Tumors of female reproductive systemTumors of female reproductive systemОпухоли женской репродуктивной системы1994-40981999-8627Publishing House ABV Press137410.17650/1994-4098-2025-21-2-47-59MAMMOLOGY. REVIEWSМАММОЛОГИЯ. ОБЗОРНЫЕ СТАТЬИThe role of ribociclib in the treatment of early hormone receptor-positive HER2-negative breast cancer: 4-year results of the randomized controlled phase 3 trial NATALEE and their reconsideration for clinical practiceМесто рибоциклиба в лечении раннего гормонозависимого HER2-отрицательного рака молочной железы: 4-летние результаты рандомизированного контролируемого исследования III фазы NATALEE и их переосмысление для клинической практикиhttps://orcid.org/0000-0002-1124-6802KolyadinaI. V.КолядинаИ. В.
Russian Federation

2 / 1 Barrikadnaya St., Moscow 125993

4 Akademika Oparina St., Moscow 117198

125993 Москва, ул. Баррикадная, 2 / 1, стр. 1

117997 Москва, ул. Академика Опарина, 4

Russian Medical Academy of Postgraduate Education, Ministry of Health of RussiaФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава РоссииV. I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии им. акад. В. И. Кулакова» Минздрава России0308202521247590108202501082025https://ojrs.abvpress.ru/ojrs/article/view/1374

This review presents the relevance of escalating pathogenetic treatment in patients with hormone receptor-positive breast cancer, identifies key goals for prescribing adjuvant combined endocrine therapy with CDK4 / 6 inhibitors in patients with stage II–III breast cancer, and presents 3- and 4-year results of the randomized controlled trial NATALEE. Studies comparing oncological outcomes of “traditional” drug regimens and combined endocrine therapy with ribociclib in patients with similar characteristics are demonstrated. Data on estimating the size of a population of patients with characteristics equivalent to those in the NATALEE trial for prescribing ribociclib in routine practice are presented.

В настоящем обзоре отражена актуальность эскалации патогенетического лечения у больных с гормонозависимым раком молочной железы, обозначены ключевые цели назначения адъювантной комбинированной эндокринотерапии с ингибиторами CDK4 / 6 у пациентов с раком молочной железы II–III стадий, представлены 3- и 4-летние результаты рандомизированного контролируемого исследования NATALEE. Продемонстрированы исследования по сравнению онкологических исходов «традиционных» лекарственных режимов и комбинированной эндокринотерапии с рибоциклибом у пациентов с аналогичными характеристиками. Представлены данные оценки размера популяции больных с характеристиками, эквивалентными таковым в исследовании NATALEE, для назначения рибоциклиба в рутинной практике.

