Journal of Modern OncologyJournal of Modern OncologyСовременная онкология1815-14341815-1442LLC Obyedinennaya Redaktsiya69726010.26442/18151434.2025.3.203471ArticlesСтатьиReview ArticleFollowing in the footsteps of ASCO-2025: TOP studies that will change the treatment strategy of advanced HR+ and HER2+ breast cancer. A reviewПо следам ASCO-2025: топ исследований, которые изменят стратегию лечения распространенного HR+ и HER2+ рака молочной железыhttps://orcid.org/0000-0002-1124-6802KolyadinaIrina V.КолядинаИрина Владимировна
Russian Federation

D. Sci. (Med.), Prof.

д-р мед. наук, проф., проф. каф. онкологии и паллиативной медицины, вед. науч. сотр.

irinakolyadina@yandex.ruhttps://orcid.org/0000-0002-0995-1801PoddubnayaIrina V.ПоддубнаяИрина Владимировна
Russian Federation

D. Sci. (Med.), Prof., Acad. RAS

акад. РАН, д-р мед. наук, проф., зав. каф. онкологии и паллиативной медицины

irinakolyadina@yandex.ruRussian Medical Academy of Continuous Professional EducationФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава РоссииKulakov National Medical Research Center for Obstetrics, Gynecology and PerinatologyФГБУ «Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии им. акад. В.И. Кулакова» Минздрава России051220252731871970212202502122025Copyright ©; 2025, Consilium MedicumCopyright ©; 2025, ООО "Консилиум Медикум"2025Consilium MedicumООО "Консилиум Медикум"https://creativecommons.org/licenses/by-nc-sa/4.0https://modernonco.orscience.ru/1815-1434/article/view/697260

This review summarizes the six most significant clinical studies on the treatment of advanced hormone-dependent and HER2-positive (HER2+) breast cancer (BC), presented at the ASCO congress in 2025. Among the new data on overcoming hormone resistance, the assessment of overall survival in patients with early relapses with a PIK3CA gene mutation in the INAVO120 study, the idea of a molecular navigation strategy for switching hormonal treatment when an ESR1 gene mutation appears in the randomized clinical trial SERENA-6, as well as a biomarker analysis of the trastuzumab deruxtecan effectiveness in advanced BC with HER2-low/ultralow expression in the randomized clinical trial DESTINY-Breast06 require special attention. For the treatment of patients with advanced HER2+ BC, an analysis of the efficacy and safety of the combination of trastuzumab deruxtecan with pertuzumab in the first line of treatment, the possibility of reintroducing trastuzumab deruxtecan in case of interstitial pneumonitis, as well as a new direction in the treatment of luminal HER2+ variant using the combination of CDK4/6 inhibitors with anti-HER2 therapy, are addressed.

В настоящем обзоре отражены 6 наиболее значимых клинических исследований по лечению распространенного гормонозависимого и HER2-положительного (HER2+) рака молочной железы (РМЖ), представленных на конгрессе ASCO в 2025 г. Среди новых данных по преодолению гормонорезистентности заслуживают особого внимания оценка общей выживаемости у больных с ранними рецидивами с мутацией гена PIK3CA в исследовании INAVO120, идея о молекулярно-навигационной стратегии переключения эндокринотерапии при появлении мутации гена ESR1 в рандомизированном клиническом исследовании SERENA-6, а также биомаркерный анализ эффективности лечения трастузумабом дерукстеканом при распространенном РМЖ с экспрессией HER2-low/ultralow в рандомизированном клиническом исследовании DESTINY-Breast06. Для лечения пациентов с распространенным HER2+ РМЖ будут обсуждены анализ эффективности и безопасности комбинации трастузумаба дерукстекана с пертузумабом в 1-й линии лечения, возможность повторного назначения трастузумаба дерукстекана при развившемся интерстициальном пневмоните, а также новое направление в лечении люминального HER2+ варианта заболевания – комбинация ингибиторов CDK4/6 с анти-HER2-терапией.

