Andreev DA, Zavyalov AA. Triple-negative breast cancer: new options for systemic targeted therapy. A review. Journal of Modern Oncology. 2022;24(3):368–372. DOI: 10.26442/18151434.2022.3.201767
Рак молочной железы с тройным негативным фенотипом: новые опции системной таргетной терапии
Андреев Д.А., Завьялов А.А. Рак молочной железы с тройным негативным фенотипом: новые опции системной таргетной терапии. Современная Онкология. 2022;24(3):368–372.
DOI: 10.26442/18151434.2022.3.201767
Andreev DA, Zavyalov AA. Triple-negative breast cancer: new options for systemic targeted therapy. A review. Journal of Modern Oncology. 2022;24(3):368–372. DOI: 10.26442/18151434.2022.3.201767
Обоснование. У 15–20% больных рак молочной железы характеризуется отсутствием или незначительной экспрессией в злокачественных клетках молекулярных терапевтических мишеней-рецепторов трех ключевых типов: эстрогеновые рецепторы, прогестероновые рецепторы, рецепторы-2 эпидермального фактора роста человека (тройной негативный фенотип рака молочной железы – ТНРМЖ). В 2021 г. на конференциях Американского и Европейского обществ клинической онкологии (ASCO и ESMO), а также Симпозиуме по раку молочной железы в Сан-Антонио (SABCS), проходившем с 7 по 10 декабря, озвучены важные достижения, касающиеся новых подходов к лечению неоднородной фракции больных ТНРМЖ. Цель. Найти и обобщить наиболее яркие итоги клинических исследований новых опций лечения больных ТНРМЖ по результатам работы SABCS – 2021. Материалы и методы. Научное исследование выполнено по результатам поиска в базах цифровой медицинской образовательной платформы MEDtalks (Хилверсюм, Нидерланды) и базе PubMed/Medline. Анализировали результаты, опубликованные в 2021–2022 гг. Результаты. Систематизированы некоторые итоги современных клинических исследований, посвященных лекарственной терапии пациентов с ТНРМЖ, дискутировавшиеся на SABCS – 2021 (7–10 декабря, Сан-Антонио, США). В настоящее время в мире получены многообещающие результаты инновационных клинических исследований по определению действенных подходов к выбору дифференцированной таргетной и иммунотерапии для лечения больных ТНРМЖ: OlympiA, KEYNOTE-522, cTRAK TN II фазы, KEYNOTE-355, NIMBUS, исследование I фазы TROPION. Заключение. Принимая во внимание молекулярную и гистологическую неоднородность ТНРМЖ, является целесообразным выделение подгрупп больных с определенными количественными и качественными клиническими характеристиками для дальнейшей идентификации эффективных схем персонифицированного лечения. Проведение дополнительных клинических исследований и многофакторный анализ данных в подгруппах больных ТНРМЖ, а также индивидуализированных историй лечения путем применения современных методологических инструментов позволит приблизить решение задач по ведению данной категории больных.
Background. In 15-20% of patients, breast cancer is characterized by the absence or negligible expression in malignant cells of molecular therapeutic receptor targets of three key types: estrogen receptors, progesterone receptors, human epidermal growth factor receptor-2 (triple negative breast cancer – TNBC). At the 2021 conferences of the American and European Societies of Clinical Oncology (ASCO and ESMO) and the San Antonio Breast Cancer Symposium (SABCS), held from December 7 to 10, important advances in new approaches to the treatment of heterogeneous TNBC cohort were announced. Aim. To find and summarize the most striking results of clinical studies on new treatment options for TNBC patients based on the SABCS 2021.
Materials and methods. We searched the databases of the digital medical education platform MEDtalks (Hilversum, The Netherlands) and the PubMed/Medline database and analyzed the results published in 2021-2022. Results. We systematized some results of clinical studies on drug therapy in patients with TNBC, discussed at SABCS 2021 (December 7-10, San Antonio, USA). There are now promising results from innovative clinical studies worldwide to identify the optimal approach to the selection of differentiated targeted and immunotherapies for the treatment of TNBC patients: OlympiA, KEYNOTE-522, cTRAK TN Phase II, KEYNOTE-355, NIMBUS, TROPION Phase I study. Conclusion. Considering the molecular and histological heterogeneity of TNBC, it is reasonable to identify subgroups of patients with some quantitative and qualitative clinical characteristics for further identification of effective personalized treatment regimens. Additional clinical studies and multivariate analysis of data in the subgroups of patients with TNBC, as well as individualized treatment cases, using current methodological tools will contribute to solving the issues in the management of this category of patients.
