Evolution of anti-HER2 therapy in advanced HER2+ breast cancer or “why is trastuzumab still a key player?”. A review

Cover Page

Cite item

Full Text

Abstract

The use of anti-HER2 therapy has dramatically changed the prognosis of patients with HER2+ breast cancer both in the early and advanced stages. New options that demonstrate the effectiveness of treatment of patients with HER2+ breast cancer can significantly increase the median progression-free survival and the overall frequency of objective response, the duration of this response. Some of them are still approved only in the first-line treatment of the metastatic form, either neo- or adjuvant regimens (for example, pertuzumab). At the same time, the antitumor conjugates being created, such as T-DM1 or T-DxD, have a common link in their structure – the monoclonal base antibody trastuzumab. Despite all the success of this class of drugs, progression occurs at a certain stage in these patients, and it is trastuzumab in combination with various chemotherapeutic regimens and/or drugs of other classes that remains the standard of late-line therapy and ensures the prolongation of patients' lives.

About the authors

Katerina S. Grechukhina

Loginov Moscow Clinical Scientific Center

Author for correspondence.
Email: dr.grechukhina@gmail.com
ORCID iD: 0000-0002-0616-5477

Cand. Sci. (Med.)

Russian Federation, Moscow

Margarita V. Sukhova

Loginov Moscow Clinical Scientific Center

Email: dr.grechukhina@gmail.com
ORCID iD: 0009-0004-7119-0160

oncologist

Russian Federation, Moscow

Elena M. Kolyago

Loginov Moscow Clinical Scientific Center

Email: dr.grechukhina@gmail.com
ORCID iD: 0009-0008-3295-8236

Department Head

Russian Federation, Moscow

Daria A. Filonenko

Loginov Moscow Clinical Scientific Center

Email: dr.grechukhina@gmail.com
ORCID iD: 0000-0002-7224-3111

Cand. Sci. (Med.)

