Значение мутации в гене ESR1 при выборе терапии HR+/HER2- метастатического рака молочной железы

Значение мутации в гене ESR1 при выборе терапии HR+/HER2- метастатического рака молочной железы

Пайчадзе А.А., Чашникова Е.П., Голубева С.А. Значение мутации в гене ESR1 при выборе терапии HR+/HER2- метастатического рака молочной железы. Современная Онкология. 2024;26(4):410–413. DOI: 10.26442/18151434.2024.4.202990

© ООО «КОНСИЛИУМ МЕДИКУМ», 2024 г.

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Paichadze AA, Chashnikova EP, Golubeva SA. The role of ESR1 gene mutation in therapy selection for HR+/HER2- metastatic breast cancer: A review. Journal of Modern Oncology. 2024;26(4):410–413. DOI: 10.26442/18151434.2024.4.202990

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Аннотация

Экспрессия рецепторов эстрогенов выявляется более чем в 70% случаев метастатического рака молочной железы (мРМЖ). Эндокринотерапия является ключевой опцией лечения пациенток с гормонозависимым (HR+) HER2-негативным (HER2-) мРМЖ, однако проблема развития гормонорезистентности весьма актуальна, особенно на поздних линиях лечения. Одна из распространенных причин резистентности – возникновение мутаций в гене ESR1, которые в первичной опухоли обычно отсутствуют. Появление этих мутаций ухудшает течение болезни. До недавнего времени их определение носило лишь прогностическое значение и не учитывалось при выборе лечебного режима. В связи с появлением новых данных о роли мутаций в гене ESR1 и возможном их влиянии на выбор терапии мРМЖ представляется целесообразным рассмотреть основные критерии для выполнения анализа на мутации в рутинной практике, а также применяемые методики анализа. В обзорной статье затронуты вопросы, касающиеся оптимальных вариантов лечения при прогрессировании HR+/HER2- мРМЖ на фоне эндокринной терапии с учетом накопленных данных о мутациях в гене ESR1. Кроме того, рассмотрены имеющиеся данные по исследуемым пероральным селективным деструкторам эстрогеновых рецепторов (SERD), препаратам, существенно повышающим выживаемость на поздних линиях терапии гормонозависимых опухолей.

Ключевые слова: метастатический рак молочной железы, гормональная терапия, мутации в гене ESR1, жидкостная биопсия, циркулирующая опухолевая ДНК, селективные пероральные деструкторы рецепторов эстрогена, SERD

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Estrogen receptors are detected in more than 70% of cases of metastatic breast cancer (mBC). Currently, various hormonal therapy options are used to treat these tumors. However, modern oncology faces an acute problem of acquired resistance to hormonal therapy, including late lines of therapy for HR-positive (HR+) and HER2-negative (HER2-) mBC. The common causes of resistance include mutations in the ESR1 gene that are usually absent in the primary tumor. These mutations are associated with aggravation of the disease. Until recently, their detection was only of prognostic value and was not taken into account when choosing the treatment regimen. As the new data become available on the role of mutations in the ESR1 gene and their possible impact on the choice of mBC therapy, it seems appropriate to consider the main criteria for testing and test methods to detect the mutations in routine clinical practice. This review article addresses issues related to optimal treatment for progression of HR+/HER2- mBC during endocrine therapy, taking into account the accumulated data on mutations in the ESR1 gene. We also consider the available data on the studied oral selective estrogen receptor destructors as drugs that significantly increase survival in late lines of therapy for hormone-dependent tumors.

