medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2022-16-9-57-64medsovet-6917Research ArticleТАРГЕТНАЯ ТЕРАПИЯTARGET THERAPY OF TUMORSТерапия алпелисибом: от теории к практикеAlpelisib therapy: from theory to practicehttps://orcid.org/0000-0001-5289-7866ЛубенниковаЕ. В.LubennikovaE. V.

Лубенникова Елена Владимировна – кандидат медицинских наук, старший научный сотрудник онкологического отделения лекарственных методов лечения (химиотерапевтического) №1, Научно-исследовательский институт клинической онкологии имени академика РАН и РАМН Н.Н. Трапезникова.

115478, Москва, Каширское шоссе, д. 24.

Elena V. Lubennikova - Cand. Sci. (Med.), Senior Researcher, Chemotherapy Department No. 1, Research Institute of Clinical Oncology named after N.N. Trapeznikova, Blokhin National Medical Research Center of Oncology.

24, Kashirskoye Shosse, Moscow, 115478.

lubennikova@yandex.ruhttps://orcid.org/0000-0002-5039-6360ТитоваТ. А.TitovaT. A.

Титова Татьяна Александровна - врач-онколог онкологического отделения лекарственных методов лечения (химиотерапевтического) №1, Научно-исследовательский институт клинической онкологии имени академика РАН и РАМН Н.Н. Трапезникова.

115478, Москва, Каширское шоссе, д. 24.

Tatyana A. Titova - Oncologist, Chemotherapy Department No. 1, Research Institute of Clinical Oncology named after N.N. Trapeznikova, Blokhin National Medical Research Center of Oncology.

24, Kashirskoye Shosse, Moscow, 115478.

tatiana.titovadoc@gmail.comhttps://orcid.org/0000-0002-0105-9376ГаньшинаИ. П.GanshinaI. P.

Ганьшина Инна Петровна - кандидат медицинских наук, ведущий научный сотрудник онкологического отделения лекарственных методов лечения (химиотерапевтического) №1, Научно-исследовательский институт клинической онкологии имени академика РАН и РАМН Н.Н. Трапезникова.

115478, Москва, Каширское шоссе, д. 24.

Inna P. Ganshina - Cand. Sci. (Med.), Leading Researcher, Chemotherapy Department No. 1, Research Institute of Clinical Oncology named after N.N. Trapeznikova Blokhin National Medical Research Center of Oncology.

24, Kashirskoye Shosse, Moscow, 115478.

ganshinainna77@mail.ruНациональный медицинский исследовательский центр онкологии имени Н.Н. БлохинаРоссияBlokhin National Medical Research Center of OncologyRussian Federation202218062022095764Copyright © Лубенникова Е.В., Титова Т.А., Ганьшина И.П., 20222022Лубенникова Е.В., Титова Т.А., Ганьшина И.П.Lubennikova E.V., Titova T.A., Ganshina I.P.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/6917

До разработки и внедрения в широкую практику первого Р13К-ингибитора (алпелисиб) наличие мутации в гене PIK3CA имело лишь прогностическое значение: оно определяло неблагоприятное течение люминального HER2-не-гативного (HR+HER2-) метастатического рака молочной железы (мРМЖ) (тестирование на мутации не входило в рутинные методы обследования). Достижения в лечении HR+HER2- мРМЖ связаны, в первую очередь, с применением ингибиторов CDK4/6, позволивших не только значимо увеличить медиану времени без прогрессирования при сохранении высокого качества жизни, но и достоверно увеличить продолжительность жизни пациентов с HR+HER2- мРМЖ. Однако подгрупповые анализы демонстрируют, что наличие мутации PIK3CA является независимым фактором снижения показателей времени без прогрессирования и общей выживаемости даже у больных, получавших ингибиторы CDK4/6. Мутации гена PIK3CA диагностируются у 30-40% больных люминальным мРМЖ, они сопряжены с повышенным риском рецидива и прогрессии болезни, ассоциируются со значимым снижением показателей выживаемости и эффективности лечения, определяют развитие первичной и вторичной резистентности к эндокринотерапии. Комбинированная с алпелисибом стандартная эндокринотерапия фулвестрантом позволила значимо улучшить результаты лечения пациентов с HR+HER2-мРМЖ c мутацией PIK3CA, ранее получавших лечение по поводу распространенной болезни или имевших прогрессирование во время адъювантной терапии. В настоящее время данная комбинация вошла во все основные международные рекомендации и является приоритетной опцией терапии. Тестирование на наличие мутаций PIK3CA - современный стандарт диагностики при люминальном HER2- мРМЖ. В обзоре представлены обновленные данные основных клинических исследований алпелисиба, результаты лечения из реальной клинической практики, рассмотрены аспекты применения препарата у пациентов с различным анамнезом. В статье обозначены основные рекомендации по профилактике и коррекции нежелательных явлений, представлен собственный опыт применения алпелисиба у больной с классическим течением РМЖ с мутацией PIK3CA.