Russian Federation, Moscow

Liudmila G. Zhukova

Loginov Moscow Clinical Scientific Center

Email: dr.grechukhina@gmail.com
ORCID iD: 0000-0003-4848-6938

D. Sci. (Med.), Corr. Memb. RAS

Russian Federation, Moscow

References

  1. Bedard PL, Hyman DM, Davids MS, Siu LL. Small molecules, big impact: 20 years of targeted therapy in oncology. Lancet. 2020;395(10229):1078-88. doi: 10.1016/S0140-6736(20)30164-1
  2. Cho HS, Mason K, Ramyar KX, et al. Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab. Nature. 2003;421(6924):756-60. doi: 10.1038/nature01392
  3. Rubin I, Yarden Y. The basic biology of HER2. Ann Oncol. 2001;12(Suppl. 1):S3-8. doi: 10.1093/annonc/12.suppl_1.s3
  4. Najjar MK, Manore SG, Regua AT, Lo HW. Antibody-Drug Conjugates for the Treatment of HER2-Positive Breast Cancer. Genes (Basel). 2022;13(11). doi: 10.3390/genes13112065
  5. Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2001;2(2):127-37. doi: 10.1038/35052073
  6. Van Cutsem E, Bang YJ, Feng-Yi F, et al. HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer. Gastric Cancer. 2015;18(3):476-84. doi: 10.1007/s10120-014-0402-y
  7. Vu T, Claret FX. Trastuzumab: updated mechanisms of action and resistance in breast cancer. Front Oncol. 2012;2:62. doi: 10.3389/fonc.2012.00062
  8. Ravdin P. The use of HER2 testing in the management of breast cancer. Semin Oncol. 2000;27(5 Suppl. 9):33-42.
  9. Capelan M, Pugliano L, De Azambuja E, et al. Pertuzumab: new hope for patients with HER2-positive breast cancer. Ann Oncol. 2013;24(2):273-82. doi: 10.1093/annonc/mds328
  10. Shi Y, Fan X, Deng H, et al. Trastuzumab triggers phagocytic killing of high HER2 cancer cells in vitro and in vivo by interaction with Fcγ receptors on macrophages. J Immunol. 2015;194(9):4379-86. doi: 10.4049/jimmunol.1402891
  11. Junttila TT, Akita RW, Parsons K, et al. Ligand-independent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941. Cancer Cell. 2009;15(5):429-40. doi: 10.1016/j.ccr.2009.03.020
  12. Park S, Jiang Z, Mortenson ED, et al. The therapeutic effect of anti-HER2/neu antibody depends on both innate and adaptive immunity. Cancer Cell. 2010;18(2):160-70. doi: 10.1016/j.ccr.2010.06.014
  13. Perez EA, Romond EH, Suman VJ, et al. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol. 2014;32(33):3744-52. doi: 10.1200/JCO.2014.55.5730
  14. Cameron D, Piccart-Gebhart MJ, Gelber RD, et al. 11 years' follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet. 2017;389(10075):1195-205. doi: 10.1016/S0140-6736(16)32616-2
  15. Slamon D, Eiermann W, Robert N, et al. Abstract S5-04: Ten year follow-up of BCIRG-006 comparing doxorubicin plus cyclophosphamide followed by docetaxel (AC→T) with doxorubicin plus cyclophosphamide followed by docetaxel and trastuzumab (AC→TH) with docetaxel, carboplatin and trastuzumab (TCH) in HER2+ early breast cancer. Cancer Res. 2016;76(Suppl.4):S5-04. doi: 10.1158/1538-7445.SABCS15-S5-04
  16. Колядина И.В., Поддубная И.В. Ключевые исследования, изменившие историю и принципы лечения раннего HER2+ рака молочной железы: фокус на индивидуализацию терапии. Опухоли женской репродуктивной системы. 2020;16(3):46-56 [Kolyadina IV, Poddubnaya IV. Key studies that have changed the history and treatment of early HER2+ breast cancer: focus on individual therapy. Tumors of Female Reproductive System. 2020;16(3):46-56 (in Russian)]. doi: 10.17650/1994-4098-2020-16-3-46-55
  17. Smith I, Procter M, Gelber RD, et al. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet. 2007;369(9555):29-36. doi: 10.1016/S0140-6736(07)60028-2
  18. Slamon D, Eiermann W, Robert N, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011;365(14):1273-83. doi: 10.1056/NEJMoa0910383
  19. Baselga J, Tripathy D, Mendelsohn J, et al. Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer. J Clin Oncol. 1996;14(3):737-44. doi: 10.1200/JCO.1996.14.3.737
  20. Balduzzi S, Mantarro S, Guarneri V, et al. Trastuzumab-containing regimens for metastatic breast cancer. Cochrane Database Syst Rev. 2014;2014(6):CD006242. doi: 10.1002/14651858.CD006242.pub2
