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Эффективность неоадъювантной терапии в режиме TCHP у пациенток с ранним HER2-позитивным раком молочной железы при добавлении эмпэгфилграстима: финальный анализ исследования DEFENDOR SPECIAL, когорта HER2+ РМЖ
Эффективность неоадъювантной терапии в режиме TCHP у пациенток с ранним HER2-позитивным раком молочной железы при добавлении эмпэгфилграстима: финальный анализ исследования DEFENDOR SPECIAL, когорта HER2+ РМЖ
Жукова Л.Г., Ибрагимова Т.М., Филоненко Д.А., Ганьшина И.П., Сорокина И.В., Лазарев А.А., Мироненко О.Н., Просяникова О.Н. Эффективность неоадъювантной терапии в режиме TCHP у пациенток с ранним HER2-позитивным раком молочной железы при добавлении эмпэгфилграстима: финальный анализ исследования DEFENDOR SPECIAL, когорта HER2+ РМЖ. Современная Онкология. 2026;28(1):21–29. DOI: 10.26442/18151434.2026.1.203640
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Аннотация
Обоснование. Исследование DEFENDOR SPECIAL (NCT04905329) проведено с целью оценки эффективности и безопасности комбинированной химиотерапии в сочетании с первичной профилактикой нейтропении эмпэгфилграстимом у пациенток с различными злокачественными новообразованиями, имеющих высокий риск рецидива. В статье представлен анализ результатов исследования, инициированного исследователями, по оценке эффективности и безопасности эмпэгфилграстима (Экстимия®) у пациенток с HER2-позитивным раком молочной железы (HER2+ РМЖ)) II–III стадий, получавших неоадъювантную терапию (НАТ) в режиме TCHP.
Цель. Оценка клинической эффективности и безопасности пролонгированного гранулоцитарного колониестимулирующего фактора эмпэгфилграстим у пациенток с ранним HER2+ РМЖ, получавших НАТ в режиме TCHP.
Материалы и методы. В анализ включены данные 105 пациенток. Всем женщинам для первичной профилактики фебрильной нейтропении (ФН) вводили подкожно эмпэгфилграстим в дозе 7,5 мг однократно на курс. Первичная конечная точка – относительная дозоинтенсивность проведенных курсов НАТ, вторичные конечные точки включали частоту полной патоморфологической регрессии (pCR), уровень остаточной резидуальной опухоли (RCB) и частоту нежелательных явлений. Проведено сравнение частот pCR в данном исследовании и во внешней контрольной группе пациенток с ранним HER2+ РМЖ клинической стадии cT2–cT4/cN0–cN3/cM0, которые с апреля 2020 по сентябрь 2023 г. получали НАТ в режиме TCHP с профилактикой ФН филграстимом в ГБУЗ «МКНЦ им. А.С. Логинова». Выравнивание по исходным характеристикам проводили методом полного мэтчинга по расстоянию Махаланобиса.
Результаты. В исследовании DEFENDOR SPECIAL медиана (Q1–Q3) возраста составила 53 (43–61) года, медиана (Q1–Q3) относительной дозоинтенсивности – 97,1% (76,8–104,9). У 72,5% (76/105) пациенток достигнута pCR, у 7/105 (6,6%) и 16/105 (15,2%) наблюдали RCB-I и RCB-II соответственно. Наиболее высокая частота pCR отмечена у пациенток с гормонорезистентным (HR-) HER2+ (3+) – 85,3% (29/34). Не зарегистрировано ни одного случая ФН. Нейтропению III–IV степени наблюдали у 2,9% (3/105) пациенток, тромбоцитопению I–II степени – у 34,3% (36/105), III степени – у 1,0% (1/105). Шанс достижения pCR при применении эмпэгфилграстима был статистически значимо выше по сравнению с филграстимом: скорректированное отношение шансов составило 1,73 (95% доверительный интервал 1,04–2,89; p=0,0357).
Заключение. Первичная профилактика ФН с применением эмпэгфилграстима обеспечивает значимое преимущество в достижении pCR по сравнению с филграстимом у пациенток с ранним HER2+ РМЖ в неоадъювантном режиме TCHP.
Ключевые слова: HER2-позитивный рак молочной железы, относительная дозоинтенсивность, полная патоморфологическая регрессия опухоли, гранулоцитарный колониестимулирующий фактор, эмпэгфилграстим, филграстим, фебрильная нейтропения, тромбоцитопения, остаточная опухоль
Aim. To assess the clinical efficacy and safety of prolonged granulocyte colony-stimulating factor empegfilgrastim in patients with early HER2+ BCG treated with NAT as part of the TCHP regimen.
Materials and methods. Data from 105 patients were analyzed. For the primary prevention of febrile neutropenia (FN), all patients received subcutaneous empegfilgrastim at a dose of 7.5 mg once per course. The primary endpoint was the relative dose intensity of the NAT courses, and the secondary endpoints included the complete pathomorphologic regression (pCR) rate, residual cancer burden (RCB), and adverse event rate. Comparison of pCR rates in this study and in the external control group of patients with early HER2+ BC of the clinical stage cT2-cT4/cN0-cN3/cM0, who received NAT in the TCHP regimen with filgrastim for the FN prevention from April 2020 to September 2023 at the Loginov Moscow Clinical Scientific Center. The matching based on the initial characteristics was performed using complete matching with the Mahalanobis distance.
Results. In the DEFENDOR SPECIAL study, the median age (Q1–Q3) was 53 (43–61) years. The median relative dose intensity (Q1–Q3) was 97.1% (76.8–104.9%). PCR was achieved in 72.5% (76/105) of patients, while RCB-I and RCB-II were observed in 6.6% (7/105) and 15.2% (16/105), respectively. The highest pCR rate was observed in patients with HR-negative/HER2-positive (3+) tumors at 85.3% (29/34). No FN events were reported. Grade III–IV neutropenia occurred in 2.9% (3/105) of patients, grade I–II thrombocytopenia in 34.3% (36/105), and grade III thrombocytopenia in 1.0% (1/105). The probability of achieving pCR with empegfilgrastim was statistically significantly higher compared to filgrastim, with an adjusted odds ratio of 1.73 (95% confidence interval 1.04–2.89; p=0.0357).
Conclusion. Primary prevention of FN with empegfilgrastim offers a significant advantage in achieving pCR compared to filgrastim in patients with early HER2-positive breast cancer receiving a neoadjuvant TCHP regimen.
Keywords: HER2-positive breast cancer, relative dose intensity, complete pathomorphological tumor regression, granulocyte colony-stimulating factor, empegfilgrastim, filgrastim, febrile neutropenia, thrombocytopenia, residual tumor
Цель. Оценка клинической эффективности и безопасности пролонгированного гранулоцитарного колониестимулирующего фактора эмпэгфилграстим у пациенток с ранним HER2+ РМЖ, получавших НАТ в режиме TCHP.
Материалы и методы. В анализ включены данные 105 пациенток. Всем женщинам для первичной профилактики фебрильной нейтропении (ФН) вводили подкожно эмпэгфилграстим в дозе 7,5 мг однократно на курс. Первичная конечная точка – относительная дозоинтенсивность проведенных курсов НАТ, вторичные конечные точки включали частоту полной патоморфологической регрессии (pCR), уровень остаточной резидуальной опухоли (RCB) и частоту нежелательных явлений. Проведено сравнение частот pCR в данном исследовании и во внешней контрольной группе пациенток с ранним HER2+ РМЖ клинической стадии cT2–cT4/cN0–cN3/cM0, которые с апреля 2020 по сентябрь 2023 г. получали НАТ в режиме TCHP с профилактикой ФН филграстимом в ГБУЗ «МКНЦ им. А.С. Логинова». Выравнивание по исходным характеристикам проводили методом полного мэтчинга по расстоянию Махаланобиса.
Результаты. В исследовании DEFENDOR SPECIAL медиана (Q1–Q3) возраста составила 53 (43–61) года, медиана (Q1–Q3) относительной дозоинтенсивности – 97,1% (76,8–104,9). У 72,5% (76/105) пациенток достигнута pCR, у 7/105 (6,6%) и 16/105 (15,2%) наблюдали RCB-I и RCB-II соответственно. Наиболее высокая частота pCR отмечена у пациенток с гормонорезистентным (HR-) HER2+ (3+) – 85,3% (29/34). Не зарегистрировано ни одного случая ФН. Нейтропению III–IV степени наблюдали у 2,9% (3/105) пациенток, тромбоцитопению I–II степени – у 34,3% (36/105), III степени – у 1,0% (1/105). Шанс достижения pCR при применении эмпэгфилграстима был статистически значимо выше по сравнению с филграстимом: скорректированное отношение шансов составило 1,73 (95% доверительный интервал 1,04–2,89; p=0,0357).
Заключение. Первичная профилактика ФН с применением эмпэгфилграстима обеспечивает значимое преимущество в достижении pCR по сравнению с филграстимом у пациенток с ранним HER2+ РМЖ в неоадъювантном режиме TCHP.
Ключевые слова: HER2-позитивный рак молочной железы, относительная дозоинтенсивность, полная патоморфологическая регрессия опухоли, гранулоцитарный колониестимулирующий фактор, эмпэгфилграстим, филграстим, фебрильная нейтропения, тромбоцитопения, остаточная опухоль
________________________________________________
Aim. To assess the clinical efficacy and safety of prolonged granulocyte colony-stimulating factor empegfilgrastim in patients with early HER2+ BCG treated with NAT as part of the TCHP regimen.