1. Злокачественные новообразования в России в 2019 году (заболеваемость и смертность). Под ред. А.Д. Каприна, В.В. Старинского, А.О. Шахзадовой. М.: МНИОИ им. П.А. Герцена – филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2020 [Zlokachestvennye novoobrazovaniia v Rossii v 2019 godu (zabolevaemost' i smertnost'). Pod red. AD Kaprina, VV Starinskogo, AO Shakhzadovoi. Moscow: MNIOI im. P.A. Gertsena − filial FGBU "NMITs radiologii" Minzdrava Rossii, 2020 (in Russian)].
2. Андреев Д.А., Кашурников А.Ю., Завьялов А.А. Клинически значимые молекулярные маркеры в новой дифференцированной терапии рака молочной железы с тройным негативным фенотипом (РМЖ эр-/пр-/HER2-). Сборник научных трудов. М.: НИИОЗММ, 2020; c. 89-94 [Andreev DA, Kashurnikov AIu, Zav'ialov AA. Klinicheski znachimye molekuliarnye markery v novoi differentsirovannoi terapii raka molochnoi zhelezy s troinym negativnym fenotipom (RMZh er-/pr-/HER2-). Sbornik nauchnykh trudov. Moscow: NIIOZMM, 2020; p. 89-94 (in Russian)].
3. MEDtalks, Tol J, Jager A, Smorenburg C, Konings I. SABCS 2021 journaal deel 3. Triple negatief Mammacarcinoom. Published 2021. Available at: https://www.medtalks.nl/sabcs2021journaaldeel3. Accessed: 31.03.2022.
4. Altundag K. Some subgroups might get less benefit from adjuvant olaparib trial in high-risk, HER2-negative and germline BRCA2 BRCA1- or BRCA2-mutated early breast cancer patients. J BUON. 2021;26(5):2202.
5. Tutt ANJ, Garber JE, Kaufman B, et al. Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer. N Engl J Med. 2021;384(25):2394-405. DOI:10.1056/NEJMoa2105215
6. Adjuvant Olaparib Improves Disease-Free Survival in Early, High-Risk, BRCA-Mutated, HER2- Breast Cancer. Oncologist. 2021;26 Suppl 3(Suppl 3):S3-4. DOI:10.1002/onco.13863
7. Tutt ANJ, Garber J, Gelber RD, et al. VP1-2022: Pre-specified event driven analysis of Overall Survival (OS) in the OlympiA phase III trial of adjuvant olaparib (OL) in germline BRCA1/2 mutation (gBRCAm) associated breast cancer. Ann Oncol. 2022;33(5):566-8. DOI:10.1016/j.annonc.2022.03.008
8. Tarantino P, Corti C, Schmid P, et al. Immunotherapy for early triple negative breast cancer: research agenda for the next decade. NPJ Breast Cancer. 2022;8(1):23. DOI:10.1038/s41523-022-00386-1
9. Jacobson A. Pembrolizumab Improves Outcomes in Early-Stage and Locally Advanced or Metastatic Triple-Negative Breast Cancer. Oncologist. 2022;27(Supple. 1):S17-8. DOI:10.1093/oncolo/oyac014
10. National Library of Medicine. A Trial Using ctDNA Blood Tests to Detect Cancer Cells After Standard Treatment to Trigger Additional Treatment in Early Stage Triple Negative Breast Cancer Patients (c-TRAK-TN). Available at: https://clinicaltrials.gov/ct2/show/study/NCT03145961. Accessed: 04.04.2022.