  21. Marty M, Cognetti F, Maraninchi D, et al. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol. 2005;23(19):4265-74. doi: 10.1200/JCO.2005.04.173
  22. Swain SM, Baselga J, Kim SB, et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015;372(8):724-34. doi: 10.1056/NEJMoa1413513
  23. Baselga J, Cortés J, Kim SB, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012;366(2):109-19. doi: 10.1056/NEJMoa1113216
  24. Swain SM, Miles D, Kim SB, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21(4):519-30. doi: 10.1016/S1470-2045(19)30863-0
  25. Rimawi M, Ferrero JM, de la Haba-Rodriguez J, et al. First-Line Trastuzumab Plus an Aromatase Inhibitor, With or Without Pertuzumab, in Human Epidermal Growth Factor Receptor 2-Positive and Hormone Receptor-Positive Metastatic or Locally Advanced Breast Cancer (PERTAIN): A Randomized, Open-Label Phase II Trial. J Clin Oncol. 2018;36(28):2826-35. doi: 10.1200/JCO.2017.76.7863
  26. Saura C, Oliveira M, Feng YH, et al. Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA Trial. J Clin Oncol. 2020;38(27):3138-49. doi: 10.1200/JCO.20.00147
  27. Awada A, Colomer R, Inoue K, et al. Neratinib Plus Paclitaxel vs Trastuzumab Plus Paclitaxel in Previously Untreated Metastatic ERBB2-Positive Breast Cancer: The NEfERT-T Randomized Clinical Trial. JAMA Oncol. 2016;2(12):1557-64. doi: 10.1001/jamaoncol.2016.0237
  28. Murthy RK, Loi S, Okines A, et al. Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. N Engl J Med. 2020;382(7):597-609. doi: 10.1056/NEJMoa1914609
  29. Junttila TT, Li G, Parsons K, et al. Trastuzumab-DM1 (T-DM1) retains all the mechanisms of action of trastuzumab and efficiently inhibits growth of lapatinib insensitive breast cancer. Breast Cancer Res Treat. 2011;128(2):347-56. doi: 10.1007/s10549-010-1090-x
  30. Nader-Marta G, Molinelli C, Debien V, et al. Antibody-drug conjugates: the evolving field of targeted chemotherapy for breast cancer treatment. Ther Adv Med Oncol. 2023;15:17588359231183679. doi: 10.1177/17588359231183679
  31. Escrivá-de-Romaní S, Saura C. The change of paradigm in the treatment of HER2-positive breast cancer with the development of new generation antibody-drug conjugates. Cancer Drug Resist. 2023;6(1):45-58. doi: 10.20517/cdr.2022.52
  32. Verma S, Miles D, Gianni L, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012;367(19):1783-91. doi: 10.1056/NEJMoa1209124
  33. Diéras V, Miles D, Verma S, et al. Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18(6):732-42. doi: 10.1016/S1470-2045(17)30312-1
  34. Conte B, Fabi A, Poggio F, et al. T-DM1 Efficacy in Patients With HER2-positive Metastatic Breast Cancer Progressing After a Taxane Plus Pertuzumab and Trastuzumab: An Italian Multicenter Observational Study. Clin Breast Cancer. 2020;20(2):e181-7. doi: 10.1016/j.clbc.2019.09.001
  35. Doi T, Shitara K, Naito Y, et al. Safety, pharmacokinetics, and antitumour activity of trastuzumab deruxtecan (DS-8201), a HER2-targeting antibody-drug conjugate, in patients with advanced breast and gastric or gastro-oesophageal tumours: a phase 1 dose-escalation study. Lancet Oncol. 2017;18(11):1512-22. doi: 10.1016/S1470-2045(17)30604-6
  36. Modi S, Saura C, Yamashita T, et al. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. N Engl J Med. 2020;382(7):610-21. doi: 10.1056/NEJMoa1914510
  37. Hurvitz SA, Hegg R, Chung WP, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial. Lancet. 2023;401(10371):105-17. doi: 10.1016/S0140-6736(22)02420-5
  38. Xia X, Gong C, Zhang Y, Xiong H. The History and Development of HER2 Inhibitors. Pharmaceuticals (Basel). 2023;16(10). doi: 10.3390/ph16101450
  39. Hamberg P, Bos MM, Braun HJ, et al. Randomized phase II study comparing efficacy and safety of combination-therapy trastuzumab and docetaxel vs. sequential therapy of trastuzumab followed by docetaxel alone at progression as first-line chemotherapy in patients with HER2+ metastatic breast cancer: HERTAX trial. Clin Breast Cancer. 2011;11(2):103-13. doi: 10.1016/j.clbc.2011.03.003