Materials and methods. Data from 105 patients were analyzed. For the primary prevention of febrile neutropenia (FN), all patients received subcutaneous empegfilgrastim at a dose of 7.5 mg once per course. The primary endpoint was the relative dose intensity of the NAT courses, and the secondary endpoints included the complete pathomorphologic regression (pCR) rate, residual cancer burden (RCB), and adverse event rate. Comparison of pCR rates in this study and in the external control group of patients with early HER2+ BC of the clinical stage cT2-cT4/cN0-cN3/cM0, who received NAT in the TCHP regimen with filgrastim for the FN prevention from April 2020 to September 2023 at the Loginov Moscow Clinical Scientific Center. The matching based on the initial characteristics was performed using complete matching with the Mahalanobis distance.
Results. In the DEFENDOR SPECIAL study, the median age (Q1–Q3) was 53 (43–61) years. The median relative dose intensity (Q1–Q3) was 97.1% (76.8–104.9%). PCR was achieved in 72.5% (76/105) of patients, while RCB-I and RCB-II were observed in 6.6% (7/105) and 15.2% (16/105), respectively. The highest pCR rate was observed in patients with HR-negative/HER2-positive (3+) tumors at 85.3% (29/34). No FN events were reported. Grade III–IV neutropenia occurred in 2.9% (3/105) of patients, grade I–II thrombocytopenia in 34.3% (36/105), and grade III thrombocytopenia in 1.0% (1/105). The probability of achieving pCR with empegfilgrastim was statistically significantly higher compared to filgrastim, with an adjusted odds ratio of 1.73 (95% confidence interval 1.04–2.89; p=0.0357).
Conclusion. Primary prevention of FN with empegfilgrastim offers a significant advantage in achieving pCR compared to filgrastim in patients with early HER2-positive breast cancer receiving a neoadjuvant TCHP regimen.
Keywords: HER2-positive breast cancer, relative dose intensity, complete pathomorphological tumor regression, granulocyte colony-stimulating factor, empegfilgrastim, filgrastim, febrile neutropenia, thrombocytopenia, residual tumor
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Список литературы
1. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229-63. DOI:10.3322/caac.21834
2. Pauletti G, Dandekar S, Rong H, et al. Assessment of methods for tissue-based detection of the HER-2/neu alteration in human breast cancer: a direct comparison of fluorescence in situ hybridization and immunohistochemistry. J Clin Oncol. 2000;18(21):3651-64. DOI:10.1200/JCO.2000.18.21.3651
3. Gradishar WJ, Moran MS, Abraham J, et al. NCCN Guidelines® Insights: Breast Cancer, Version 5.2025. J Natl Compr Canc Netw. 2025;23(11):426-36. DOI:10.6004/jnccn.2025.0053
4. Broglio KR, Quintana M, Foster M, et al. Association of Pathologic Complete Response to Neoadjuvant Therapy in HER2-Positive Breast Cancer With Long-Term Outcomes: A Meta-Analysis. JAMA Oncol. 2016;2(6):751-60. DOI:10.1001/jamaoncol.2015.6113
5. Hall BJ, Bhojwani AA, Wong H, et al. Neoadjuvant Trastuzumab and Pertuzumab for Early HER2-Positive Breast Cancer: A Real World Experience. Breast J. 2022;2022:7146172. DOI:10.1155/2022/7146172
6. Zhou M, Wang S, Wan N, et al. Efficacy and safety of neoadjuvant pertuzumab plus trastuzumab in combination with chemotherapy regimen in Chinese patients with HER2-positive early breast cancer: a real-world retrospective multi-center cohort study. Ann Transl Med. 2022;10(24):1387. DOI:10.21037/atm-22-6054
7. Conte P, Schneeweiss A, Loibl S, et al. Patient-reported outcomes from KATHERINE: A phase 3 study of adjuvant trastuzumab emtansine versus trastuzumab in patients with residual invasive disease after neoadjuvant therapy for human epidermal growth factor receptor 2-positive breast cancer. Cancer. 2020;126(13):3132-9. DOI:10.1002/cncr.32873
8. Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384(9938):164-72. DOI:10.1016/S0140-6736(13)62422-8
9. Davey MG, Browne F, Miller N, et al. Pathological complete response as a surrogate to improved survival in human epidermal growth factor receptor-2-positive breast cancer: systematic review and meta-analysis. BJS Open. 2022;6(3):zrac028.
10. Iorio MD, Elliott MJ, Scott JL, et al. Real-world outcomes of patients with human epidermal growth factor 2 (HER2)-positive breast cancer receiving neoadjuvant therapy without adjuvant ado-trastuzumab emtansine (T-DM1). J Clin Oncol. 2022;40(Suppl. 16):584. DOI:10.1200/JCO.2022.40. 16_suppl.584
11. Loibl S, André F, Bachelot T, et al. Early breast cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024;35(2):159-82. DOI:10.1016/j.annonc.2023.11.016
12. Sun HK, Jiang WL, Zhang SL, et al. Predictive value of tumor-infiltrating lymphocytes for neoadjuvant therapy response in triple-negative breast cancer: A systematic review and meta-analysis. World J Clin Oncol. 2024;15(7):920-35. DOI:10.5306/wjco.v15.i7.920
13. Finkelman BS, Zhang H, Hicks DG, et al. Tumor infiltrating lymphocytes in breast cancer: A narrative review with focus on analytic validity, clinical validity, and clinical utility. Hum Pathol. 2025;162:105866. DOI:10.1016/j.humpath.2025.105866
14. Zakaria D, Feuerhake F, Garke M, et al. Impact of tumor-infiltrating lymphocytes (TILs) on the pathological complete response (pCR) after neoadjuvant chemotherapy in triple-negative and HER2-positive breast cancer. ESMO Open. 2025
15. Denkert C, von Minckwitz G, Darb-Esfahani S, et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol. 2018;19(1):40-50. DOI:10.1016/S1470-2045(17)30904-X
16. de Jong VMT, Wang Y, Ter Hoeve ND, et al. Prognostic Value of Stromal Tumor-Infiltrating Lymphocytes in Young, Node-Negative, Triple-Negative Breast Cancer Patients Who Did Not Receive (neo)Adjuvant Systemic Therapy. J Clin Oncol. 2022;40(21):2361-74. DOI:10.1200/JCO.21.01536
17. Tsao LC, Crosby EJ, Trotter TN, et al. Trastuzumab/pertuzumab combination therapy stimulates antitumor responses through complement-dependent cytotoxicity and phagocytosis. JCI Insight. 2022;7(6):e155636. DOI:10.1172/jci.insight.155636
18. Kınıkoğlu O, Altıntaş YE, Yıldız A, et al. Tumor-infiltrating lymphocytes as predictive biomarkers in neoadjuvant treatment of HER2-positive breast cancer. Oncologist. 2025;30(4):oyaf054. DOI:10.1093/oncolo/oyaf054
19. Karagiannidis I, Salataj E, Said Abu Egal E, Beswick EJ. G-CSF in tumors: Aggressiveness, tumor microenvironment and immune cell regulation. Cytokine. 2021;142:155479. DOI:10.1016/j.cyto.2021.155479
20. Eruslanov EB, Bhojnagarwala PS, Quatromoni JG, et al. Tumor-associated neutrophils stimulate T cell responses in early-stage human lung cancer. J Clin Invest. 2014;124(12):5466-80. DOI:10.1172/JCI77053
21. Singhal S, Bhojnagarwala PS, O'Brien S, et al. Origin and Role of a Subset of Tumor-Associated Neutrophils with Antigen-Presenting Cell Features in Early-Stage Human Lung Cancer. Cancer Cell. 2016;30(1):120-35. DOI:10.1016/j.ccell.2016.06.001
22. Снеговой А.В., Кононенко И.Б., Радюкова И.М., и др. Эффективность и безопасность применения препарата эмпэгфилграстим (Экстимия®) у пациентов с солидными опухолями, получающих цитотоксическую терапию: финальные результаты исследования DEFENDOR. Современная Онкология. 2024;26(2):159-71 [Snegovoy AV, Kononenko IB, Radiukova IM, et al. Effectiveness and safety of empegfilgrastim (Extimia®) in patients with solid tumors receiving cytotoxic therapy: final results of the DEFENDOR study. Journal of Modern Oncology. 2024;26(2):159-71 (in Russian)]. DOI:10.26442/18151434.2024.2.202829
23. Zhukova L, Ibragimova T, Filonenko D, et al. DEFENDOR SPECIAL: Effect of primary prophylaxis with empegfilgrastim on pCR rate after neoadjuvant TCHP in early HER2+ breast cancer patients – Matching-adjusted indirect comparison (MAIC). J Clin Oncol. 2025;43(Suppl. 16). DOI:10.1200/JCO.2025.43.16_suppl.e13011
24. Tryakin A, Dinaeva E, Fedyanin M, et al. 1865P DEFENDOR special: Real-world use of pegylated granulocyte-colony stimulating factor in patients with gastrointestinal cancers. Annals of Oncology. 2024;35:S1096. DOI:10.1016/j.annonc.2024.08.1959
25. Нестерова Е.C., Сайдуллаева А.Ф., Шерстнев Д.Г., и др. Эффективность и безопасность применения препарата эмпэгфилграстим (Экстимия®, БИОКАД) у пациентов с лимфопролиферативными заболеваниями, получающих цитотоксическую терапию: результаты многоцентрового ретроспективно-проспективного наблюдательного пострегистрационного исследования LEGERITY. Современная Онкология. 2023;25(4):80-8 [Nesterova ES, Saydullaeva AF, Sherstnev DG, et al. Effectiveness and safety of empegfilgrastim (Extimia®, BIOCAD) in patients with lymphoproliferative diseases who receive cytotoxic therapy: results of LEGERITY, the second interim analysis of multicenter retrospective-and-prospective observational post-marketing study. Journal of Modern Oncology. 2022;24(1):80-8 (in Russian)]. DOI:10.26442/18151434.2022.1.201493