11. Turner N, Swift C, Jenkins B, et al. Abstract GS3-06: Primary results of the cTRAK TN trial: A clinical trial utilising ctDNA mutation tracking to detect minimal residual disease and trigger intervention in patients with moderate and high risk early stage triple negative breast cancer. Cancer Res. 2022;82:GS3-06. DOI:10.1158/1538-7445.SABCS21-GS3-06
12. Sant M, Bernat-Peguera A, Felip E, Margelí M. Role of ctDNA in Breast Cancer. Cancers (Basel). 2022;14(2). DOI:10.3390/cancers14020310
13. Larribère L, Martens UM. Advantages and Challenges of Using ctDNA NGS to Assess the Presence of Minimal Residual Disease (MRD) in Solid Tumors. Cancers (Basel). 2021;13(22):5698. DOI:10.3390/cancers13225698
14. MEDtalks International, Verschoor N. SABCS 2021 Circulerende tumorcellen en tumor-DNA als prognostische biomarkers. Published 2022. Available at: https://www.medtalks.nl/sabcsnoortjeverschoor. Accessed: 19.05.2022.
15. Barroso-Sousa R, Trippa L, Lange P, et al. Nimbus: A phase II study of nivolumab plus ipilimumab in metastatic hypermutated HER2-negative breast cancer. J Clin Oncol. 2019;37(15_suppl):TPS1115. DOI:10.1200/JCO.2019.37.15\_suppl.TPS1115
16. Healio. Nivolumab plus ipilimumab shows benefit in metastatic HER2-negative breast cancer. Published 2021. Available at: https://www.healio.com/news/hematology-oncology/20211210/nivolumab-plus-ipilimumab-shows-benefit-in-.... Accessed: 04.04.2022.
17. Daiichi Sankyo and AstraZeneca. Datopotamab Deruxtecan Continues to Show Promising Durable Response and Disease Control in Patients with Metastatic Triple Negative Breast Cancer. Published 2021. Available at: https://www.daiichisankyo.com/files/news/pressrelease/pdf/202112/20211207_E2.pdf. Accessed: 04.04.2022.
18. Российское общество клинической онкологии (RUSSCO); Семиглазова Т.Ю., Шарашенидзе С.М. Новости в лекарственном лечении больных раком молочной железы по материалам виртуального конгресса ESMO2020. Published 2020. Режим доступа: https://rosoncoweb.ru. Сылка активна на 04.04.2022 [Russian Society of Clinical Oncology (RUSSCO); Semiglazova TYu, Sharashenidze SM. News in the drug treatment of patients with breast cancer based on the materials of the virtual congress ESMO2020. Published 2020. Available at: https://rosoncoweb.ru. Accessed: 04.04.2022 (in Russian)].
19. Cardoso F, Paluch-Shimon S, Senkus E, et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5). Ann Oncol Off J Eur Soc Med Oncol. 2020;31(12):1623-49. DOI:10.1016/j.annonc.2020.09.010
20. Daiichi Sankyo Inc. Datopotamab Deruxtecan Continues to Show Promising Durable Response and Disease Control in Patients with Metastatic Triple Negative Breast Cancer. Published 2021. Available at: https://www.bloomberg.com/press-releases/2021-12-07/datopotamab-deruxtecan-continues-to-show-promisi.... Accessed: 07.04.2022.
21. El Bairi K, Haynes HR, Blackley E, et al. The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group. NPJ Breast Cancer. 2021;7(1):150. DOI:10.1038/s41523-021-00346-1
22. Loi S, Salgado R, Adams S, et al. Tumor infiltrating lymphocyte stratification of prognostic staging of early-stage triple negative breast cancer. NPJ breast cancer. 2022;8(1):3. DOI:10.1038/s41523-021-00362-1
23. McAnena PF, McGuire A, Ramli A, et al. Breast cancer subtype discordance: impact on post-recurrence survival and potential treatment options. BMC Cancer. 2018;18(1):203. DOI:10.1186/s12885-018-4101-7
24. Boman C, Zerdes I, Mårtensson K, et al. Discordance of PD-L1 status between primary and metastatic breast cancer: A systematic review and meta-analysis. Cancer Treat Rev. 2021;99:102257. DOI:10.1016/j.ctrv.2021.102257
25. Yao JH, Zhang WQ, Shao Y, et al. Molecular phenotype discordance between primary and synchronous metastatic lesions of breast cancer and its determinant role in guiding treatment decisions: a case report. Am J Transl Res. 2020;12(9):5866-73.
