medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2020-9-57-61medsovet-5701Research ArticleТАРГЕТНАЯ ТЕРАПИЯ ОПУХОЛЕЙTarget therapy of tumorsPARP-ингибиторы в лечении больных метастатическим раком молочной железы с герминальными мутациями в генах BRCA1/2. Опыт применения талазопариба в клинической практикеPARP inhibitors in the treatment of metastatic breast cancer patients with germline BRCA1/2 mutations. Experience of treatment with talazoparib in clinical practiceФроловаМ. А.FrolovaM. A.

Фролова Мона Александровна, к.м.н., научный сотрудник онкологического отделения лекарственных методов лечения (химиотерапевтического) №2

115478, Москва, Каширское шоссе, д. 24

Mona A. Frolova, Cand. Of Sci. (Med.), Research Assistant Cancer Drug Therapy Department (Chemotherapeutic No. 2)

24, Kashirskoye Shosse, Moscow, 115478

drfrolova@yandex.ruГлазковаЕ. В.GlazkovaE. V.

Глазкова Елена Владимировна, аспирант онкологического отделения лекарственных методов лечения (химиотерапевтического) №2

115478, Москва, Каширское шоссе, д. 24

Elena V. Glazkova, Aspirant, Cancer Drug Therapy Department (Chemotherapeutic No. 2)

24, Kashirskoye Shosse, Moscow, 115478

mdglazkiova@gmail.comСтенинаМ. Б.SteninaM. B.

Стенина Марина Борисовна, д.м.н., ведущий научный сотрудник онкологического отделения лекарственных методов лечения (химиотерапевтического) №2

115478, Москва, Каширское шоссе, д. 24

Marina B. Stenina, Doct. of Sci. (Med.), Senior Research Assistant, Cancer Drug Therapy Department (Chemotherapeutic No. 2)

24, Kashirskoye Shosse, Moscow, 115478

mstenina@mail.ruНациональный медицинский исследовательский центр онкологии им. Н.Н. БлохинаРоссияN.N. Blokhin National Medical Research Center of OncologyRussian Federation202027072020095761Copyright © Фролова М.А., Глазкова Е.В., Стенина М.Б., 20202020Фролова М.А., Глазкова Е.В., Стенина М.Б.Frolova M.A., Glazkova E.V., Stenina M.B.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/5701

Около 10% всех случаев рака молочной железы (РМЖ) возникает у носителей мутаций в генах BRCA1/2. Ведущей функцией белковых продуктов генов BRCA1/2 является восстановление двунитевых разрывов ДНК посредством процесса гомологичной репарации. Поли-(АДФ рибоза)-полимеразы (PARP) также вовлечены в процесс репарации ДНК. Их функцией является восстановление однонитевых разрывов ДНК путем эксцизионной репарации оснований. PARPингибиторы представляют собой современную опцию лечения метастатического BRCA-ассоциированного HER2- негативного РМЖ. Их действие основано на принципе «синтетической летальности» в условиях дисфункции BRCA, когда нарушаются оба процесса репарации ДНК, – гомологичная рекомбинация и эксцизионная репарация оснований. Это приводит к апоптозу опухолевых клеток. В настоящее время в России для лечения метастатического BRCAассоциированного HER2-негативного РМЖ зарегистрированы 2 PARP-ингибитора – олапариб и талазопариб. Эффективность олапариба и талазопариба, по сравнению со стандартной химиотерапией, изучалась в схожих по дизайну исследованиях III фазы OlympiAD и EMBRACA. Выигрыш в выживаемости, приемлемый профиль токсичности, а также положительное влияние на качество жизни позволяют рекомендовать использование PARP-ингибиторов в схемах лечения метастатического BRCA­ассоциированного РМЖ. Очень важна роль PARP-ингибиторов в лечении метастатического тройного негативного РМЖ, учитывая агрессивное течение данного подтипа и ограниченное количество эффективных опций терапии. Мы представляем клинический случай применения талазопариба в качестве 4-й линии терапии у больной метастатическим тройным негативным РМЖ.

Germline BRCA1/2 mutations account for about 10% of all breast cancer. BRCA1/2 proteins are involved in homologous recombination - DNA double-strand break repair mechanism. Poly-(ADP ribose) polymerases (PARP) are required to repair DNA single-strand breaks through base excision repair. PARP inhibitors represent a modern option of treatment of metastatic HER2 negative breast cancer with germline BRCA1/2 mutations. Mechanism of action of PARP inhibitors is based on the concept of synthetic lethality under conditions of BRCA dysfunction, when both DNA repair mechanisms, homologous recombination and base excision repair, are impaired. This leads to the apoptosis of cancer cells. Currently two PARP inhibitors are registered in Russia for the treatment of BRCA-associated metastatic HER2 negative breast cancer – olaparib and talazoparib. Efficacy of PARP inhibitors olaparib and talazoparib versus standard chemotherapy has been studied in very similarly designed phase III trials OlympiAD и EMBRACA. Benefit in the progression free survival, acceptable toxicity profile and positive impact on quality of life support inclusion of PARP inhibitors in treatment schemes of metastatic BRCAassociated breast cancer. Very important is the role of PARP inhibitors in treatment of very aggressive triple negative breast cancer with limited number of effective therapy options. We represent here a clinical case of treatment of metastatic triple negative breast cancer with talazoparib in 4th line of therapy.

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