26. Спорник А.А, Васильев Н.С., Самойлова А.А., и др. Первичная профилактика нейтропении эмпэгфилграстимом у пациентов с распространенными стадиями классической лимфомы Ходжкина, получавших интенсивную химиотерапию первой линии по модифицированной программе 6 циклов EACODD-14 в рамках протокола «ЛХ-Россия-1». Клиническая онкогематология. 2023;16(4):370-9 [Spornik AA, Vasilev NS, Samoilova AA, et al. Primary prevention of neutropenia by empegfilgrastim in patients with advanced stages of classical hodgkin lymphoma treated with intensive first-line chemotherapy with a modified 6-cycle program EACODD-14 under the protocol “LKh-Rossiya-1”. Clinical Oncohematology. 2023;16(4):370-9 (in Russian)]. DOI:10.21320/2500-2139-2023-16-4-370-379
27. Кремнева Н.В., Дудина Г.А., Тагиева Э.У., и др. Применение гранулоцитарных колониестимулирующих факторов у пациентов с ВИЧ-ассоциированными лимфопролиферативными заболеваниями, получающих цитотоксическую терапию: опыт исследовательского центра. Современная Онкология. 2025;26(4):468-72 [Kremneva NV, Dudina GA, Tagieva EU, et al. Use of granulocyte colony-stimulating factors in patients with HIV-associated lymphoproliferative diseases receiving cytotoxic therapy: Experience of a research center. Journal of Modern Oncology. 2025;26(4):468-72 (in Russian)]. DOI:10.26442/18151434.2024.4.203111
28. Чапко Я.С., Дубовиченко Д.М., Ружникова А.А., и др. Применение препарата эмпэгфилграстим для первичной профилактики фебрильной нейтропении у пациентов, получающих миелосупрессивную терапию. Опыт Архангельского клинического онкологического диспансера. Поддерживающая терапия в онкологии. 2024;1(2):23-31 [Chapko YaS, Dubovichenko DM, Ruzhnikova AA, et al. Use of empegfilgrastim for primary prevention of febrile neutropenia in patients receiving myelosuppressive therapy. Experience of the Arkhangelsk Clinical Oncological Dispensary. Podderzhivayushchaya terapiya v onkologii = Supportive Therapy in Oncology. 2024;1(2):23-31 (in Russian)]. DOI:10.17650/3034-2473-2024-1-2-23-31
29. Саевец В.В., Кузьмин Н.К., Шаманова А.Ю., и др. Экономическая эффективность применения гранулоцитарного колониестимулирующего фактора при лечении лейомиосарком тела матки. Современная Онкология. 2024;26(3):335-40 [Saevets VV, Kuzmin NK, Shamanova AY, et al. Cost-effectiveness of using granulocyte colony-stimulating factor in the treatment of uterine body leiomyosarcomas. A retrospective analysis. Journal of Modern Oncology. 2024;26(3):335-40 (in Russian)]. DOI:10.26442/18151434.2024.3.203011
30. Нестерова Е.С., Мангасарова Я.К., Багова М.О., и др. Оценка эффективности мобилизации гемопоэтических стволовых клеток крови с применением препарата эмпэгфилграстим (Экстимия®, АО «Биокад») у больных лимфопролиферативными заболеваниями: опыт нескольких центров на территории Российской Федерации. Современная Онкология. 2024;26(3):323-34 [Nesterova ES, Mangasarova JK, Bagova MO, et al. Evaluation of the effectiveness of hematopoietic blood stem cell mobilization using empegfilgrastim (Extimia®, BIOCAD) in patients with lymphoproliferative diseases: the experience of several centers in the Russian Federation. A retrospective study. Journal of Modern Oncology. 2024;26(3):323-34 (in Russian)]. DOI:10.26442/18151434.2024.3.202989
31. Salgado R, Denkert C, Demaria S, et al. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol. 2015;26(2):259-71. DOI:10.1093/annonc/mdu450
32. Gianni L, Pienkowski T, Im YH, et al. 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial. Lancet Oncol. 2016;17(6):791-800. DOI:10.1016/S1470-2045(16)00163-7
33. Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13(1):25-32. DOI:10.1016/S1470-2045(11)70336-9
34. Shao Z, Pang D, Yang H, et al. Efficacy, Safety, and Tolerability of Pertuzumab, Trastuzumab, and Docetaxel for Patients With Early or Locally Advanced ERBB2-Positive Breast Cancer in Asia: The PEONY Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020;6(3):e193692. DOI:10.1001/jamaoncol.2019.3692
35. Schneeweiss A, Chia S, Hickish T, et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013;24(9):2278-84. DOI:10.1093/annonc/mdt182
36. Swain SM, Ewer MS, Viale G, et al. Pertuzumab, trastuzumab, and standard anthracycline- and taxane-based chemotherapy for the neoadjuvant treatment of patients with HER2-positive localized breast cancer (BERENICE): a phase II, open-label, multicenter, multinational cardiac safety study. Ann Oncol. 2018;29(3):646-53. DOI:10.1093/annonc/mdx773
37. Nitz UA, Gluz O, Christgen M, et al. De-escalation strategies in HER2-positive early breast cancer (EBC): final analysis of the WSG-ADAPT HER2+/HR- phase II trial: efficacy, safety, and predictive markers for 12 weeks of neoadjuvant dual blockade with trastuzumab and pertuzumab ± weekly paclitaxel. Ann Oncol. 2017;28(11):2768-72. DOI:10.1093/annonc/mdx494
38. Hurvitz SA, Martin M, Symmans WF, et al. Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2018;19(1):115-26. DOI:10.1016/S1470-2045(17)30716-7
39. Singh JC, Mamtani A, Barrio A, et al. Pathologic Complete Response with Neoadjuvant Doxorubicin and Cyclophosphamide Followed by Paclitaxel with Trastuzumab and Pertuzumab in Patients with HER2-Positive Early Stage Breast Cancer: A Single Center Experience. Oncologist. 2017;22(2):139-43. DOI:10.1634/theoncologist.2016-0268
40. Thaler S, Schmidt M, Roβwag S, et al. Proteasome inhibitors prevent bi-directional HER2/estrogen-receptor cross-talk leading to cell death in endocrine and lapatinib-resistant HER2+/ER+ breast cancer cells. Oncotarget. 2017;8(42):72281-301. DOI:10.18632/oncotarget.20261
41. Chen HL, Chen Q, Deng YC. Pathologic complete response to neoadjuvant anti-HER2 therapy is associated with HER2 immunohistochemistry score in HER2-positive early breast cancer. Medicine (Baltimore). 2021;100(44):e27632. DOI:10.1097/MD.0000000000027632
42. Gilbar P, McPherson I, Sorour N, et al. High incidence of febrile neutropenia following adjuvant breast chemotherapy with docetaxel, carboplatin and trastuzumab. Breast Cancer Manage. 2014;3(4):327-333. DOI:10.2217/bmt.14.22
43. Cavalloni G, Sarotto I, Pignochino Y, et al. Granulocyte-colony stimulating factor upregulates ErbB2 expression on breast cancer cell lines and converts primary resistance to trastuzumab. Anticancer Drugs. 2008;19(7):689-96. DOI:10.1097/CAD.0b013e3283050083
44. Gruosso T, Gigoux M, Manem VSK, et al. Spatially distinct tumor immune microenvironments stratify triple-negative breast cancers. J Clin Invest. 2019;129(4):1785-800. DOI:10.1172/JCI96313
45. Wang XQ, Danenberg E, Huang CS, et al. Spatial predictors of immunotherapy response in triple-negative breast cancer. Nature. 2023;621(7980):868-76. DOI:10.1038/s41586-023-06498-3
46. Denkert C. The immunogenicity of breast cancer--molecular subtypes matter. Ann Oncol. 2014;25(8):1453-5. DOI:10.1093/annonc/mdu235
47. Liefaard MC, van der Voort A, van Seijen M, et al. Tumor-infiltrating lymphocytes in HER2-positive breast cancer treated with neoadjuvant chemotherapy and dual HER2-blockade. NPJ Breast Cancer. 2024;10(1):29. DOI:10.1038/s41523-024-00636-4
48. Xu L, Saunders K, Huang SP, et al. A comprehensive single-cell breast tumor atlas defines epithelial and immune heterogeneity and interactions predicting anti-PD-1 therapy response. Cell Rep Med. 2024;5(5):101511. DOI:10.1016/j.xcrm.2024.10151
2. Pauletti G, Dandekar S, Rong H, et al. Assessment of methods for tissue-based detection of the HER-2/neu alteration in human breast cancer: a direct comparison of fluorescence in situ hybridization and immunohistochemistry. J Clin Oncol. 2000;18(21):3651-64. DOI:10.1200/JCO.2000.18.21.3651
3. Gradishar WJ, Moran MS, Abraham J, et al. NCCN Guidelines® Insights: Breast Cancer, Version 5.2025. J Natl Compr Canc Netw. 2025;23(11):426-36. DOI:10.6004/jnccn.2025.0053
4. Broglio KR, Quintana M, Foster M, et al. Association of Pathologic Complete Response to Neoadjuvant Therapy in HER2-Positive Breast Cancer With Long-Term Outcomes: A Meta-Analysis. JAMA Oncol. 2016;2(6):751-60. DOI:10.1001/jamaoncol.2015.6113
5. Hall BJ, Bhojwani AA, Wong H, et al. Neoadjuvant Trastuzumab and Pertuzumab for Early HER2-Positive Breast Cancer: A Real World Experience. Breast J. 2022;2022:7146172. DOI:10.1155/2022/7146172
6. Zhou M, Wang S, Wan N, et al. Efficacy and safety of neoadjuvant pertuzumab plus trastuzumab in combination with chemotherapy regimen in Chinese patients with HER2-positive early breast cancer: a real-world retrospective multi-center cohort study. Ann Transl Med. 2022;10(24):1387. DOI:10.21037/atm-22-6054
7. Conte P, Schneeweiss A, Loibl S, et al. Patient-reported outcomes from KATHERINE: A phase 3 study of adjuvant trastuzumab emtansine versus trastuzumab in patients with residual invasive disease after neoadjuvant therapy for human epidermal growth factor receptor 2-positive breast cancer. Cancer. 2020;126(13):3132-9. DOI:10.1002/cncr.32873
8. Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384(9938):164-72. DOI:10.1016/S0140-6736(13)62422-8
9. Davey MG, Browne F, Miller N, et al. Pathological complete response as a surrogate to improved survival in human epidermal growth factor receptor-2-positive breast cancer: systematic review and meta-analysis. BJS Open. 2022;6(3):zrac028.