________________________________________________
1. Zlokachestvennye novoobrazovaniia v Rossii v 2019 godu (zabolevaemost' i smertnost'). Pod red. AD Kaprina, VV Starinskogo, AO Shakhzadovoi. Moscow: MNIOI im. P.A. Gertsena − filial FGBU "NMITs radiologii" Minzdrava Rossii, 2020 (in Russian).
2. Andreev DA, Kashurnikov AIu, Zav'ialov AA. Klinicheski znachimye molekuliarnye markery v novoi differentsirovannoi terapii raka molochnoi zhelezy s troinym negativnym fenotipom (RMZh er-/pr-/HER2-). Sbornik nauchnykh trudov. Moscow: NIIOZMM, 2020; p. 89-94 (in Russian).
3. MEDtalks, Tol J, Jager A, Smorenburg C, Konings I. SABCS 2021 journaal deel 3. Triple negatief Mammacarcinoom. Published 2021. Available at: https://www.medtalks.nl/sabcs2021journaaldeel3. Accessed: 31.03.2022.
4. Altundag K. Some subgroups might get less benefit from adjuvant olaparib trial in high-risk, HER2-negative and germline BRCA2 BRCA1- or BRCA2-mutated early breast cancer patients. J BUON. 2021;26(5):2202.
5. Tutt ANJ, Garber JE, Kaufman B, et al. Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer. N Engl J Med. 2021;384(25):2394-405. DOI:10.1056/NEJMoa2105215
6. Adjuvant Olaparib Improves Disease-Free Survival in Early, High-Risk, BRCA-Mutated, HER2- Breast Cancer. Oncologist. 2021;26 Suppl 3(Suppl 3):S3-4. DOI:10.1002/onco.13863
7. Tutt ANJ, Garber J, Gelber RD, et al. VP1-2022: Pre-specified event driven analysis of Overall Survival (OS) in the OlympiA phase III trial of adjuvant olaparib (OL) in germline BRCA1/2 mutation (gBRCAm) associated breast cancer. Ann Oncol. 2022;33(5):566-8. DOI:10.1016/j.annonc.2022.03.008
8. Tarantino P, Corti C, Schmid P, et al. Immunotherapy for early triple negative breast cancer: research agenda for the next decade. NPJ Breast Cancer. 2022;8(1):23. DOI:10.1038/s41523-022-00386-1
9. Jacobson A. Pembrolizumab Improves Outcomes in Early-Stage and Locally Advanced or Metastatic Triple-Negative Breast Cancer. Oncologist. 2022;27(Supple. 1):S17-8. DOI:10.1093/oncolo/oyac014
10. National Library of Medicine. A Trial Using ctDNA Blood Tests to Detect Cancer Cells After Standard Treatment to Trigger Additional Treatment in Early Stage Triple Negative Breast Cancer Patients (c-TRAK-TN). Available at: https://clinicaltrials.gov/ct2/show/study/NCT03145961. Accessed: 04.04.2022.
11. Turner N, Swift C, Jenkins B, et al. Abstract GS3-06: Primary results of the cTRAK TN trial: A clinical trial utilising ctDNA mutation tracking to detect minimal residual disease and trigger intervention in patients with moderate and high risk early stage triple negative breast cancer. Cancer Res. 2022;82:GS3-06. DOI:10.1158/1538-7445.SABCS21-GS3-06
12. Sant M, Bernat-Peguera A, Felip E, Margelí M. Role of ctDNA in Breast Cancer. Cancers (Basel). 2022;14(2). DOI:10.3390/cancers14020310
13. Larribère L, Martens UM. Advantages and Challenges of Using ctDNA NGS to Assess the Presence of Minimal Residual Disease (MRD) in Solid Tumors. Cancers (Basel). 2021;13(22):5698. DOI:10.3390/cancers13225698
14. MEDtalks International, Verschoor N. SABCS 2021 Circulerende tumorcellen en tumor-DNA als prognostische biomarkers. Published 2022. Available at: https://www.medtalks.nl/sabcsnoortjeverschoor. Accessed: 19.05.2022.