Before the development and implementation of the first PI3K inhibitor (alpelisib), the presence of a mutation in the PIK3CA gene had only prognostic value: it determined the unfavorable course of luminal HER2-negative metastatic breast cancer (testing for mutations was not part of routine screening methods). Achievements in the treatment of HR+HER2- mBC are primarily associated with the use of CDK4/6 inhibitors, which allowed not only a significant increase in the median progression-free survival while maintaining high quality of life, but also significantly increased overall survival of patients with luminal HER2-negative metastatic breast cancer. However, subgroup analyses demonstrate that the presence of the PIK3CA mutation is an independent factor in decreasing progression-free time and overall survival, even in patients treated with CDK4/6 inhibitors. Mutations of the PIK3CA gene are diagnosed in 30-40% of luminal metastatic breast cancer patients, they are associated with an increased risk of relapse and disease progression, are associated with a significant reduction in survival rates and treatment effectiveness, and determine the development of primary and secondary resistance to endocrine therapy. Standard endocrine therapy with fulvestrant combined with alpelisib has significantly improved treatment outcomes in patients with HR+HER2-metastatic breast cancer with the PIK3CA mutation who previously received treatment for advanced disease or had progression during adjuvant therapy. This combination is now included in all major international guidelines and is a priority therapy option. Testing for PIK3CA mutations is the current diagnostic standard in luminal HER2-negative mBC. The review presents an update of the main clinical trials with alpelisib, treatment results from real clinical practice, and also considers aspects of use in pretreated patients with different medical history. The article outlines the main recommendations for the prevention and correction of adverse events, and presents our own experience of using alpelisib in a patient with a classic course of breast cancer with a PIK3CA mutation.