10. Iorio MD, Elliott MJ, Scott JL, et al. Real-world outcomes of patients with human epidermal growth factor 2 (HER2)-positive breast cancer receiving neoadjuvant therapy without adjuvant ado-trastuzumab emtansine (T-DM1). J Clin Oncol. 2022;40(Suppl. 16):584. DOI:10.1200/JCO.2022.40. 16_suppl.584
11. Loibl S, André F, Bachelot T, et al. Early breast cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024;35(2):159-82. DOI:10.1016/j.annonc.2023.11.016
12. Sun HK, Jiang WL, Zhang SL, et al. Predictive value of tumor-infiltrating lymphocytes for neoadjuvant therapy response in triple-negative breast cancer: A systematic review and meta-analysis. World J Clin Oncol. 2024;15(7):920-35. DOI:10.5306/wjco.v15.i7.920
13. Finkelman BS, Zhang H, Hicks DG, et al. Tumor infiltrating lymphocytes in breast cancer: A narrative review with focus on analytic validity, clinical validity, and clinical utility. Hum Pathol. 2025;162:105866. DOI:10.1016/j.humpath.2025.105866
14. Zakaria D, Feuerhake F, Garke M, et al. Impact of tumor-infiltrating lymphocytes (TILs) on the pathological complete response (pCR) after neoadjuvant chemotherapy in triple-negative and HER2-positive breast cancer. ESMO Open. 2025
15. Denkert C, von Minckwitz G, Darb-Esfahani S, et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol. 2018;19(1):40-50. DOI:10.1016/S1470-2045(17)30904-X
16. de Jong VMT, Wang Y, Ter Hoeve ND, et al. Prognostic Value of Stromal Tumor-Infiltrating Lymphocytes in Young, Node-Negative, Triple-Negative Breast Cancer Patients Who Did Not Receive (neo)Adjuvant Systemic Therapy. J Clin Oncol. 2022;40(21):2361-74. DOI:10.1200/JCO.21.01536
17. Tsao LC, Crosby EJ, Trotter TN, et al. Trastuzumab/pertuzumab combination therapy stimulates antitumor responses through complement-dependent cytotoxicity and phagocytosis. JCI Insight. 2022;7(6):e155636. DOI:10.1172/jci.insight.155636
18. Kınıkoğlu O, Altıntaş YE, Yıldız A, et al. Tumor-infiltrating lymphocytes as predictive biomarkers in neoadjuvant treatment of HER2-positive breast cancer. Oncologist. 2025;30(4):oyaf054. DOI:10.1093/oncolo/oyaf054
19. Karagiannidis I, Salataj E, Said Abu Egal E, Beswick EJ. G-CSF in tumors: Aggressiveness, tumor microenvironment and immune cell regulation. Cytokine. 2021;142:155479. DOI:10.1016/j.cyto.2021.155479
20. Eruslanov EB, Bhojnagarwala PS, Quatromoni JG, et al. Tumor-associated neutrophils stimulate T cell responses in early-stage human lung cancer. J Clin Invest. 2014;124(12):5466-80. DOI:10.1172/JCI77053
21. Singhal S, Bhojnagarwala PS, O'Brien S, et al. Origin and Role of a Subset of Tumor-Associated Neutrophils with Antigen-Presenting Cell Features in Early-Stage Human Lung Cancer. Cancer Cell. 2016;30(1):120-35. DOI:10.1016/j.ccell.2016.06.001
22. Snegovoy AV, Kononenko IB, Radiukova IM, et al. Effectiveness and safety of empegfilgrastim (Extimia®) in patients with solid tumors receiving cytotoxic therapy: final results of the DEFENDOR study. Journal of Modern Oncology. 2024;26(2):159-71 (in Russian). DOI:10.26442/18151434.2024.2.202829
23. Zhukova L, Ibragimova T, Filonenko D, et al. DEFENDOR SPECIAL: Effect of primary prophylaxis with empegfilgrastim on pCR rate after neoadjuvant TCHP in early HER2+ breast cancer patients – Matching-adjusted indirect comparison (MAIC). J Clin Oncol. 2025;43(Suppl. 16). DOI:10.1200/JCO.2025.43.16_suppl.e13011
24. Tryakin A, Dinaeva E, Fedyanin M, et al. 1865P DEFENDOR special: Real-world use of pegylated granulocyte-colony stimulating factor in patients with gastrointestinal cancers. Annals of Oncology. 2024;35:S1096. DOI:10.1016/j.annonc.2024.08.1959
25. Nesterova ES, Saydullaeva AF, Sherstnev DG, et al. Effectiveness and safety of empegfilgrastim (Extimia®, BIOCAD) in patients with lymphoproliferative diseases who receive cytotoxic therapy: results of LEGERITY, the second interim analysis of multicenter retrospective-and-prospective observational post-marketing study. Journal of Modern Oncology. 2022;24(1):80-8 (in Russian). DOI:10.26442/18151434.2022.1.201493
26. Spornik AA, Vasilev NS, Samoilova AA, et al. Primary prevention of neutropenia by empegfilgrastim in patients with advanced stages of classical hodgkin lymphoma treated with intensive first-line chemotherapy with a modified 6-cycle program EACODD-14 under the protocol “LKh-Rossiya-1”. Clinical Oncohematology. 2023;16(4):370-9 (in Russian). DOI:10.21320/2500-2139-2023-16-4-370-379
27. Kremneva NV, Dudina GA, Tagieva EU, et al. Use of granulocyte colony-stimulating factors in patients with HIV-associated lymphoproliferative diseases receiving cytotoxic therapy: Experience of a research center. Journal of Modern Oncology. 2025;26(4):468-72 (in Russian). DOI:10.26442/18151434.2024.4.203111
28. Chapko YaS, Dubovichenko DM, Ruzhnikova AA, et al. Use of empegfilgrastim for primary prevention of febrile neutropenia in patients receiving myelosuppressive therapy. Experience of the Arkhangelsk Clinical Oncological Dispensary. Podderzhivayushchaya terapiya v onkologii = Supportive Therapy in Oncology. 2024;1(2):23-31 (in Russian). DOI:10.17650/3034-2473-2024-1-2-23-31
29. Saevets VV, Kuzmin NK, Shamanova AY, et al. Cost-effectiveness of using granulocyte colony-stimulating factor in the treatment of uterine body leiomyosarcomas. A retrospective analysis. Journal of Modern Oncology. 2024;26(3):335-40 (in Russian). DOI:10.26442/18151434.2024.3.203011
30. Nesterova ES, Mangasarova JK, Bagova MO, et al. Evaluation of the effectiveness of hematopoietic blood stem cell mobilization using empegfilgrastim (Extimia®, BIOCAD) in patients with lymphoproliferative diseases: the experience of several centers in the Russian Federation. A retrospective study. Journal of Modern Oncology. 2024;26(3):323-34 (in Russian). DOI:10.26442/18151434.2024.3.202989
31. Salgado R, Denkert C, Demaria S, et al. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol. 2015;26(2):259-71. DOI:10.1093/annonc/mdu450