ASCO-2025 newshormone-dependent metastatic breast cancerHER2+ metastatic breast cancerovercoming endocrine resistanceearly relapses with PIK3CA gene mutationESR1 gene mutationHER2-low/ultralow expressiontrastuzumab deruxtecanT-DXdrechallenge T-DXd in case ofinterstitial pneumonitisCDK4/6 inhibitors with anti-HER2 therapyновости ASCO-2025гормонозависимый метастатический рак молочной железыHER2+ метастатический рак молочной железыпреодоление эндокринорезистентностиранние рецидивы с мутацией гена PIK3CAмутация гена ESR1экспрессия HER2-low/ultralowтрастузумаб дерукстеканT-DXdповторное назначение трастузумаба дерукстекана при интерстициальном пневмонитеингибиторы CDK4/6 с анти-HER2-терапиейThe paper was prepared with the financial support of the company AstraZeneca. The sponsor was not involved in the data collection and analysis and the interpretation of results. In preparing the manuscript, the authors maintained the independence of opinion.Материал подготовлен при финансовой поддержке компании «АстраЗенека». Спонсор не участвовал в сборе, анализе данных, интерпретации результатов. При подготовке рукописи авторы сохранили независимость мненийTurner NC, Im SA, Saura C, et al. INAVO120: Phase III trial final overall survival (OS) analysis of first-line inavolisib (INAVO)/placebo (PBO) + palbociclib (PALBO) + fulvestrant (FULV) in patients (pts) with PIK3CA-mutated, hormone receptor-positive (HR+), HER2-negative (HER2-), endocrine-resistant advanced breast cancer (aBC). ASCO 2025, Oral Abstract Session #1003. Available at: https://meetings.asco.org/abstracts-presentations/244382. Accessed: 05.08.2025.Turner N, Mayer EL, Park YH, et al. Camizestrant + CDK4/6 inhibitor (CDK4/6i) for the treatment of emergent ESR1 mutations during first-line (1L) endocrine-based therapy (ET) and ahead of disease progression in patients (pts) with HR+/HER2– advanced breast cancer (ABC): Phase 3, double-blind ctDNA-guided SERENA-6 trial. ASCO 2025, Abstract #LBA4. Available at: https://www.asco.org/abstracts-presentations/ABSTRACT487304. Accessed: 05.08.2025.Dent R, Curigliano G, Hu X, et al. Exploratory biomarker analysis of trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy (TPC) in HER2-low/ultralow, hormone receptor-positive (HR+) metastatic breast cancer (mBC) in DESTINY-Breast06 (DB-06). ASCO 2025, Abstract #1013. Available at: https:// www.asco.org/abstracts-presentations/ABSTRACT501216. Accessed: 05.08.2025.Dhillon P, et al. Real-word observational study of patients with endocrine-resistant, hormone HR+ HER2- negative metastatic breast cancer in the first-line setting: patient characreristics, PIK3CA munation prevalence, treatment, and clinical outcomes. SABCS 2024 (Poster P4-07-27).Wang SF, Chou CY, Chao YW, et al. Impact of PIK3CA mutations on the clinical benefits of CDK 4/6 inhibitors in HR+/HER2- advanced breast cancer: An updated pairwise and network meta-analysis. J Cancer. 2025;16(10):3065-79. DOI:10.7150/jca.111362Schagerholm C, Robertson S, Toosi H, et al. PIK3CA mutations in endocrine-resistant breast cancer. Sci Rep. 2024;14(1):12542. DOI:10.1038/s41598-024-62664-1Cortés J, Im SA, Holgado E, et al. The next era of treatment for hormone receptor-positive, HER2-negative advanced breast cancer: Triplet combination-based endocrine therapies. Cancer Treat Rev. 2017;61:53-60. DOI:10.1016/j.ctrv.2017.09.011Jhaveri KL, Im SA, Saura C, et al. Inavolisib or placebo in combination with palbociclib and fulvestrant in patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer: Phase III INAVO120 primary analysis. SABCS 2023. Abstract GS03-13. Available at: https://medically.roche.com/content/dam/pdmahub/restricted/oncology/sabcs-2023/SABCS-2023-presentation-jhaveri-inavolisib-or-placebo-in-combination-with-palbociclib.pdf. Accessed: 05.01.2025.Jhaveri KL, Im SA, Saura C, et al. Overall survival with inavolisib in PIK3CA-mutated advanced breast cancer. N Engl J Med. 2025;393(2):151-61. DOI:10.1056/NEJMoa2501796Goetz MP, Hamilton EP, Campone M, et al. Landscape of baseline and acquired genomic alterations in circulating tumor DNA with abemaciclib alone or with endocrine therapy in advanced breast cancer. Clin Cancer Res. 2024;30(10):2233-44. DOI:10.1158/1078-0432.CCR-22-3573Hortobagyi GN, Stemmer SM, Burris HA, et al. Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer. Ann Oncol. 2018;29(7):1541-7. DOI:10.1093/annonc/mdy155Chaudhary N, Chibly AM, Collier A, et al. CDK4/6i-treated HR+/HER2- breast cancer tumors show higher ESR1 mutation prevalence and more altered genomic landscape. NPJ Breast Cancer. 2024;10(1):15. DOI:10.1038/s41523-024-00617-7Li X, Lu J, Zhang L, et al. Clinical implications of monitoring ESR1 mutations by circulating tumor DNA in estrogen receptor positive metastatic breast cancer: A pilot study. Transl Oncol. 