  40. von Minckwitz G, du Bois A, Schmidt M, et al. Trastuzumab beyond progression in human epidermal growth factor receptor 2-positive advanced breast cancer: a german breast group 26/breast international group 03-05 study. J Clin Oncol. 2009;27(12):1999-2006. doi: 10.1200/JCO.2008.19.6618
  41. Essadi I, Benbrahim Z, Kaakoua M, et al. HER2-Positive Metastatic Breast Cancer: Available Treatments and Current Developments. Cancers (Basel). 2023;15(6). doi: 10.3390/cancers15061738
  42. Jackisch C, Welslau M, Schoenegg W, et al. Impact of trastuzumab treatment beyond disease progression for advanced/metastatic breast cancer on survival – results from a prospective, observational study in Germany. Breast. 2014;23(5):603-8. doi: 10.1016/j.breast.2014.06.003
  43. Breast Cancer – Guidelines NCCN 2024. Available at: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1419. Accessed: 17.04.2024.
  44. Тюляндин С.А., Артамонова Е.В., Жигулев А.Н., и др. Практические рекомендации по лечению рака молочной железы. Практические рекомендации RUSSCO, часть 1. Злокачественные опухоли. 2023;13:157-200 [Tiuliandin SA, Artamonova EV, Zhigulev AN, et al. Prakticheskie rekomendatsii po lecheniiu raka molochnoi zhelezy. Prakticheskie rekomendatsii RUSSCO, chast' 1. Zlokachestvennye opukholi. 2023;13:157-200 (in Russian)]. doi: 10.18027/2224-5057-2023-13-3S2-1-157-200
  45. Gennari A, André F, Barrios CH, et al. ESMO Clinical Practice Guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer. Ann Oncol. 2021;32(12):1475-95. doi: 10.1016/j.annonc.2021.09.019
  46. Bartsch R, Wenzel C, Altorjai G, et al. Capecitabine and trastuzumab in heavily pretreated metastatic breast cancer. J Clin Oncol. 2007;25(25):3853-8. doi: 10.1200/JCO.2007.11.9776
  47. Fabi A, Metro G, Ferretti G, et al. Do HER-2 positive metastatic breast cancer patients benefit from the use of trastuzumab beyond disease progression? A mono-institutional experience and systematic review of observational studies. Breast. 2008;17(5):499-505. doi: 10.1016/j.breast.2008.03.006
  48. O'Shaughnessy JA, Vukelja S, Marsland T, et al. Phase II study of trastuzumab plus gemcitabine in chemotherapy-pretreated patients with metastatic breast cancer. Clin Breast Cancer. 2004;5(2):142-7. doi: 10.3816/cbc.2004.n.019
  49. Osako T, Ito Y, Takahashi S, et al. Efficacy and safety of trastuzumab plus capecitabine in heavily pretreated patients with HER2-positive metastatic breast cancer. Cancer Chemother Pharmacol. 2008;62(1):159-64. doi: 10.1007/s00280-007-0586-5
  50. Lee YR, Huh SJ, Lee DH, et al. Phase II Study of Vinorelbine Plus Trastuzumab in HER2 Overexpressing Metastatic Breast Cancer Pretreated with Anthracyclines and Taxanes. J Breast Cancer. 2011;14(2):140-6. doi: 10.4048/jbc.2011.14.2.140
  51. Bartsch R, Wenzel C, Gampenrieder SP, et al. Trastuzumab and gemcitabine as salvage therapy in heavily pre-treated patients with metastatic breast cancer. Cancer Chemother Pharmacol. 2008;62(5):903-10. doi: 10.1007/s00280-008-0682-1
  52. Di Lauro V, Torrisi E, Bidoli E, et al. Trastuzumab and Gemcitabine in Pretreated HER2 Overexpressing Metastatic Breast Cancer Patients: Retrospective Analysis of Our Series. J Oncol. 2012;2012:198412. doi: 10.1155/2012/198412
  53. John M, Hinke A, Stauch M, et al. Weekly paclitaxel plus trastuzumab in metastatic breast cancer pretreated with anthracyclines--a phase II multipractice study. BMC Cancer. 2012;12:165. doi: 10.1186/1471-2407-12-165
  54. Li Y, Gong C, Lu Q, et al. Real-World Data of Triplet Combination of Trastuzumab, Lapatinib, and Chemotherapy in HER2-Positive Metastatic Breast Cancer: A Multicenter Retrospective Study. Front Oncol. 2020;10:271. doi: 10.3389/fonc.2020.00271
  55. Lutrino ES, Orlando L, Febbraro A, et al. Eribulin plus trastuzumab in pretreated HER2-positive advanced breast cancer patients: safety and efficacy. An Italian experience. Tumori. 2020;106(4):301-5. doi: 10.1177/0300891619887225