32. Gianni L, Pienkowski T, Im YH, et al. 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial. Lancet Oncol. 2016;17(6):791-800. DOI:10.1016/S1470-2045(16)00163-7
33. Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13(1):25-32. DOI:10.1016/S1470-2045(11)70336-9
34. Shao Z, Pang D, Yang H, et al. Efficacy, Safety, and Tolerability of Pertuzumab, Trastuzumab, and Docetaxel for Patients With Early or Locally Advanced ERBB2-Positive Breast Cancer in Asia: The PEONY Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020;6(3):e193692. DOI:10.1001/jamaoncol.2019.3692
35. Schneeweiss A, Chia S, Hickish T, et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013;24(9):2278-84. DOI:10.1093/annonc/mdt182
36. Swain SM, Ewer MS, Viale G, et al. Pertuzumab, trastuzumab, and standard anthracycline- and taxane-based chemotherapy for the neoadjuvant treatment of patients with HER2-positive localized breast cancer (BERENICE): a phase II, open-label, multicenter, multinational cardiac safety study. Ann Oncol. 2018;29(3):646-53. DOI:10.1093/annonc/mdx773
37. Nitz UA, Gluz O, Christgen M, et al. De-escalation strategies in HER2-positive early breast cancer (EBC): final analysis of the WSG-ADAPT HER2+/HR- phase II trial: efficacy, safety, and predictive markers for 12 weeks of neoadjuvant dual blockade with trastuzumab and pertuzumab ± weekly paclitaxel. Ann Oncol. 2017;28(11):2768-72. DOI:10.1093/annonc/mdx494
38. Hurvitz SA, Martin M, Symmans WF, et al. Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2018;19(1):115-26. DOI:10.1016/S1470-2045(17)30716-7
39. Singh JC, Mamtani A, Barrio A, et al. Pathologic Complete Response with Neoadjuvant Doxorubicin and Cyclophosphamide Followed by Paclitaxel with Trastuzumab and Pertuzumab in Patients with HER2-Positive Early Stage Breast Cancer: A Single Center Experience. Oncologist. 2017;22(2):139-43. DOI:10.1634/theoncologist.2016-0268
40. Thaler S, Schmidt M, Roβwag S, et al. Proteasome inhibitors prevent bi-directional HER2/estrogen-receptor cross-talk leading to cell death in endocrine and lapatinib-resistant HER2+/ER+ breast cancer cells. Oncotarget. 2017;8(42):72281-301. DOI:10.18632/oncotarget.20261
41. Chen HL, Chen Q, Deng YC. Pathologic complete response to neoadjuvant anti-HER2 therapy is associated with HER2 immunohistochemistry score in HER2-positive early breast cancer. Medicine (Baltimore). 2021;100(44):e27632. DOI:10.1097/MD.0000000000027632
42. Gilbar P, McPherson I, Sorour N, et al. High incidence of febrile neutropenia following adjuvant breast chemotherapy with docetaxel, carboplatin and trastuzumab. Breast Cancer Manage. 2014;3(4):327-333. DOI:10.2217/bmt.14.22
43. Cavalloni G, Sarotto I, Pignochino Y, et al. Granulocyte-colony stimulating factor upregulates ErbB2 expression on breast cancer cell lines and converts primary resistance to trastuzumab. Anticancer Drugs. 2008;19(7):689-96. DOI:10.1097/CAD.0b013e3283050083
44. Gruosso T, Gigoux M, Manem VSK, et al. Spatially distinct tumor immune microenvironments stratify triple-negative breast cancers. J Clin Invest. 2019;129(4):1785-800. DOI:10.1172/JCI96313
45. Wang XQ, Danenberg E, Huang CS, et al. Spatial predictors of immunotherapy response in triple-negative breast cancer. Nature. 2023;621(7980):868-76. DOI:10.1038/s41586-023-06498-3
46. Denkert C. The immunogenicity of breast cancer--molecular subtypes matter. Ann Oncol. 2014;25(8):1453-5. DOI:10.1093/annonc/mdu235
47. Liefaard MC, van der Voort A, van Seijen M, et al. Tumor-infiltrating lymphocytes in HER2-positive breast cancer treated with neoadjuvant chemotherapy and dual HER2-blockade. NPJ Breast Cancer. 2024;10(1):29. DOI:10.1038/s41523-024-00636-4
48. Xu L, Saunders K, Huang SP, et al. A comprehensive single-cell breast tumor atlas defines epithelial and immune heterogeneity and interactions predicting anti-PD-1 therapy response. Cell Rep Med. 2024;5(5):101511. DOI:10.1016/j.xcrm.2024.10151
2. Pauletti G, Dandekar S, Rong H, et al. Assessment of methods for tissue-based detection of the HER-2/neu alteration in human breast cancer: a direct comparison of fluorescence in situ hybridization and immunohistochemistry. J Clin Oncol. 2000;18(21):3651-64. DOI:10.1200/JCO.2000.18.21.3651
3. Gradishar WJ, Moran MS, Abraham J, et al. NCCN Guidelines® Insights: Breast Cancer, Version 5.2025. J Natl Compr Canc Netw. 2025;23(11):426-36. DOI:10.6004/jnccn.2025.0053
4. Broglio KR, Quintana M, Foster M, et al. Association of Pathologic Complete Response to Neoadjuvant Therapy in HER2-Positive Breast Cancer With Long-Term Outcomes: A Meta-Analysis. JAMA Oncol. 2016;2(6):751-60. DOI:10.1001/jamaoncol.2015.6113
5. Hall BJ, Bhojwani AA, Wong H, et al. Neoadjuvant Trastuzumab and Pertuzumab for Early HER2-Positive Breast Cancer: A Real World Experience. Breast J. 2022;2022:7146172. DOI:10.1155/2022/7146172
6. Zhou M, Wang S, Wan N, et al. Efficacy and safety of neoadjuvant pertuzumab plus trastuzumab in combination with chemotherapy regimen in Chinese patients with HER2-positive early breast cancer: a real-world retrospective multi-center cohort study. Ann Transl Med. 2022;10(24):1387. DOI:10.21037/atm-22-6054
7. Conte P, Schneeweiss A, Loibl S, et al. Patient-reported outcomes from KATHERINE: A phase 3 study of adjuvant trastuzumab emtansine versus trastuzumab in patients with residual invasive disease after neoadjuvant therapy for human epidermal growth factor receptor 2-positive breast cancer. Cancer. 2020;126(13):3132-9. DOI:10.1002/cncr.32873
8. Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384(9938):164-72. DOI:10.1016/S0140-6736(13)62422-8
9. Davey MG, Browne F, Miller N, et al. Pathological complete response as a surrogate to improved survival in human epidermal growth factor receptor-2-positive breast cancer: systematic review and meta-analysis. BJS Open. 2022;6(3):zrac028.