hormone receptor-positive breast canceradjuvant endocrine therapyCDK4 / 6 inhibitorribociclibmetastatic cascadetumor cell dormancyrisk of recurrencetreatment escalationinvasive disease-free survivaldistant desease-free survivalгормонозависимый рак молочной железыадъювантная эндокринотерапияингибитор CDK4 / 6рибоциклибметастатический каскадпериод покоя опухолевых клетокриск рецидиваэскалация лечениявыживаемость без инвазивного заболеваниявыживаемость без отдаленных метастазовTyulyandin S.A., Artamonova E.V., Zhigulev A.N. et al. Breast cancer. RUSSCO practical recommendations, part 1.2. Zlokachestvennye opukholi = Malignant Tumors 2024;14(3s2): 32–81. (In Russ.). DOI: 10.18027/2224-5057-2024-14-3s2-1.2-01Тюляндин С.А., Артамонова Е.В., Жигулев А.Н. и др. Рак молочной железы. Практические рекомендации RUSSCO, часть 1.2. Злокачественные опухоли 2024;14(3s2):32–81. DOI: 10.18027/2224-5057-2024-14-3s2-1.2-01Takahashi N., Shimizu C., Shimomura A., Toi M. Role of abemaciclib in primary breast cancer: A narrative review of MonarchE. Transl Breast Cancer Res 2022;3:3. DOI: 10.21037/tbcr-21-27Slamon D., Fasching P.A., Hurvitz S. et al. Rationale and trial design of NATALEE: A phase III trial of adjuvant ribociclib + endocrine therapy versus endocrine therapy alone in patients with HR+/HER2– early breast cancer. Ther Adv Med Oncol 2023;15:17588359231178125. DOI: 10.1177/17588359231178125Johnston S., Toi M., O’Shaughnessy J. et al. Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): Results from a preplanned interim analysis of a randomised, open-label, phase 3 trial. Lancet Oncol 2023;24(1):77–90. DOI: 10.1016/S1470-2045(22)00694-5Harbeck N., Rastogi P., O’Shaughnessy J. et al. Adjuvant abemaciclib plus endocrine therapy for HR+, HER2–, high-risk early breast cancer: Results from a preplanned monarchE overall survival interim analysis, including 5-year efficacy outcomes. Ann Oncol 2023;34(Suppl 2):S1254–335. DOI: 10.1016/S0923-7534(23)04149-2Pan H., Gray R., Braybrooke J. et al. 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years. N Engl J Med 2017;377:1836–46. DOI: 10.1056/NEJMoa1701830Beckwitt C. Breast cancer metastatic dormancy and emergence, a role for adjuvant statin therapy. University of Pittsburgh, 2018.Tremont A. Endocrine therapy for early breast cancer: Updated review. Ochsner J 2017;17(4):405–11.Zhang N., Pan L., Weng T. et al. Chemotherapy combined with endocrine therapy: Old wine in a new bottle? Clin Breast Cancer 2024;24(8):e737–47. DOI: 10.1016/j.clbc.2024.08.018Herbig U., Ferreira M., Condel L. et al. Cellular senescence in aging primates. Science 2006;311(5765):1257. DOI: 10.1126/science.1122446Torres-Guzmán R., Calsina B., Hermoso A. et al. Preclinical characterization of abemaciclib in hormone receptor positive breast cancer. Oncotarget 2017;8:69493–507. DOI: 10.18632/oncotarget.17778Mamedov M. On the 25th anniversary of the discovery of telomerase. Replicative aging of cells: Results of half a century of study. Biomeditsina = Biomedicine 2010;(3):34–8. (In Russ.).Мамедов М. К 25-летию открытия теломеразы. Репликативное старение клеток: итоги полувекового изучения. Биомедицина 2010;(3):34–8.Kovatcheva M., Liu D., Dickson M. MDM2 turnover and expression of ATRX determine the choice between quiescence and senescence in response to CDK4 inhibition. Oncotarget 2015;6(10):8226–43. DOI: 10.18632/oncotarget.3364Faget D.V., Ren Q., Stewart Sh. Unmasking senescence: Context- dependent effects of SASP in cancer. Nat Rev Cancer 2019;19: 439–53. DOI: 10.1038/s41568-019-0156-2Petroni G., Formenti S., Chen-Kiang S. et al. Immunomodulation by anticancer cell cycle inhibitors. Nat Rev Immunol 2020;20: 669–79. DOI: 10.1038/s41577-020-0300-yZhang J., Bu X., Wang H. et al. Cyclin D-CDK4 kinase destabilizes PD-L1 via cullin 3-SPOP to control cancer immune surveillance. Nature 2018;553:91–5. DOI: 10.1038/NATURE25015Laphanuwat P., Jirawatnotai S. Immunomodulatory roles of cell cycle regulators. Front Cell Dev Biol 2019;7:23. DOI: 10.3389/FCELL.2019.00023Chaikovsky A.C., Sage J. Beyond the cell cycle: Enhancing the immune surveillance of tumors via CDK4/6 inhibition. Molecular Cancer Res 2018;16:1454–7. DOI: 10.1158/1541-7786.MCR-18-0201Hortobagyi G. Final iDFS analysis from the NATALEE trial – ribociclib + NSAI as adjuvant treatment in patients with HR+/ HER2– eBC. SABCS 2023. Abstract 12-1-23.Fasching P., Stroyakovskiy D., Yardley D. et al. Adjuvant ribociclib (RIB) plus nonsteroidal aromatase inhibitor (NSAI) in patients (Pts) with HR+/HER2– early breast cancer (EBC): 4-year outcomes from the NATALEE trial. Ann Oncol 2024;35(Suppl 2): 1–72. DOI: 10.1016/j.annonc.2024.08.2251Hurvitz S., Jarzab M., Mateu M.M. et al. Distant disease free survival DDFS across key subgroups from the phase 3 NATALEE trial of ribociclib RIB plus a nonsteroidal aromatase inhibitor NSAI in patients with HR+/HER2– early breast cancer. SABCS 2024. Poster 4-09-22.Hamilton E., Decker T., Rugo H.S. et al. Impact of ribociclib dose reduction on efficacy in patients with hormone receptor positive human epidermal growth factor receptor 2 negative HR+/HER2– early breast cancer EBC in NATALEE. SABCS 2024. Poster 1-11-16.Lüftner D., Banys-Paluchowski M., Hartkopf A.D. et al. Indirect comparison suggests ribociclib combined with non- steroidal aromatase inhibitors is significantly more effective than tamoxifen in premenopausal women with early breast cancer. 19th St.Gallen International Breast Cancer Conference 2025. Poster 014.Li Q., Jiang M., Liu J. et al. Clinicopathologic features, adjuvant treatment patterns and clinical outcomes of HR+/HER2– early breast cancer in China. 19th St.Gallen International Breast Cancer Conference 2025. Poster 265.