medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2021-20-54-61medsovet-6580Research ArticleТАРГЕТНАЯ ТЕРАПИЯ ОПУХОЛЕЙTarget therapy of tumorsИзучение молекулярных характеристик метастатических очагов как основа индивидуализации лечения при диссеминированном раке молочной железы. Есть ли место CDK4/6-ингибиторам в поздних линиях терапии после химиотерапевтических режимов?Molecular features evaluation of metastatic foci as the basis for metastatic breast cancer treatment personalization. Is there a place of CDK4/6-inhibitors in late-line therapy after chemotherapeutic regimens?https://orcid.org/0000-0002-0698-7710СтуканьА. И.StukanA. I.

к.м.н., врач-онколог координационного отдела лекарственного обеспечения, 350040, Краснодар, ул. Димитрова, д. 146;

ассистент кафедры онкологии с курсом торакальной хирургии, 350063, Краснодар, ул. Митрофана Седина, д. 4

Cand. Sci (Med.), Medical Oncologist, Drug Supply Coordination Department, 146, Dimitrov St., Krasnodar, 350040;

Assistant of the Department of Oncology with the Сourse of Thoracic Surgery, 4, Mitrofan Sedin St., Krasnodar, 350063

jolie86@bk.ruhttps://orcid.org/0000-0001-7127-7945ГоряиноваА. Ю.GoryainovaA. Y.

заведующая координационным отделом лекарственного обеспечения, 350040, Краснодар, ул. Димитрова, д. 146;

ассистент кафедры онкологии с курсом торакальной хирургии, 350063, Краснодар, ул. Митрофана Седина, д. 4

Medical Oncologist, Head of the Drug Supply Coordination Department, 146, Dimitrov St., Krasnodar, 350040;

Assistant of the Department of Oncology with the Course of Thoracic Surgery, 4, Mitrofan Sedin St., Krasnodar, 350063

mashelueva@yandex.ruhttps://orcid.org/0000-0002-6866-1425ЛымарьЕ. В.LymarE. V.

врач-онколог координационного отдела лекарственного обеспечения, 

350040, Краснодар, ул. Димитрова, д. 146

Medical Oncologist, Drug Supply Coordination Department, 

146, Dimitrov St., Krasnodar, 350040

tsari29@mail.ruhttps://orcid.org/0000-0002-8715-2992ШаровС. В.SharovS. V.

к.м.н., заместитель главного врача по лекарственному обеспечению, 350040, Краснодар, ул. Димитрова, д. 146;

ассистент кафедры онкологии с курсом торакальной хирургии, 350063, Краснодар, ул. Митрофана Седина, д. 4

Cand. Sci (Med.), Deputy Head for Drug Supply, 146, Dimitrov St., Krasnodar, 350040;

Assistant of the Department of Oncology with the Сourse of Thoracic Surgery, 4, Mitrofan Sedin St., Krasnodar, 350063

https://orcid.org/0000-0002-0006-3306АнтиповаВ. В.AntipovaV. V.

врач-стажер 9-го онкологического отделения, 350040, Краснодар, ул. Димитрова, д. 146;

аспирант кафедры онкологии с курсом торакальной хирургии, 350063, Краснодар, ул. Митрофана Седина, д. 4

Medical Intern at the 9th Oncology Department, 146, Dimitrov St., Krasnodar, 350040;

Graduate Student of the Department of Oncology with the Course of Thoracic Surgery, 4, Mitrofan Sedin St., Krasnodar, 350063

viktoryant@mail.ruКлинический онкологический диспансер №1; Кубанский государственный медицинский университетРоссияClinical Oncologic Dispensary No. 1; Kuban State Medical UniversityRussian FederationКлинический онкологический диспансер №1РоссияClinical Oncologic Dispensary No. 1Russian FederationКлинический онкологический диспансер №1; Кубанский государственный медицинский университетРоссияClinical Oncologic Dispensary No. 1; Kuban State Medical UniversityRussian Federation2021091220210205461Copyright © Стукань А.И., Горяинова А.Ю., Лымарь Е.В., Шаров С.В., Антипова В.В., 20212021Стукань А.И., Горяинова А.Ю., Лымарь Е.В., Шаров С.В., Антипова В.В.Stukan A.I., Goryainova A.Y., Lymar E.V., Sharov S.V., Antipova V.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/6580