мутация PIK3CAалпелисибфулвестрантметастатический рак молочной железылюминальный рак молочной железыэндокринотерапияэндокринорезистентностьPIK3CA mutationalpelisibfulvestrantmetastatic breast cancerluminal breast cancerendocrine therapyendocrine resistanceReferencesCardoso F., Paluch-Shimon S., Senkus E., Curigliano G., Aapro M. S., Andre F. et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5). Ann Oncol. 2020;31(12):1623-1649. https://doi.org/10.1016/j.annonc.2020.09.010.Cardoso F., Paluch-Shimon S., Senkus E., Curigliano G., Aapro M. S., Andre F. et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5). Ann Oncol. 2020;31(12):1623-1649. https://doi.org/10.1016/j.annonc.2020.09.010.Vasan N., Baselga J., Hyman D.M. A view on drug resistance in cancer. Nature. 2019;575(7782):299-309. https://doi.org/10.1038/s41586-019-1730-1.Vasan N., Baselga J., Hyman D.M. A view on drug resistance in cancer. Nature. 2019;575(7782):299-309. https://doi.org/10.1038/s41586-019-1730-1.Gomez T.Zj., Mao P., Alcon C., Kowalski K., Johnson G.N., Xu G. et al. Cell Line-Specific Network Models of ER+ Breast Cancer Identify Potential PI3Ka Inhibitor Resistance Mechanisms and Drug Combinations. Cancer Res. 2021;81(17):4603-4617. https://doi.org/10.1158/0008-5472.CAN-21-1208.Gomez T.Zj., Mao P., Alcon C., Kowalski K., Johnson G.N., Xu G. et al. Cell Line-Specific Network Models of ER+ Breast Cancer Identify Potential PI3Ka Inhibitor Resistance Mechanisms and Drug Combinations. Cancer Res. 2021;81(17):4603-4617. https://doi.org/10.1158/0008-5472.CAN-21-1208.Hanker A.B., Sudhan D.R., Arteaga C.L. Overcoming Endocrine Resistance in Breast Cancer. Cancer Cell. 2020;37(4):496-513. https://doi.org/10.1016/j.ccell.2020.03.009.Hanker A.B., Sudhan D.R., Arteaga C.L. Overcoming Endocrine Resistance in Breast Cancer. Cancer Cell. 2020;37(4):496-513. https://doi.org/10.1016/j.ccell.2020.03.009.Liu P., Cheng H., Roberts T.M., Zhao j.j. Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009;8(8):627-644. https://doi.org/10.1038/nrd2926.Liu P., Cheng H., Roberts T.M., Zhao j.j. Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009;8(8):627-644. https://doi.org/10.1038/nrd2926.Miller T.W., Balko j.M., Arteaga C.L. Phosphatidylinositol 3-kinase and antiestrogen resistance in breast cancer. J Clin Oncol. 2011;29(33):4452-4261. https://doi.org/10.1200/jco.2010.34.4879.Miller T.W., Balko j.M., Arteaga C.L. Phosphatidylinositol 3-kinase and antiestrogen resistance in breast cancer. J Clin Oncol. 2011;29(33):4452-4261. https://doi.org/10.1200/jco.2010.34.4879.Gao j.j., Cheng j., Bloomquist E., Sanchez j., Wedam S.B., Singh H. et al. CDK4/6 inhibitor treatment for patients with hormone receptor-positive, HER2-negative, advanced or metastatic breast cancer: a US Food and Drug Administration pooled analysis. Lancet Oncol. 2020;21(2):250-260. https://doi.org/10.1016/S1470-2045(19)30804-6.Gao j.j., Cheng j., Bloomquist E., Sanchez j., Wedam S.B., Singh H. et al. CDK4/6 inhibitor treatment for patients with hormone receptor-positive, HER2-negative, advanced or metastatic breast cancer: a US Food and Drug Administration pooled analysis. Lancet Oncol. 2020;21(2):250-260. https://doi.org/10.1016/S1470-2045(19)30804-6.Ганьшина И.П., Филоненко Д.А., Гордеева О.О., Лубенникова Е.В., Колядина И.В., Мещеряков А.А. Рибоциклиб в лечении гормонопозитивного HER2-негативного рака молочной железы. Медицинский совет. 2019;(10):72-80. https://doi.org/10.21518/2079-701X-2019-10-72-80.Ganshina I.P., Filonenko D.A., Gordeeva O.O., Lubennikova E.V., Kolyadina I.V., Mescheryakov A.A. Ribociclib for the treatment of hormone-positive HER2-negative breast cancer. Meditsinskiy Sovet. 2019;(10):72-80. (In Russ.) https://doi.org/10.21518/2079-701X-2019-10-72-80.Wang L., Gao S., Li D., Ran X., Sheng Z., Wu W., Yang X. CDK4/6 inhibitors plus endocrine therapy improve overall survival in advanced HR+/HER2-breast cancer: A meta-analysis of randomized controlled trials. Breast J. 2020;26(7):1439-1443. https://doi.org/10.1111/tbj.13703.Wang L., Gao S., Li D., Ran X., Sheng Z., Wu W., Yang X. CDK4/6 inhibitors plus endocrine therapy improve overall survival in advanced HR+/HER2-breast cancer: A meta-analysis of randomized controlled trials. Breast J. 2020;26(7):1439-1443. https://doi.org/10.1111/tbj.13703.Slamon D.j., Neven P., Chia S., jerusalem G., De Laurentiis M., Im S. et al. Ribociclib plus fulvestrant for postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in the phase III randomized MONALEESA-3 trial: updated overall survival. Ann Oncol. 2021;32(8):1015-1024. https://doi.org/10.1016/j.annonc.2021.05.353.Slamon D.j., Neven P., Chia S., jerusalem G., De Laurentiis M., Im S. et al. Ribociclib plus fulvestrant for postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in the phase III randomized MONALEESA-3 trial: updated overall survival. Ann Oncol. 2021;32(8):1015-1024. https://doi.org/10.1016/j.annonc.2021.05.353.Neven P., Petrakova K., Val Bianchi G., De la Cruz-Merino j., jerusalem G., Sonke G.S. et al. Biomarker analysis by baseline circulating tumor DNA alterations in the MONALEESA-3 study. Cancer Res. 2019;79(4 Suppl.):PD2-05. https://doi.org/10.1158/1538-7445.SABCS18-PD2-05.Neven P., Petrakova K., Val Bianchi G., De la Cruz-Merino j., jerusalem G., Sonke G.S. et al. Biomarker analysis by baseline circulating tumor DNA alterations in the MONALEESA-3 study. Cancer Res. 2019;79(4 Suppl.):PD2-05. https://doi.org/10.1158/1538-7445.SABCS18-PD2-05.Sobhani N., Roviello G., Corona S.P., Scaltriti M., Ianza A., