medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2024-246medsovet-8397Research ArticleТАРГЕТНАЯ ТЕРАПИЯTARGET THERAPY OF TUMORSРасширяя возможности терапии HER2-low метастатического рака молочной железы: опыт применения трастузумаба дерукстекана при агрессивном течении люминального HER2-low рака молочной железыExpanding the treatment options for HER2-low metastatic breast cancer: Experience with trastuzumab deruxtecan in aggressive luminal HER2-low breast cancerhttps://orcid.org/0000-0001-5289-7866ЛубенниковаЕ. В.LubennikovaE. V.

Лубенникова Елена Владимировна - к.м.н., старший научный сотрудник отделения противоопухолевой лекарственной терапии №1 с дневным стационаром отдела лекарственного лечения Научно-исследовательского института клинической онкологии им. Н.Н. Трапезникова.

115478, Москва, Каширское шоссе, д. 23

Elena V. Lubennikova - Cand. Sci. (Med.), Senior Researcher at the Department of Antitumor Drug Therapy No. 1 with a Day Hospital of the Department of Drug Treatment of the Scientific Research Institute of Clinical Oncology named after N.N. Trapeznikov.

23, Kashirskoye Shosse, Moscow, 115478

lubennikova@yandex.ruhttps://orcid.org/0000-0002-0105-9376ГаньшинаИ. П.GanshinaI. P.

Ганьшина Инна Петровна - к.м.н., ведущий научный сотрудник отделения противоопухолевой лекарственной терапии №1 с дневным стационаром отдела лекарственного лечения Научно-исследовательского института клинической онкологии им. Н.Н. Трапезникова.

115478, Москва, Каширское шоссе, д. 23

Inna P. Ganshina - Cand. Sci. (Med.), Leading Researcher at the Department of Antitumor Drug Therapy No. 1 with a Day Hospital of the Department of Drug Treatment of the Scientific Research Institute of Clinical Oncology named after N.N. Trapeznikov.

23, Kashirskoye Shosse, Moscow, 115478

ganshinainna77@mail.ruhttps://orcid.org/0000-0002-5084-4872МанукянМ. Ш.ManukyanM. Sh.

Манукян Марьям Шираковна - врач-онколог онкологического отделения противоопухолевой лекарственной терапии №2 с дневным стационаром отдела лекарственного лечения Научно-исследовательского института клинической онкологии им. Н.Н. Трапезникова.

115478, Москва, Каширское шоссе, д. 23

Mariam Sh. Manukyan - Oncologist of the Oncology Department of Antitumor Drug Therapy No. 2 with a Day Hospital of the Department of Drug Treatment of the Scientific Research Institute of Clinical Oncology named after N.N. Trapeznikov.

23, Kashirskoye Shosse, Moscow, 115478

manukyanmariam6@gmail.comhttps://orcid.org/0000-0003-3931-1431ТюринИ. Е.TyurinI. E.

Тюрин Игорь Евгеньевич - д.м.н., профессор, заместитель директора по науке Научно-исследовательского института клинической и экспериментальной онкологии.

115478, Москва, Каширское шоссе, д. 23

Igor E. Tyurin - Dr. Sci. (Med.), Professor, Deputy Director for Science, Research Institute of Clinical and Experimental Oncology.

23, Kashirskoye Shosse, Moscow, 115478

igortyurin@gmail.comhttps://orcid.org/0000-0001-7728-9533АртамоноваЕ. В.ArtamonovaE. V.

Артамонова Елена Владимировна - д.м.н., профессор кафедры онкологии и лучевой терапии, Российский НИМУ имени Н.И. Пирогова; заведующая кафедрой онкологии и торакальной хирургии, Московский ОНИКИ т имени М.Ф. Владимирского; заведующая отделением противоопухолевой лекарственной терапии №1 с дневным стационаром отдела лекарственного лечения Научно-исследовательского института клинической онкологии им. Н.Н. Трапезникова, НМИЦО имени Н.Н. Блохина.

115478, Москва, Каширское шоссе, д. 23; 117997, Москва, ул. Островитянова, д. 1; 129110, Москва, ул. Щепкина, д. 61/2, корп. 1

Elena V. Artamonova - Dr. Sci. (Med.), Professor of the Department of Oncology and Radiation Therapy, Pirogov RNRMU; Head of the Department of Oncology and Thoracic Surgery, MRRCI named after M.F. Vladimirsky Head of the Department of Antitumor Drug Therapy No. 1 with a day hospital of the Department of Drug Treatment of the Scientific Research Institute of Clinical Oncology named after. N.N. Trapeznikov, Blokhin NMRCO.