  56. Uncu D, Bayoglu IV, Arslan UY, et al. Trastuzumab-based Retreatment after Lapatinib in Heavily Pretreated HER2 Positive Metastatic Breast Cancer: an Anatolian Society of Medical Oncology Study. Asian Pac J Cancer Prev. 2015;16(9):4127-31. doi: 10.7314/apjcp.2015.16.9.4127
  57. Colomer R, Hall P, Szkultecka-Debek M, et al. Real-world treatment in patients with HER2+ metastatic breast cancer : Treatment decisions in HER2+ mBC. Breast Cancer Res Treat. 2018;168(1):197-205. doi: 10.1007/s10549-017-4567-z
  58. Sanglier T, Ross R, Shi T, et al. Trastuzumab-based regimens beyond progression: A crucial treatment option for HER2+ advanced/metastatic breast cancer. Breast. 2022;66:262-71. doi: 10.1016/j.breast.2022.10.008
  59. Han Y, Wang J, Liu W, et al. Trastuzumab treatment after progression in HER2-positive metastatic breast cancer following relapse of trastuzumabbased regimens: a meta-analysis. Cancer Manag Res. 2019;11:4699-706. doi: 10.2147/CMAR.S198962
  60. Fruman DA, Rommel C. PI3K and cancer: lessons, challenges and opportunities. Nat Rev Drug Discov. 2014;13(2):140-56. doi: 10.1038/nrd4204
  61. Fu X, Creighton CJ, Biswal NC, et al. Overcoming endocrine resistance due to reduced PTEN levels in estrogen receptor-positive breast cancer by co-targeting mammalian target of rapamycin, protein kinase B, or mitogen-activated protein kinase kinase. Breast Cancer Res. 2014;16(5):430. doi: 10.1186/s13058-014-0430-x
  62. André F, O'Regan R, Ozguroglu M, et al. Everolimus for women with trastuzumabresistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2014;15(6):580-91. doi: 10.1016/S1470-2045(14)70138-X
  63. Tapia M, Hernando C, Martínez MT, et al. Clinical Impact of New Treatment Strategies for HER2-Positive Metastatic Breast Cancer Patients with Resistance to Classical Anti-HER Therapies. Cancers (Basel). 2023;15(18). doi: 10.3390/cancers15184522
  64. Mercogliano MF, Bruni S, Mauro FL, Schillaci R. Emerging Targeted Therapies for HER2-Positive Breast Cancer. Cancers (Basel). 2023;15(7). doi: 10.3390/cancers15071987
  65. Oberkampf F, Gutierrez M, Trabelsi Grati O, et al. Phase II study of intrathecal administration of trastuzumab in patients with HER2-positive breast cancer with leptomeningeal metastasis. Neuro Oncol. 2023;25(2):365-74. doi: 10.1093/neuonc/noac180
  66. Lemery SJ, Ricci MS, Keegan P, et al. FDA's Approach to Regulating Biosimilars. Clin Cancer Res. 2017;23(8):1882-5. doi: 10.1158/1078-0432.CCR-16-1354
  67. O'Callaghan J, Barry SP, Bermingham M, et al. Regulation of biosimilar medicines and current perspectives on interchangeability and policy. Eur J Clin Pharmacol. 2019;75(1):1-11. doi: 10.1007/s00228-018-2542-1
  68. Triantafyllidi E, Triantafillidis JK. Systematic Review on the Use of Biosimilars of Trastuzumab in HER2+ Breast Cancer. Biomedicines. 2022;10(8). doi: 10.3390/biomedicines10082045

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. HER2 signaling pathway [4].

Download (227KB)
Indexing metadata
3. Fig.1

Download (9KB)
Indexing metadata
4. Fig.2

Download (10KB)
Indexing metadata
5. Fig. 2. Mechanism of action of the anti-tumor conjugate: A – binding of the antibody to the extracellular domain of the HER2 receptor; B – formation of the endosome; C – lysosomal degradation of the endosome, release of the drug into the cytoplasm; D – implementation of the cytotoxic effect [31].

Download (200KB)
Indexing metadata
6. Fig. 3. The median overall survival demonstrated in pretreated patients with HER2+ mBC when trastuzumab was added to cytostatic agents [58].

Download (89KB)
Indexing metadata
7. Fig. 4. Forest plot: time to progression [59].

Download (53KB)
Indexing metadata
8. Fig. 5. Forest plot: OS [59].

Download (76KB)
Indexing metadata

Copyright (c) 2025 Consilium Medicum

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
 


Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».