2019;13(2):321-8. DOI:10.1016/j.tranon.2019.11.007Bidard FC, Kaklamani VG, Neven P, et al. Elacestrant (oral selective estrogen receptor degrader) versus standard endocrine therapy for estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: Results from the randomized phase III EMERALD trial. J Clin Oncol. 2022;40(28):3246-56. DOI:10.1200/JCO.22.00338Bhave MA, Quintanilha JCF, Tukachinsky H, et al. Correction: Comprehensive genomic profiling of ESR1, PIK3CA, AKT1, and PTEN in HR(+)HER2(-) metastatic breast cancer: prevalence along treatment course and predictive value for endocrine therapy resistance in real-world practice. Breast Cancer Res Treat. 2024;207(3):611-4. DOI:10.1007/s10549-024-07427-2Oliveira M, Pominchuk D, Nowecki Z, et al. Camizestrant, a next-generation oral SERD, versus fulvestrant in post-menopausal women with oestrogen receptor-positive, HER2-negative advanced breast cancer (SERENA-2): A multi-dose, open-label, randomised, phase 2 trial. Lancet Oncol. 2024;25(11):1424-39. DOI:10.1016/S1470-2045(24)00387-5Bardia A, Hu X, Dent R, et al.; DESTINY-Breast06 Trial Investigators. Trastuzumab deruxtecan after endocrine therapy in metastatic breast cancer. N Engl J Med. 2024;391(22):2110-22. DOI:10.1056/NEJMoa2407086Porter K, Rosenzweig MQ. Current and emerging therapies for HER2-positive women with metastatic breast cancer. J Adv Pract Oncol. 2017;8(2):164-8. PMID:29900024Fenton MA, Tarantino P, Graff SL. Sequencing antibody drug conjugates in breast cancer: Exploring future roles. Curr Oncol. 2023;30(12):10211-23. DOI:10.3390/curroncol30120743Premji SK, O'Sullivan CC. Standard-of-care treatment for HER2+ metastatic breast cancer and emerging therapeutic options. Breast Cancer (Auckl). 2024:18:11782234241234418. DOI:10.1177/11782234241234418Grinda T, Antoine A, Jacot W, et al. Evolution of overall survival and receipt of new therapies by subtype among 20 446 metastatic breast cancer patients in the 2008–2017 ESME cohort. ESMO Open. 2021;6(3):100114. DOI:10.1016/j.esmoop.2021.100114Тюляндин 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 [Tyulandin SA, Artamonova EV, Zhigulev AN, et al. Breast cancer. RUSSCO's Practical Recommendations, Part 1.2. Malignant Tumors. 2024;14(3s2):32-81 (in Russian)]. DOI:10.18027/2224-5057-2024-14-3s2-1.2-01Tolaney SM, Jiang Z, Zhang Q, et al. Trastuzumab deruxtecan (T-DXd) + pertuzumab (P) vs taxane + trastuzumab + pertuzumab (THP) for first-line (1L) treatment of patients (pts) with human epidermal growth factor receptor 2-positive (HER2+) advanced/metastatic breast cancer (a/mBC): Interim results from DESTINY-Breast09. ASCO 2025, Abstract #LBA1008. Available at: https://www.asco.org/abstracts-presentations/ABSTRACT493716. Accessed: 05.08.2025.Natsuhara KH, Blum K, LeVee A, et al. Treatment after trastuzumab-deruxtecan-related interstitial lung disease: A multi-institution cohort study. Rapid Oral Abstract Session, Abstract #1015. Available at: https://meetings.asco.org/abstracts-presentations/253149. Accessed: 05.08.2025.Sohn J, Lim S, Jeong JH, et al. Phase IB and II study of ribociclib with trastuzumab plus endocrine therapy in HR+/ HER2+ advanced breast cancer patients: Korean Cancer Study Group BR 18-2 MINI trial. Rapid Oral Abstract Session, Abstract #1016. Available at: https://meetings.asco.org/abstracts-presentations/244389. Accessed: 05.08.2025.Rugo HS, Bianchini G, Cortes J, et al. Optimizing treatment management of trastuzumab deruxtecan in clinical practice of breast cancer. ESMO Open. 2022;7(4):100553. DOI:10.1016/j.esmoop.2022.100553Rugo HS, Crossno CL, Gesthalter YB, et al. Real-world perspectives and practices for pneumonitis/interstitial lung disease associated with trastuzumab deruxtecan use in human epidermal growth factor receptor 2-expressing metastatic breast cancer. JCO Oncol Pract. 2023;19(8):539-46. DOI:10.1200/OP.22.00480Natsuhara KH, Blum K, LeVee A, et al. Treatment rechallenge after trastuzumabderuxtecan-related interstitial lung disease: A multi-institution cohort study. J Clin Oncol. 2025;43(Suppl. 16). DOI:10.1200/JCO.2025.43.16_suppl.1015Tolaney SM, Goel S, Nadal J, et al. Overall survival and exploratory biomarker analyses of abemaciclib plus trastuzumab with or without fulvestrant versus trastuzumab plus chemotherapy in HR+, HER2+ metastatic breast cancer patients. Clin Cancer Res. 2023;30(1):39-49. DOI:10.1158/1078-0432.CCR-23-1209Loibl S, Metzger O, Mandrekar SJ, et al. PATINA: A randomized, open label, phase III trial to evaluate the efficacy and safety of palbociclib 1 Anti-HER2 therapy 1 endocrine therapy (ET) vs. anti-HER2 therapy 1 ET after induction treatment for hormone receptor positive (HR1)/HER2-positive metastatic breast cancer (MBC). Ann Oncol. 2018;29(Suppl. 8): viii121. DOI:10.1093/annonc/mdy272