1, Ostrovityanov St., Moscow, 117997; 61/2, Bldg. 1, Schepkin St., Moscow, 129110; 23, Kashirskoye Shosse, Moscow, 115478

artamonovae@mail.ruНациональный медицинский исследовательский центр онкологии имени Н.Н. БлохинаРоссияBlokhin National Medical Research Center of OncologyRussian FederationНациональный медицинский исследовательский центр онкологии имени Н.Н. Блохина; 2 Российский национальный исследовательский медицинский университет имени Н.И. Пирогова; Московский областной научно-исследовательский клинический институт имени М.Ф. ВладимирскогоРоссияBlokhin National Medical Research Center of Oncology; Pirogov Russian National Research Medical University; Moscow Regional Research Clinical Institute named after M.F. VladimirskyRussian Federation2024240720240106673Copyright © Лубенникова Е.В., Ганьшина И.П., Манукян М.Ш., Тюрин И.Е., Артамонова Е.В., 20242024Лубенникова Е.В., Ганьшина И.П., Манукян М.Ш., Тюрин И.Е., Артамонова Е.В.Lubennikova E.V., Ganshina I.P., Manukyan M.S., Tyurin I.E., Artamonova E.V.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/8397

Полярное деление рака молочной железы на HER2-позитивный и HER2-негативный подтипы длительное время оставалось клинически обоснованным. Однако до 60% HER2-негативных опухолей имеют экспрессию рецептора HER2, определяемую при иммуногистохимическом исследовании на 1+ или 2+. В отсутствие амплификации гена такие опухоли относят к HER2-low. Попытки применения классических анти-HER2-агентов не улучшали результатов лечения для этих опухолей. Разработка конъюгата «антитело – цитостатик» нового поколения трастузумаба дерукстекана, нацеленного на рецептор HER2, меняет диагностические подходы и клиническую практику лечения метастатического HER2-low рака молочной железы. Настоящей революцией стали результаты исследования III фазы DESTINY-Breast04 по изучению трастузумаба дерукстекана у больных метастатическим раком молочной железы с низкой экспрессией HER2. Медиана выживаемости без прогрессирования в когорте пациентов, получавших трастузумаб дерукстекан, составила 9,9 мес. против 5,1 мес. в группе пациентов, получавших стандартную химиотерапию по выбору врача (ОР 0,50; 95% ДИ 0,40–0,63, P < 0,001), медиана общей выживаемости – 23,4 мес. против 16,8 мес. соответственно (ОР 0,64; 95% ДИ 0,48–0,86, P = 0,003). Объективный ответ на фоне терапии трастузумабом дерукстеканом зафиксирован в 52,3% случаев против 16,3% в группе стандартного лечения. Терапия новым препаратом продемонстрировала благоприятный профиль безопасности и не снижала качество жизни пациентов. В данной публикации мы представляем собственный опыт лечения трастузумабом дерукстеканом пациентки с метастатическим люминальным HER2-low раком молочной железы. Несмотря на агрессивное течение, количество предшествующих линий терапии и массивное поражение печени, применение трастузумаба дерукстекана позволило в течение 2 лет контролировать болезнь при сохранении высокого качества жизни пациентки. Трастузумаб дерукстекан – это новая эффективная опция для лечения HER2-low метастатического рака молочной железы.

The polar division of breast cancer into HER2-positive and HER2-negative subtypes has long remained clinically significance. However, up to 60% of HER2-negative tumors have HER2 receptor expression assessed by immunohistochemistry as 1+ or 2+. In the absence of gene amplification, such tumors are classified as HER2-low. Сlassical anti-HER2 agents have not improved treatment outcomes for these tumors. The development of a new generation antibody-cytostatic conjugate, trastuzumab deruxtecan, targeting the HER2 receptor, is changing diagnostic approaches and clinical practice in the treatment of metastatic HER2-low breast cancer. The results of the phase III DESTINY-Breast04 study of trastuzumab deruxtecan in patients with metastatic breast cancer with low HER2 expression became a real revolution. The median progression-free survival in the cohort of patients receiving trastuzumab deruxtecan was 9.9 months versus 5.1 months in the group of patients receiving standard chemotherapy at the physician’s choice (RR 0.50; 95% CI 0.40–0.63, P = 0.003). An objective response during therapy with trastuzumab deruxtecan was recorded in 52.3% of cases versus 16.3% in the standard treatment group. Therapy with the new drug demonstrated a favorable safety profile and did not reduce the quality of life. In this publication, we present our own experience of treating a patient with metastatic luminal HER2-low breast cancer with trastuzumab deruxtecan. Despite the aggressive course, the number of previous lines of therapy and massive liver damage, the use of trastuzumab deruxtecan made it possible to control the disease for 2 years while maintaining a high quality of life for the patient. Trastuzumab deruxtecan is a new effective treatment option for HER2-low metastatic breast cancer.

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