Keywords: metastatic breast cancer, hormonal therapy, ESR1 gene mutations, liquid biopsy, ctDNA, selective oral estrogen receptor destructors, SERD

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Список литературы

1. Martin LA, Riba R, Simigdala N, et al. Discovery of naturally occurring ESR1 mutations in breast cancer cell lines modelling endocrine resistance. Nat Commun. 2017;8:1865. DOI:10.1038/s41467-017-01864-y
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2016;34(25):2961-8. DOI:10.1200/JCO.2016.67.3061
13. Reinert T, Saad ED, Barrios CH, et al. Clinical Implications of ESR1 Mutations in Hormone Receptor-Positive Advanced Breast Cancer. Front Oncol. 2017;7:26. DOI:10.3389/fonc.2017.00026
14. Zundelevich A, Dadiani M, Kahana-Edwin S, et al. ESR1 mutations are frequent in newly diagnosed metastatic and loco-regional recurrence of endocrine-treated breast cancer and carry worse prognosis. Breast Cancer Res. 2020;22(1):16. DOI:10.1186/s13058-020-1246-5
15. Tolaney SM, Chan A, Petrakova K, et al. AMEERA-3: Randomized Phase II Study of Amcenestrant (Oral Selective Estrogen Receptor Degrader) Versus Standard Endocrine Monotherapy in Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer. J Clin Oncol.
2023;41(24):4014-24. DOI:10.1200/JCO.22.02746
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20. FDA approves elacestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. The US Food and Drug Agency. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-elacestrant-er-positive-.... Accessed: 27.09.2024.
21. Burstein HB, DeMichele A, Somerfield MR, et al. Testing for ESR1 Mutations to Guide Therapy for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer: ASCO Guideline Rapid Recommendation Update. J Clin Oncol. 2023;41:3423-5. DOI:10.1200/JCO.23.00638
22. Oliveira M, Pominchuk D, Nowecki Z, et al. Camizestrant, a next-generation oral SERD, vs fulvestrant in post-menopausal women with advanced ER-positive HER2-negative breast cancer: Results of the randomized, multi-dose phase 2 SERENA-2 trial. 2022 San Antonio Breast Cancer Symposium. Abstract GS3-02. Presented December 8, 2022.
23. Turner N, Huang-Bartlett C, Kalinsky K, et al. Design of SERENA-6, a phase III switching trial of camizestrant in ESR1-mutant breast cancer during first-line treatment. Future Oncol. 2023;19(8):559-73. DOI:10.2217/fon-2022-1196
24. Venetis K, Pepe F, Pescia C, et al. ESR1 mutations in HR+/HER2-metastatic breast cancer: Enhancing the accuracy of ctDNA testing. Cancer Treat Rev. 2023;121:102642. DOI:10.1016/j.ctrv.2023.102642
25. Bidard FC, Hardy-Bessard AC, Dalenc F, et al. PADA-1 investigators. Switch to fulvestrant and palbociclib versus no switch in advanced breast cancer with rising ESR1 mutation during aromatase inhibitor and palbociclib therapy (PADA-1): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2022;23(11):1367-77. DOI:10.1016/S1470-2045(22)00555-1
26. Johnston SR, Kilburn LS, Ellis P, et al. Fulvestrant plus anastrozole or placebo versus exemestane alone after progression on non-steroidal aromatase inhibitors in postmenopausal patients with hormone-receptor-positive locally advanced or metastatic breast cancer (SoFEA): a composite, multicentre, phase 3 randomised trial. Lancet Oncol.
2013;14(10):989-98. DOI:10.1016/S1470-2045(13)70322-X
27. Martin M, Zielinski C, Ruiz-Borrego M, et al. Prognostic and predictive value of ESR1 mutations in postmenopausal metastatic breast cancer (MBC) patients (pts) resistant to aromatase inhibitors (AI), treated with palbociclib (PAL) in combination with endocrine therapy (ET) or capecitabine (CAP) in the PEARL study. J Clin Oncol. 2020;38(15):1022. DOI:10.1200/JCO.2020.38.15_suppl.1022

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1. Martin LA, Riba R, Simigdala N, et al. Discovery of naturally occurring ESR1 mutations in breast cancer cell lines modelling endocrine resistance. Nat Commun. 2017;8:1865. DOI:10.1038/s41467-017-01864-y
2. Rak molochnoi zhelezy. Klinicheskie rekomendatsii Minzdrava RF. 2021 (in Russian).
3. Kolyadina IV, Poddubnaya IV. ESR1 mutation as potential predictive marker for choice of treatment tactics in hormone-resistant HR+/HER2-negative breast cancer. Medical Alphabet. 2020;(29):68-73 (in Russian). DOI:10.33667/2078-5631-2020-29-61-73
4. Toy W, Shen Y, Won H, et al. ESR1 ligand-binding domain mutations in hormone-resistant breast cancer. Nat Genet. 2013;45(12):1439-45. DOI:10.1038/ng.2822
5. Jeselsohn R, Buchwalter G, De Angelis C, et al. ESR1 mutations – a mechanism for acquired endocrine resistance in breast cancer. Nat Rev Clin Oncol.
2015;12(10):573-83. DOI:10.1038/nrclinonc.2015.117
6. Hortobagyi GN, Chen D, Piccart M, et al. Correlative Analysis of Genetic Alterations and Everolimus Benefit in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From BOLERO-2. J Clin Oncol. 2016;34(5):419-26. DOI:10.1200/JCO.2014.60.1971
7. Wang P, Bahreini A, Gyanchandani R, et al. Sensitive Detection of Mono- and Polyclonal ESR1 Mutations in Primary Tumors, Metastatic Lesions, and Cell-Free DNA of Breast Cancer Patients. Clin Cancer Res. 2016;22(5):1130-7. DOI:10.1158/1078-0432.CCR-15-1534
8. Schiavon G, Hrebien S, Garcia-Murillas I, et al. Analysis of ESR1 mutation in circulating tumor DNA demonstrates evolution during therapy for metastatic breast cancer. Sci Transl Med. 2015;7(313):313ra182. DOI:10.1126/scitranslmed.aac7551
9. Li X. Clinical Implications of Monitoring ESR1 Mutations by Circulating Tumor DNA in Estrogen Receptor Positive Metastatic Breast Cancer: A Pilot Study. Transl Oncol. 2020;13(2):321-8. DOI:10.1016/j.tranon.2019.11.007
10. Kuang Y, Siddiqui B, Hu J, et al. Unraveling the clinicopathological features driving the emergence of ESR1 mutations in metastatic breast cancer. NPJ Breast Cancer. 2018;4:22. DOI:10.1038/s41523-018-0075-5
11. Chandarlapaty S, Chen D, Wei He W, et al. Prevalence of ESR1 Mutations in Cell-Free DNA and Outcomes in Metastatic Breast Cancer: A Secondary Analysis of the BOLERO‑2 Clinical Trial. JAMA Oncol. 2016;2(10):1310-5. DOI:10.1001/jamaoncol.2016.1279
12. Fribbens C, O’Leary B, Kilburn L, et al. Plasma ESR1 Mutations and the Treatment of Estrogen Receptor-Positive Advanced Breast Cancer. J Clin Oncol.
2016;34(25):2961-8. DOI:10.1200/JCO.2016.67.3061
13. Reinert T, Saad ED, Barrios CH, et al. Clinical Implications of ESR1 Mutations in Hormone Receptor-Positive Advanced Breast Cancer. Front Oncol. 2017;7:26. DOI:10.3389/fonc.2017.00026
14. Zundelevich A, Dadiani M, Kahana-Edwin S, et al. ESR1 mutations are frequent in newly diagnosed metastatic and loco-regional recurrence of endocrine-treated breast cancer and carry worse prognosis. Breast Cancer Res. 2020;22(1):16. DOI:10.1186/s13058-020-1246-5
15. Tolaney SM, Chan A, Petrakova K, et al. AMEERA-3: Randomized Phase II Study of Amcenestrant (Oral Selective Estrogen Receptor Degrader) Versus Standard Endocrine Monotherapy in Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer. J Clin Oncol.
2023;41(24):4014-24. DOI:10.1200/JCO.22.02746
16. Martín M, Lim E, Chavez-MacGregor M, et al. Giredestrant for Estrogen Receptor-Positive, HER2-Negative, Previously Treated Advanced Breast Cancer: Results From the Randomized, Phase II acelERA Breast Cancer Study. J Clin Oncol. 2024;42(18):2149-60. DOI:10.1200/JCO.23.01500
17. Roche keeps expanding its SERD phase 3 programme. ApexOnco. Available at: https://www.oncologypipeline.com/apexonco/roche-keeps-expanding-its-serd-phase-3-programme. Accessed: 27.09.2024.
18. Bidard FC, Kaklamani VG, Neven P, et al. Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial. J Clin Oncol. 2022;40(28):3246-56. DOI:10.1200/JCO.22.00338
19. Kolyadina IV. Following in the footsteps of SABCS 2022: top 12 advanced breast cancer studies that could change our clinical practice: A review. Journal of Modern Oncology. 2023;25(1):46-54 (in Russian). DOI:10.26442/18151434.2023.1.202102
20. FDA approves elacestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. The US Food and Drug Agency. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-elacestrant-er-positive-.... Accessed: 27.09.2024.
21. Burstein HB, DeMichele A, Somerfield MR, et al. Testing for ESR1 Mutations to Guide Therapy for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer: ASCO Guideline Rapid Recommendation Update. J Clin Oncol. 2023;41:3423-5. DOI:10.1200/JCO.23.00638
22. Oliveira M, Pominchuk D, Nowecki Z, et al. Camizestrant, a next-generation oral SERD, vs fulvestrant in post-menopausal women with advanced ER-positive HER2-negative breast cancer: Results of the randomized, multi-dose phase 2 SERENA-2 trial. 2022 San Antonio Breast Cancer Symposium. Abstract GS3-02. Presented December 8, 2022.
23. Turner N, Huang-Bartlett C, Kalinsky K, et al. Design of SERENA-6, a phase III switching trial of camizestrant in ESR1-mutant breast cancer during first-line treatment. Future Oncol. 2023;19(8):559-73. DOI:10.2217/fon-2022-1196
24. Venetis K, Pepe F, Pescia C, et al. ESR1 mutations in HR+/HER2-metastatic breast cancer: Enhancing the accuracy of ctDNA testing. Cancer Treat Rev. 2023;121:102642. DOI:10.1016/j.ctrv.2023.102642
25. Bidard FC, Hardy-Bessard AC, Dalenc F, et al. PADA-1 investigators. Switch to fulvestrant and palbociclib versus no switch in advanced breast cancer with rising ESR1 mutation during aromatase inhibitor and palbociclib therapy (PADA-1): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2022;23(11):1367-77. DOI:10.1016/S1470-2045(22)00555-1
26. Johnston SR, Kilburn LS, Ellis P, et al. Fulvestrant plus anastrozole or placebo versus exemestane alone after progression on non-steroidal aromatase inhibitors in postmenopausal patients with hormone-receptor-positive locally advanced or metastatic breast cancer (SoFEA): a composite, multicentre, phase 3 randomised trial. Lancet Oncol.
2013;14(10):989-98. DOI:10.1016/S1470-2045(13)70322-X
27. Martin M, Zielinski C, Ruiz-Borrego M, et al. Prognostic and predictive value of ESR1 mutations in postmenopausal metastatic breast cancer (MBC) patients (pts) resistant to aromatase inhibitors (AI), treated with palbociclib (PAL) in combination with endocrine therapy (ET) or capecitabine (CAP) in the PEARL study. J Clin Oncol. 2020;38(15):1022. DOI:10.1200/JCO.2020.38.15_suppl.1022

Авторы

А.А. Пайчадзе*¹, Е.П. Чашникова², С.А. Голубева¹

¹ФГБУ «Национальный медицинский исследовательский центр радиологии» Минздрава России, Москва, Россия;
²Индивидуальный предприниматель
*paiann@mail.ru

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Anna A. Paichadze*¹, Ekaterina P. Chashnikova², Sofya A. Golubeva¹

¹National Medical Research Radiological Centre, Moscow, Russia;
²Individual entrepreneur
*paiann@mail.ru

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