Проблема терапии метастатического рака молочной железы неразрывно связана с клональной селекцией как в процессе эволюции опухоли, так и под воздействием предшествующего лечения. При этом существенное значение для индивидуализации лечения приобретает изучение характера микроокружения метастатической ниши и молекулярно-генетические особенности метастазов. Установлено, что клетки первичной опухоли и циркулирующие опухолевые клетки оказывают непосредственное влияние на подготовку преметастатической ниши. При этом характер взаимодействия зависит от органа метастатического поражения. В  нескольких исследованиях показаны различия экспрессии эстрогеновых рецепторов, прогестероновых рецепторов и рецептора эпидермального фактора роста (HER2neu) между первичной опухолью и метастатическим очагом. В исследованиях выявлены преимущества комбинированной гормонотерапии (КГТ) совместно с ингибиторами CDK4/6 в сравнении с гормонотерапией (ГТ) с увеличением показателей выживаемости в 1-й и 2-й линиях ГТ, а также после 1-й линии химиотерапии (ХТ). Однако имеются лишь некоторые данные о пациентах с предлеченностью несколькими линиями химиотерапии, несмотря на доказанную эффективность монотерапии абемациклибом в поздних линиях лечения после химиотерапии. В представленном ретроспективном исследовании более чем у половины больных до ингибиторов CDK4/6 была назначена паллиативная ХТ при прогрессировании. Основные метастатические очаги при биопсии представляли люминальные типы, однако была отмечена утрата экспрессии рецептора прогестерона при изначальном люминальном А-подтипе. На момент среза данных у большинства пациентов отмечается длительный клинический эффект, улучшение самочувствия и уменьшение болевого синдрома, в т.ч. в поздних линиях терапии после химиотерапевтических режимов. На основании представленного ретроспективного исследования возможно рассматривать назначение CDK4/6-ингибиторов как дополнительную опцию для поздних линий терапии диссеминированного процесса при доказанном гормонрецептор-положительном HER2neu-негативном рецепторном статусе метастатического очага. 

The problem of metastatic breast cancer treatment is linked with clonal selection both in the process of tumor evolution and under the  influence of  previous treatment. The  analysis of  metastatic niche microenvironment and the  molecular genetic features become essential for treatment individualization. Studies demonstrate hormonal expression and epidermal growth factor receptor (HER2neu) discordance between the primary tumor and the metastatic focus. The advantages of combined hormone therapy (CНT) with CDK4/6 inhibitors were revealed in comparison with hormone therapy (НT) with survival rates benefits in the 1st and 2nd lines of НT, as well as after the 1st line of chemotherapy in clinical trials. However, there are lack of data on patients with multiple lines of chemotherapy. In the present retrospective study, more than half of the patients were treated palliative chemotherapy before administration of CDK4/6 inhibitors. Main metastatic foci represented luminal types after biopsy, however, loss of progesterone receptor expression was noted with the initial luminal A-subtype. At the time of the data cut-off, most patients have a longterm clinical effect, improvement conditions and reduction of pain, including the cases of late line CHT setting after chemotherapeutic regimens. Taking into account the heterogeneity of metastatic breast cancer, clonal selection and phenotype discordance there is the crucial need for molecular and genetic characteristics of the metastatic process. At the same time it is possible to consider the  appointment of  combined hormone therapy with CDK4/6  inhibitors as additional option for  late-line treatment of the disseminated process. Prospective studies on combined hormonal therapy with CDK4/6 inhibitors in metastatic breast cancer in late lines of therapy with proven HR+HER2neu-negative receptor status of the metastatic focus are strongly recommended. 

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