15. Barroso-Sousa R, Trippa L, Lange P, et al. Nimbus: A phase II study of nivolumab plus ipilimumab in metastatic hypermutated HER2-negative breast cancer. J Clin Oncol. 2019;37(15_suppl):TPS1115. DOI:10.1200/JCO.2019.37.15\_suppl.TPS1115
16. Healio. Nivolumab plus ipilimumab shows benefit in metastatic HER2-negative breast cancer. Published 2021. Available at: https://www.healio.com/news/hematology-oncology/20211210/nivolumab-plus-ipilimumab-shows-benefit-in-.... Accessed: 04.04.2022.
17. Daiichi Sankyo and AstraZeneca. Datopotamab Deruxtecan Continues to Show Promising Durable Response and Disease Control in Patients with Metastatic Triple Negative Breast Cancer. Published 2021. Available at: https://www.daiichisankyo.com/files/news/pressrelease/pdf/202112/20211207_E2.pdf. Accessed: 04.04.2022.
18. Russian Society of Clinical Oncology (RUSSCO); Semiglazova TYu, Sharashenidze SM. News in the drug treatment of patients with breast cancer based on the materials of the virtual congress ESMO2020. Published 2020. Available at: https://rosoncoweb.ru. Accessed: 04.04.2022 (in Russian).
19. Cardoso F, Paluch-Shimon S, Senkus E, et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5). Ann Oncol Off J Eur Soc Med Oncol. 2020;31(12):1623-49. DOI:10.1016/j.annonc.2020.09.010
20. Daiichi Sankyo Inc. Datopotamab Deruxtecan Continues to Show Promising Durable Response and Disease Control in Patients with Metastatic Triple Negative Breast Cancer. Published 2021. Available at: https://www.bloomberg.com/press-releases/2021-12-07/datopotamab-deruxtecan-continues-to-show-promisi.... Accessed: 07.04.2022.
21. El Bairi K, Haynes HR, Blackley E, et al. The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group. NPJ Breast Cancer. 2021;7(1):150. DOI:10.1038/s41523-021-00346-1
22. Loi S, Salgado R, Adams S, et al. Tumor infiltrating lymphocyte stratification of prognostic staging of early-stage triple negative breast cancer. NPJ breast cancer. 2022;8(1):3. DOI:10.1038/s41523-021-00362-1
23. McAnena PF, McGuire A, Ramli A, et al. Breast cancer subtype discordance: impact on post-recurrence survival and potential treatment options. BMC Cancer. 2018;18(1):203. DOI:10.1186/s12885-018-4101-7
24. Boman C, Zerdes I, Mårtensson K, et al. Discordance of PD-L1 status between primary and metastatic breast cancer: A systematic review and meta-analysis. Cancer Treat Rev. 2021;99:102257. DOI:10.1016/j.ctrv.2021.102257
25. Yao JH, Zhang WQ, Shao Y, et al. Molecular phenotype discordance between primary and synchronous metastatic lesions of breast cancer and its determinant role in guiding treatment decisions: a case report. Am J Transl Res. 2020;12(9):5866-73.
Авторы
Д.А. Андреев*1, А.А. Завьялов1,2
1 ГБУ города Москвы «Научно-исследовательский институт организации здравоохранения и медицинского менеджмента Департамента здравоохранения города Москвы», Москва, Россия;
2 ФГБУ «Государственный научный центр РФ – Федеральный медицинский биофизический центр им. А.И. Бурназяна» ФМБА России, Москва, Россия
*AndreevDA@zdrav.mos.ru
________________________________________________
Dmitry A. Andreev*1, Aleksandr A. Zavyalov1,2
1 Research Institute for Healthcare Organization and Medical Management of Moscow Healthcare Department, Moscow, Russia;
2 Russian State Research Center − Burnasyan Federal Medical Biophysical Center, Moscow, Russia
*AndreevDA@zdrav.mos.ru