10. Iorio MD, Elliott MJ, Scott JL, et al. Real-world outcomes of patients with human epidermal growth factor 2 (HER2)-positive breast cancer receiving neoadjuvant therapy without adjuvant ado-trastuzumab emtansine (T-DM1). J Clin Oncol. 2022;40(Suppl. 16):584. DOI:10.1200/JCO.2022.40. 16_suppl.584
11. Loibl S, André F, Bachelot T, et al. Early breast cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024;35(2):159-82. DOI:10.1016/j.annonc.2023.11.016
12. Sun HK, Jiang WL, Zhang SL, et al. Predictive value of tumor-infiltrating lymphocytes for neoadjuvant therapy response in triple-negative breast cancer: A systematic review and meta-analysis. World J Clin Oncol. 2024;15(7):920-35. DOI:10.5306/wjco.v15.i7.920
13. Finkelman BS, Zhang H, Hicks DG, et al. Tumor infiltrating lymphocytes in breast cancer: A narrative review with focus on analytic validity, clinical validity, and clinical utility. Hum Pathol. 2025;162:105866. DOI:10.1016/j.humpath.2025.105866
14. Zakaria D, Feuerhake F, Garke M, et al. Impact of tumor-infiltrating lymphocytes (TILs) on the pathological complete response (pCR) after neoadjuvant chemotherapy in triple-negative and HER2-positive breast cancer. ESMO Open. 2025
15. Denkert C, von Minckwitz G, Darb-Esfahani S, et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol. 2018;19(1):40-50. DOI:10.1016/S1470-2045(17)30904-X
16. de Jong VMT, Wang Y, Ter Hoeve ND, et al. Prognostic Value of Stromal Tumor-Infiltrating Lymphocytes in Young, Node-Negative, Triple-Negative Breast Cancer Patients Who Did Not Receive (neo)Adjuvant Systemic Therapy. J Clin Oncol. 2022;40(21):2361-74. DOI:10.1200/JCO.21.01536
17. Tsao LC, Crosby EJ, Trotter TN, et al. Trastuzumab/pertuzumab combination therapy stimulates antitumor responses through complement-dependent cytotoxicity and phagocytosis. JCI Insight. 2022;7(6):e155636. DOI:10.1172/jci.insight.155636
18. Kınıkoğlu O, Altıntaş YE, Yıldız A, et al. Tumor-infiltrating lymphocytes as predictive biomarkers in neoadjuvant treatment of HER2-positive breast cancer. Oncologist. 2025;30(4):oyaf054. DOI:10.1093/oncolo/oyaf054
19. Karagiannidis I, Salataj E, Said Abu Egal E, Beswick EJ. G-CSF in tumors: Aggressiveness, tumor microenvironment and immune cell regulation. Cytokine. 2021;142:155479. DOI:10.1016/j.cyto.2021.155479
20. Eruslanov EB, Bhojnagarwala PS, Quatromoni JG, et al. Tumor-associated neutrophils stimulate T cell responses in early-stage human lung cancer. J Clin Invest. 2014;124(12):5466-80. DOI:10.1172/JCI77053
21. Singhal S, Bhojnagarwala PS, O'Brien S, et al. Origin and Role of a Subset of Tumor-Associated Neutrophils with Antigen-Presenting Cell Features in Early-Stage Human Lung Cancer. Cancer Cell. 2016;30(1):120-35. DOI:10.1016/j.ccell.2016.06.001
22. Снеговой А.В., Кононенко И.Б., Радюкова И.М., и др. Эффективность и безопасность применения препарата эмпэгфилграстим (Экстимия®) у пациентов с солидными опухолями, получающих цитотоксическую терапию: финальные результаты исследования DEFENDOR. Современная Онкология. 2024;26(2):159-71 [Snegovoy AV, Kononenko IB, Radiukova IM, et al. Effectiveness and safety of empegfilgrastim (Extimia®) in patients with solid tumors receiving cytotoxic therapy: final results of the DEFENDOR study. Journal of Modern Oncology. 2024;26(2):159-71 (in Russian)]. DOI:10.26442/18151434.2024.2.202829
23. Zhukova L, Ibragimova T, Filonenko D, et al. DEFENDOR SPECIAL: Effect of primary prophylaxis with empegfilgrastim on pCR rate after neoadjuvant TCHP in early HER2+ breast cancer patients – Matching-adjusted indirect comparison (MAIC). J Clin Oncol. 2025;43(Suppl. 16). DOI:10.1200/JCO.2025.43.16_suppl.e13011
24. Tryakin A, Dinaeva E, Fedyanin M, et al. 1865P DEFENDOR special: Real-world use of pegylated granulocyte-colony stimulating factor in patients with gastrointestinal cancers. Annals of Oncology. 2024;35:S1096. DOI:10.1016/j.annonc.2024.08.1959
25. Нестерова Е.C., Сайдуллаева А.Ф., Шерстнев Д.Г., и др. Эффективность и безопасность применения препарата эмпэгфилграстим (Экстимия®, БИОКАД) у пациентов с лимфопролиферативными заболеваниями, получающих цитотоксическую терапию: результаты многоцентрового ретроспективно-проспективного наблюдательного пострегистрационного исследования LEGERITY. Современная Онкология. 2023;25(4):80-8 [Nesterova ES, Saydullaeva AF, Sherstnev DG, et al. Effectiveness and safety of empegfilgrastim (Extimia®, BIOCAD) in patients with lymphoproliferative diseases who receive cytotoxic therapy: results of LEGERITY, the second interim analysis of multicenter retrospective-and-prospective observational post-marketing study. Journal of Modern Oncology. 2022;24(1):80-8 (in Russian)]. DOI:10.26442/18151434.2022.1.201493
26. Спорник А.А, Васильев Н.С., Самойлова А.А., и др. Первичная профилактика нейтропении эмпэгфилграстимом у пациентов с распространенными стадиями классической лимфомы Ходжкина, получавших интенсивную химиотерапию первой линии по модифицированной программе 6 циклов EACODD-14 в рамках протокола «ЛХ-Россия-1». Клиническая онкогематология. 2023;16(4):370-9 [Spornik AA, Vasilev NS, Samoilova AA, et al. Primary prevention of neutropenia by empegfilgrastim in patients with advanced stages of classical hodgkin lymphoma treated with intensive first-line chemotherapy with a modified 6-cycle program EACODD-14 under the protocol “LKh-Rossiya-1”. Clinical Oncohematology. 2023;16(4):370-9 (in Russian)]. DOI:10.21320/2500-2139-2023-16-4-370-379
27. Кремнева Н.В., Дудина Г.А., Тагиева Э.У., и др. Применение гранулоцитарных колониестимулирующих факторов у пациентов с ВИЧ-ассоциированными лимфопролиферативными заболеваниями, получающих цитотоксическую терапию: опыт исследовательского центра. Современная Онкология. 2025;26(4):468-72 [Kremneva NV, Dudina GA, Tagieva EU, et al. Use of granulocyte colony-stimulating factors in patients with HIV-associated lymphoproliferative diseases receiving cytotoxic therapy: Experience of a research center. Journal of Modern Oncology. 2025;26(4):468-72 (in Russian)]. DOI:10.26442/18151434.2024.4.203111
28. Чапко Я.С., Дубовиченко Д.М., Ружникова А.А., и др. Применение препарата эмпэгфилграстим для первичной профилактики фебрильной нейтропении у пациентов, получающих миелосупрессивную терапию. Опыт Архангельского клинического онкологического диспансера. Поддерживающая терапия в онкологии. 2024;1(2):23-31 [Chapko YaS, Dubovichenko DM, Ruzhnikova AA, et al. Use of empegfilgrastim for primary prevention of febrile neutropenia in patients receiving myelosuppressive therapy. Experience of the Arkhangelsk Clinical Oncological Dispensary. Podderzhivayushchaya terapiya v onkologii = Supportive Therapy in Oncology. 2024;1(2):23-31 (in Russian)]. DOI:10.17650/3034-2473-2024-1-2-23-31
29. Саевец В.В., Кузьмин Н.К., Шаманова А.Ю., и др. Экономическая эффективность применения гранулоцитарного колониестимулирующего фактора при лечении лейомиосарком тела матки. Современная Онкология. 2024;26(3):335-40 [Saevets VV, Kuzmin NK, Shamanova AY, et al. Cost-effectiveness of using granulocyte colony-stimulating factor in the treatment of uterine body leiomyosarcomas. A retrospective analysis. Journal of Modern Oncology. 2024;26(3):335-40 (in Russian)]. DOI:10.26442/18151434.2024.3.203011
30. Нестерова Е.С., Мангасарова Я.К., Багова М.О., и др. Оценка эффективности мобилизации гемопоэтических стволовых клеток крови с применением препарата эмпэгфилграстим (Экстимия®, АО «Биокад») у больных лимфопролиферативными заболеваниями: опыт нескольких центров на территории Российской Федерации. Современная Онкология. 2024;26(3):323-34 [Nesterova ES, Mangasarova JK, Bagova MO, et al. Evaluation of the effectiveness of hematopoietic blood stem cell mobilization using empegfilgrastim (Extimia®, BIOCAD) in patients with lymphoproliferative diseases: the experience of several centers in the Russian Federation. A retrospective study. Journal of Modern Oncology. 2024;26(3):323-34 (in Russian)]. DOI:10.26442/18151434.2024.3.202989
31. Salgado R, Denkert C, Demaria S, et al. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol. 2015;26(2):259-71. DOI:10.1093/annonc/mdu450
32. Gianni L, Pienkowski T, Im YH, et al. 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial. Lancet Oncol. 2016;17(6):791-800. DOI:10.1016/S1470-2045(16)00163-7
33. Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13(1):25-32. DOI:10.1016/S1470-2045(11)70336-9
34. Shao Z, Pang D, Yang H, et al. Efficacy, Safety, and Tolerability of Pertuzumab, Trastuzumab, and Docetaxel for Patients With Early or Locally Advanced ERBB2-Positive Breast Cancer in Asia: The PEONY Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020;6(3):e193692. DOI:10.1001/jamaoncol.2019.3692
35. Schneeweiss A, Chia S, Hickish T, et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013;24(9):2278-84. DOI:10.1093/annonc/mdt182
