кафедры патологии человека. SPIN-код: 2434-6458

Москва

Savelyeva Marina - MD, PhD, Professor of the Clinical Pharmacology and Therapy Department. SPIN-code: 2434-6458

Moscow

marinasavelyeva@mail.ruhttps://orcid.org/0000-0001-6410-7120ДудинаИ. А.DudinaI. A.

Дудина Ирина Александровна - студентка 6 курса факультета «Медицина будущего». SPIN-код: 6732-4992

Москва

Dudina Irina - MD student. SPIN-code: 6732-4992

Moscow

https://orcid.org/0000-0001-6680-9847ЗахаренковаЮ. С.ZaharenkovaJ. S.

Захаренкова Юлия Сергеевна - студентка 6 курса факультета «Медицина будущего». SPIN-код: 7754-0526

Москва

Zakharenkova Julia - MD student. SPIN-code: 7754-0526

Moscow

https://orcid.org/0000-0002-2968-4499ИгнатоваА. К.IgnatovaA. K.

Игнатова Анна Константиновна - студентка 6 курса факультета «Медицина будущего». SPIN-код: 5837-6124

Москва

Ignatova Julia - MD student. SPIN-code: 5837-6124

Moscow

https://orcid.org/0000-0003-3505-8520РыжиковаК. А.RyzhikovaK. A.

Рыжикова Кристина Анатольевна - н. с. отдела молекулярной медицины.

Москва

Ryzhikova Kristina - Research Officer Department of Molecular medicine.

Moscow

СозаеваЖ. А.SozaevaZ. A.

Созаева Жаннет Алимовна - лаборант кафедры клинической фармакологии и терапии.

Москва

Sozaeva Zhannet - laboratory assistant of the Department of clinical pharmacology and therapy.

Moscow

https://orcid.org/0000-0002-0995-1801ПоддубнаяИ. В.PoddubnayaI. V.

Поддубная Ирина Владимировна - д. м. н., профессор, академик РАН, заведующая кафедрой онкологии, проректор по учебной работе и международному сотрудничеству. SPIN-код: 1146-9889

Москва

Poddubnaya Irina - MD, PhD, Academician of Russian Academy of Science, Professor, Head of Oncology Department. SPIN-code: 1146-9889

Moscow

ПерфильеваО. М.PerfilevaO. M.

Перфильева Оксана Михайловна - к. м. н., заместитель главного врача по медицинской части.

Москва

Oksana M. Perfileva - MD, PhD, Deputy of Chief Medical Officer for the Medical Unit.

Moscow

ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава РоссииРоссияFSBEI FPE Russian Medical Academy of Continuous Professional Education of Ministry of Healthcare of the Russian FederationRussian FederationФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава РоссииРоссияSechenov First Moscow State Medical UniversityRussian FederationНИЦ ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава РоссииРоссияResearch Centre of FSBEI FPE Russian Medical Academy of Continuous Professional Education of Ministry of Healthcare of the Russian FederationRussian FederationКлиника ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава РоссииРоссияClinic of FSBEI FPE Russian Medical Academy of Continuous Professional Education of Ministry of Healthcare of the Russian FederationRussian Federation201923032020012934Copyright © Савельева М.И., Дудина И.А., Захаренкова Ю.С., Игнатова А.К., Рыжикова К.А., Созаева Ж.А., Поддубная И.В., Перфильева О.М., 20192019Савельева М.И., Дудина И.А., Захаренкова Ю.С., Игнатова А.К., Рыжикова К.А., Созаева Ж.А., Поддубная И.В., Перфильева О.М.Savelyeva M.I., Dudina I.A., Zaharenkova J.S., Ignatova A.K., Ryzhikova K.A., Sozaeva Z.A., Poddubnaya I.V., Perfileva O.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmacogenetics-pharmacogenomics.ru/jour/article/view/150

Тамоксифен – селективный модулятор эстрогеновых рецепторов, препарат выбора при эндокринотерапии ER-позитивного рака молочной железы (РМЖ) у женщин в пременопаузе, а также в постклимактерическом периоде при наличии противопоказаний к приёму ингибиторов ароматазы. Тамоксифен является пролекарством и метаболизируется в более активные формы при участии ферментов цитохрома P450 (CYP): CYP2D6, CYP3A5, CYP2C9 и CYP2C19. Гены CYP являются полиморфными, поэтому среди пациенток наблюдаются различия в метаболизме тамоксифена, способствующие изменению концентрации метаболитов в сыворотке и, возможно, влияющие на клинический ответ и эффективность терапии РМЖ. В данной статье представлены предварительные результаты генетического тестирования женщин с раком молочной железы и анализ мировой литературы о клинической значимости различных генетических вариантов CYP2D6, CYP3A5, CYP2C9. Кроме того, в данной статье представлены демографические особенности в распространённости наиболее значимых полиморфизмов изучаемых генов. Важно, что с привлечением генетического исследования в рутинную клиническую практику появится возможность более эффективного назначения лекарственных препаратов с учётом фармакогенетического профиля пациентов, в том числе и тамоксифена.

Tamoxifen is the selective modulator of estrogen receptors. Nowadays, it is widely used for treatment of premenopausal women with ER(+) breast cancer likewise for postmenopausal women with treatment contraindications to aromatase inhibitors. Tamoxifen is a prodrug which is metabolized by cytochrome P450 (CYP): CYP2D6, CYP3A5, CYP2C9, CYP2C19 to active metabolites. There is high variability in the CYP genes therefore differences in Tamoxifen metabolism. This article presents preliminary results of genetic testing of 120 patients with breast cancer. Patients responded to the survey questionnaire, then samples of buccal epithelium were taken for genetic analysis of CYP2D6*4, CYP3A5*3, CYP2C9*2,3, CYP2C19*2,3, gene mutations by use of real time PCR. In addition, this article presents demographic features in the prevalence of the most significant polymorphisms of the studied genes. We suppose that routine genetic study before tamoxifen administration would help to predict individual intolerance and increase the efficacy of treatment.

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The authors declare that there are no conflicts of interest present.