36. Swain SM, Ewer MS, Viale G, et al. Pertuzumab, trastuzumab, and standard anthracycline- and taxane-based chemotherapy for the neoadjuvant treatment of patients with HER2-positive localized breast cancer (BERENICE): a phase II, open-label, multicenter, multinational cardiac safety study. Ann Oncol. 2018;29(3):646-53. DOI:10.1093/annonc/mdx773
37. Nitz UA, Gluz O, Christgen M, et al. De-escalation strategies in HER2-positive early breast cancer (EBC): final analysis of the WSG-ADAPT HER2+/HR- phase II trial: efficacy, safety, and predictive markers for 12 weeks of neoadjuvant dual blockade with trastuzumab and pertuzumab ± weekly paclitaxel. Ann Oncol. 2017;28(11):2768-72. DOI:10.1093/annonc/mdx494
38. Hurvitz SA, Martin M, Symmans WF, et al. Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2018;19(1):115-26. DOI:10.1016/S1470-2045(17)30716-7
39. Singh JC, Mamtani A, Barrio A, et al. Pathologic Complete Response with Neoadjuvant Doxorubicin and Cyclophosphamide Followed by Paclitaxel with Trastuzumab and Pertuzumab in Patients with HER2-Positive Early Stage Breast Cancer: A Single Center Experience. Oncologist. 2017;22(2):139-43. DOI:10.1634/theoncologist.2016-0268
40. Thaler S, Schmidt M, Roβwag S, et al. Proteasome inhibitors prevent bi-directional HER2/estrogen-receptor cross-talk leading to cell death in endocrine and lapatinib-resistant HER2+/ER+ breast cancer cells. Oncotarget. 2017;8(42):72281-301. DOI:10.18632/oncotarget.20261
41. Chen HL, Chen Q, Deng YC. Pathologic complete response to neoadjuvant anti-HER2 therapy is associated with HER2 immunohistochemistry score in HER2-positive early breast cancer. Medicine (Baltimore). 2021;100(44):e27632. DOI:10.1097/MD.0000000000027632
42. Gilbar P, McPherson I, Sorour N, et al. High incidence of febrile neutropenia following adjuvant breast chemotherapy with docetaxel, carboplatin and trastuzumab. Breast Cancer Manage. 2014;3(4):327-333. DOI:10.2217/bmt.14.22
43. Cavalloni G, Sarotto I, Pignochino Y, et al. Granulocyte-colony stimulating factor upregulates ErbB2 expression on breast cancer cell lines and converts primary resistance to trastuzumab. Anticancer Drugs. 2008;19(7):689-96. DOI:10.1097/CAD.0b013e3283050083
44. Gruosso T, Gigoux M, Manem VSK, et al. Spatially distinct tumor immune microenvironments stratify triple-negative breast cancers. J Clin Invest. 2019;129(4):1785-800. DOI:10.1172/JCI96313
45. Wang XQ, Danenberg E, Huang CS, et al. Spatial predictors of immunotherapy response in triple-negative breast cancer. Nature. 2023;621(7980):868-76. DOI:10.1038/s41586-023-06498-3
46. Denkert C. The immunogenicity of breast cancer--molecular subtypes matter. Ann Oncol. 2014;25(8):1453-5. DOI:10.1093/annonc/mdu235
47. Liefaard MC, van der Voort A, van Seijen M, et al. Tumor-infiltrating lymphocytes in HER2-positive breast cancer treated with neoadjuvant chemotherapy and dual HER2-blockade. NPJ Breast Cancer. 2024;10(1):29. DOI:10.1038/s41523-024-00636-4
48. Xu L, Saunders K, Huang SP, et al. A comprehensive single-cell breast tumor atlas defines epithelial and immune heterogeneity and interactions predicting anti-PD-1 therapy response. Cell Rep Med. 2024;5(5):101511. DOI:10.1016/j.xcrm.2024.10151
________________________________________________
2. Pauletti G, Dandekar S, Rong H, et al. Assessment of methods for tissue-based detection of the HER-2/neu alteration in human breast cancer: a direct comparison of fluorescence in situ hybridization and immunohistochemistry. J Clin Oncol. 2000;18(21):3651-64. DOI:10.1200/JCO.2000.18.21.3651
3. Gradishar WJ, Moran MS, Abraham J, et al. NCCN Guidelines® Insights: Breast Cancer, Version 5.2025. J Natl Compr Canc Netw. 2025;23(11):426-36. DOI:10.6004/jnccn.2025.0053
4. Broglio KR, Quintana M, Foster M, et al. Association of Pathologic Complete Response to Neoadjuvant Therapy in HER2-Positive Breast Cancer With Long-Term Outcomes: A Meta-Analysis. JAMA Oncol. 2016;2(6):751-60. DOI:10.1001/jamaoncol.2015.6113
5. Hall BJ, Bhojwani AA, Wong H, et al. Neoadjuvant Trastuzumab and Pertuzumab for Early HER2-Positive Breast Cancer: A Real World Experience. Breast J. 2022;2022:7146172. DOI:10.1155/2022/7146172
6. Zhou M, Wang S, Wan N, et al. Efficacy and safety of neoadjuvant pertuzumab plus trastuzumab in combination with chemotherapy regimen in Chinese patients with HER2-positive early breast cancer: a real-world retrospective multi-center cohort study. Ann Transl Med. 2022;10(24):1387. DOI:10.21037/atm-22-6054
7. Conte P, Schneeweiss A, Loibl S, et al. Patient-reported outcomes from KATHERINE: A phase 3 study of adjuvant trastuzumab emtansine versus trastuzumab in patients with residual invasive disease after neoadjuvant therapy for human epidermal growth factor receptor 2-positive breast cancer. Cancer. 2020;126(13):3132-9. DOI:10.1002/cncr.32873
8. Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384(9938):164-72. DOI:10.1016/S0140-6736(13)62422-8
9. Davey MG, Browne F, Miller N, et al. Pathological complete response as a surrogate to improved survival in human epidermal growth factor receptor-2-positive breast cancer: systematic review and meta-analysis. BJS Open. 2022;6(3):zrac028.
10. Iorio MD, Elliott MJ, Scott JL, et al. Real-world outcomes of patients with human epidermal growth factor 2 (HER2)-positive breast cancer receiving neoadjuvant therapy without adjuvant ado-trastuzumab emtansine (T-DM1). J Clin Oncol. 2022;40(Suppl. 16):584. DOI:10.1200/JCO.2022.40. 16_suppl.584
11. Loibl S, André F, Bachelot T, et al. Early breast cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024;35(2):159-82. DOI:10.1016/j.annonc.2023.11.016
12. Sun HK, Jiang WL, Zhang SL, et al. Predictive value of tumor-infiltrating lymphocytes for neoadjuvant therapy response in triple-negative breast cancer: A systematic review and meta-analysis. World J Clin Oncol. 2024;15(7):920-35. DOI:10.5306/wjco.v15.i7.920
13. Finkelman BS, Zhang H, Hicks DG, et al. Tumor infiltrating lymphocytes in breast cancer: A narrative review with focus on analytic validity, clinical validity, and clinical utility. Hum Pathol. 2025;162:105866. DOI:10.1016/j.humpath.2025.105866
14. Zakaria D, Feuerhake F, Garke M, et al. Impact of tumor-infiltrating lymphocytes (TILs) on the pathological complete response (pCR) after neoadjuvant chemotherapy in triple-negative and HER2-positive breast cancer. ESMO Open. 2025
15. Denkert C, von Minckwitz G, Darb-Esfahani S, et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol. 2018;19(1):40-50. DOI:10.1016/S1470-2045(17)30904-X
16. de Jong VMT, Wang Y, Ter Hoeve ND, et al. Prognostic Value of Stromal Tumor-Infiltrating Lymphocytes in Young, Node-Negative, Triple-Negative Breast Cancer Patients Who Did Not Receive (neo)Adjuvant Systemic Therapy. J Clin Oncol. 2022;40(21):2361-74. DOI:10.1200/JCO.21.01536
17. Tsao LC, Crosby EJ, Trotter TN, et al. Trastuzumab/pertuzumab combination therapy stimulates antitumor responses through complement-dependent cytotoxicity and phagocytosis. JCI Insight. 2022;7(6):e155636. DOI:10.1172/jci.insight.155636
18. Kınıkoğlu O, Altıntaş YE, Yıldız A, et al. Tumor-infiltrating lymphocytes as predictive biomarkers in neoadjuvant treatment of HER2-positive breast cancer. Oncologist. 2025;30(4):oyaf054. DOI:10.1093/oncolo/oyaf054
19. Karagiannidis I, Salataj E, Said Abu Egal E, Beswick EJ. G-CSF in tumors: Aggressiveness, tumor microenvironment and immune cell regulation. Cytokine. 2021;142:155479. DOI:10.1016/j.cyto.2021.155479
20. Eruslanov EB, Bhojnagarwala PS, Quatromoni JG, et al. Tumor-associated neutrophils stimulate T cell responses in early-stage human lung cancer. J Clin Invest. 2014;124(12):5466-80. DOI:10.1172/JCI77053
21. Singhal S, Bhojnagarwala PS, O'Brien S, et al. Origin and Role of a Subset of Tumor-Associated Neutrophils with Antigen-Presenting Cell Features in Early-Stage Human Lung Cancer. Cancer Cell. 2016;30(1):120-35. DOI:10.1016/j.ccell.2016.06.001
22. Snegovoy AV, Kononenko IB, Radiukova IM, et al. Effectiveness and safety of empegfilgrastim (Extimia®) in patients with solid tumors receiving cytotoxic therapy: final results of the DEFENDOR study. Journal of Modern Oncology. 2024;26(2):159-71 (in Russian). DOI:10.26442/18151434.2024.2.202829
23. Zhukova L, Ibragimova T, Filonenko D, et al. DEFENDOR SPECIAL: Effect of primary prophylaxis with empegfilgrastim on pCR rate after neoadjuvant TCHP in early HER2+ breast cancer patients – Matching-adjusted indirect comparison (MAIC). J Clin Oncol. 2025;43(Suppl. 16). DOI:10.1200/JCO.2025.43.16_suppl.e13011
24. Tryakin A, Dinaeva E, Fedyanin M, et al. 1865P DEFENDOR special: Real-world use of pegylated granulocyte-colony stimulating factor in patients with gastrointestinal cancers. Annals of Oncology. 2024;35:S1096. DOI:10.1016/j.annonc.2024.08.1959
25. Nesterova ES, Saydullaeva AF, Sherstnev DG, et al. Effectiveness and safety of empegfilgrastim (Extimia®, BIOCAD) in patients with lymphoproliferative diseases who receive cytotoxic therapy: results of LEGERITY, the second interim analysis of multicenter retrospective-and-prospective observational post-marketing study. Journal of Modern Oncology. 2022;24(1):80-8 (in Russian). DOI:10.26442/18151434.2022.1.201493
26. Spornik AA, Vasilev NS, Samoilova AA, et al. Primary prevention of neutropenia by empegfilgrastim in patients with advanced stages of classical hodgkin lymphoma treated with intensive first-line chemotherapy with a modified 6-cycle program EACODD-14 under the protocol “LKh-Rossiya-1”. Clinical Oncohematology. 2023;16(4):370-9 (in Russian). DOI:10.21320/2500-2139-2023-16-4-370-379
27. Kremneva NV, Dudina GA, Tagieva EU, et al. Use of granulocyte colony-stimulating factors in patients with HIV-associated lymphoproliferative diseases receiving cytotoxic therapy: Experience of a research center. Journal of Modern Oncology. 2025;26(4):468-72 (in Russian). DOI:10.26442/18151434.2024.4.203111
28. Chapko YaS, Dubovichenko DM, Ruzhnikova AA, et al. Use of empegfilgrastim for primary prevention of febrile neutropenia in patients receiving myelosuppressive therapy. Experience of the Arkhangelsk Clinical Oncological Dispensary. Podderzhivayushchaya terapiya v onkologii = Supportive Therapy in Oncology. 2024;1(2):23-31 (in Russian). DOI:10.17650/3034-2473-2024-1-2-23-31
29. Saevets VV, Kuzmin NK, Shamanova AY, et al. Cost-effectiveness of using granulocyte colony-stimulating factor in the treatment of uterine body leiomyosarcomas. A retrospective analysis. Journal of Modern Oncology. 2024;26(3):335-40 (in Russian). DOI:10.26442/18151434.2024.3.203011
30. Nesterova ES, Mangasarova JK, Bagova MO, et al. Evaluation of the effectiveness of hematopoietic blood stem cell mobilization using empegfilgrastim (Extimia®, BIOCAD) in patients with lymphoproliferative diseases: the experience of several centers in the Russian Federation. A retrospective study. Journal of Modern Oncology. 2024;26(3):323-34 (in Russian). DOI:10.26442/18151434.2024.3.202989
31. Salgado R, Denkert C, Demaria S, et al. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol. 2015;26(2):259-71. DOI:10.1093/annonc/mdu450
32. Gianni L, Pienkowski T, Im YH, et al. 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial. Lancet Oncol. 2016;17(6):791-800. DOI:10.1016/S1470-2045(16)00163-7
33. Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13(1):25-32. DOI:10.1016/S1470-2045(11)70336-9
34. Shao Z, Pang D, Yang H, et al. Efficacy, Safety, and Tolerability of Pertuzumab, Trastuzumab, and Docetaxel for Patients With Early or Locally Advanced ERBB2-Positive Breast Cancer in Asia: The PEONY Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020;6(3):e193692. DOI:10.1001/jamaoncol.2019.3692
35. Schneeweiss A, Chia S, Hickish T, et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013;24(9):2278-84. DOI:10.1093/annonc/mdt182
36. Swain SM, Ewer MS, Viale G, et al. Pertuzumab, trastuzumab, and standard anthracycline- and taxane-based chemotherapy for the neoadjuvant treatment of patients with HER2-positive localized breast cancer (BERENICE): a phase II, open-label, multicenter, multinational cardiac safety study. Ann Oncol. 2018;29(3):646-53. DOI:10.1093/annonc/mdx773
37. Nitz UA, Gluz O, Christgen M, et al. De-escalation strategies in HER2-positive early breast cancer (EBC): final analysis of the WSG-ADAPT HER2+/HR- phase II trial: efficacy, safety, and predictive markers for 12 weeks of neoadjuvant dual blockade with trastuzumab and pertuzumab ± weekly paclitaxel. Ann Oncol. 2017;28(11):2768-72. DOI:10.1093/annonc/mdx494
38. Hurvitz SA, Martin M, Symmans WF, et al. Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2018;19(1):115-26. DOI:10.1016/S1470-2045(17)30716-7
39. Singh JC, Mamtani A, Barrio A, et al. Pathologic Complete Response with Neoadjuvant Doxorubicin and Cyclophosphamide Followed by Paclitaxel with Trastuzumab and Pertuzumab in Patients with HER2-Positive Early Stage Breast Cancer: A Single Center Experience. Oncologist. 2017;22(2):139-43. DOI:10.1634/theoncologist.2016-0268
40. Thaler S, Schmidt M, Roβwag S, et al. Proteasome inhibitors prevent bi-directional HER2/estrogen-receptor cross-talk leading to cell death in endocrine and lapatinib-resistant HER2+/ER+ breast cancer cells. Oncotarget. 2017;8(42):72281-301. DOI:10.18632/oncotarget.20261
41. Chen HL, Chen Q, Deng YC. Pathologic complete response to neoadjuvant anti-HER2 therapy is associated with HER2 immunohistochemistry score in HER2-positive early breast cancer. Medicine (Baltimore). 2021;100(44):e27632. DOI:10.1097/MD.0000000000027632
42. Gilbar P, McPherson I, Sorour N, et al. High incidence of febrile neutropenia following adjuvant breast chemotherapy with docetaxel, carboplatin and trastuzumab. Breast Cancer Manage. 2014;3(4):327-333. DOI:10.2217/bmt.14.22
43. Cavalloni G, Sarotto I, Pignochino Y, et al. Granulocyte-colony stimulating factor upregulates ErbB2 expression on breast cancer cell lines and converts primary resistance to trastuzumab. Anticancer Drugs. 2008;19(7):689-96. DOI:10.1097/CAD.0b013e3283050083
44. Gruosso T, Gigoux M, Manem VSK, et al. Spatially distinct tumor immune microenvironments stratify triple-negative breast cancers. J Clin Invest. 2019;129(4):1785-800. DOI:10.1172/JCI96313
45. Wang XQ, Danenberg E, Huang CS, et al. Spatial predictors of immunotherapy response in triple-negative breast cancer. Nature. 2023;621(7980):868-76. DOI:10.1038/s41586-023-06498-3
46. Denkert C. The immunogenicity of breast cancer--molecular subtypes matter. Ann Oncol. 2014;25(8):1453-5. DOI:10.1093/annonc/mdu235
47. Liefaard MC, van der Voort A, van Seijen M, et al. Tumor-infiltrating lymphocytes in HER2-positive breast cancer treated with neoadjuvant chemotherapy and dual HER2-blockade. NPJ Breast Cancer. 2024;10(1):29. DOI:10.1038/s41523-024-00636-4
48. Xu L, Saunders K, Huang SP, et al. A comprehensive single-cell breast tumor atlas defines epithelial and immune heterogeneity and interactions predicting anti-PD-1 therapy response. Cell Rep Med. 2024;5(5):101511. DOI:10.1016/j.xcrm.2024.10151
Авторы
Л.Г. Жукова*1, Т.М. Ибрагимова1, Д.А. Филоненко1, И.П. Ганьшина2, И.В. Сорокина1, А.А. Лазарев3, О.Н. Мироненко4, О.Н. Просяникова5
1ГБУЗ «Московский клинический научно-практический центр им. А.С. Логинова» Департамента здравоохранения г. Москвы, Москва, Российская Федерация
2ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России, Москва, Российская Федерация
3ФГБОУ ВО «Санкт-Петербургский государственный университет телекоммуникаций им. проф. М.А. Бонч-Бруевича», Санкт-Петербург, Российская Федерация
4ФГБОУ ВО «Российская академия народного хозяйства и государственной службы при Президенте Российской Федерации», Москва, Российская Федерация
5ФГБОУ ВО «Северо-Западный государственный медицинский университет им. И.И. Мечникова» Минздрава России, Санкт-Петербург, Российская Федерация
*zhukova.lyudmila008@gmail.com
1Loginov Moscow Clinical Scientific Center, Moscow, Russian Federation
2Blokhin National Medical Research Center of Oncology, Moscow, Russian Federation
3Bonch-Bruevich Saint Petersburg State University of Telecommunications, Saint Petersburg, Russian Federation
4Russian Presidential Academy of National Economy and Public Administration, Moscow, Russian Federation
5Mechnikov North-Western State Medical University, Saint Petersburg, Russian Federation
*zhukova.lyudmila008@gmail.com
1ГБУЗ «Московский клинический научно-практический центр им. А.С. Логинова» Департамента здравоохранения г. Москвы, Москва, Российская Федерация
2ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России, Москва, Российская Федерация
3ФГБОУ ВО «Санкт-Петербургский государственный университет телекоммуникаций им. проф. М.А. Бонч-Бруевича», Санкт-Петербург, Российская Федерация
4ФГБОУ ВО «Российская академия народного хозяйства и государственной службы при Президенте Российской Федерации», Москва, Российская Федерация
5ФГБОУ ВО «Северо-Западный государственный медицинский университет им. И.И. Мечникова» Минздрава России, Санкт-Петербург, Российская Федерация
*zhukova.lyudmila008@gmail.com
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1Loginov Moscow Clinical Scientific Center, Moscow, Russian Federation
2Blokhin National Medical Research Center of Oncology, Moscow, Russian Federation
3Bonch-Bruevich Saint Petersburg State University of Telecommunications, Saint Petersburg, Russian Federation
4Russian Presidential Academy of National Economy and Public Administration, Moscow, Russian Federation
5Mechnikov North-Western State Medical University, Saint Petersburg, Russian Federation
*zhukova.lyudmila008@gmail.com
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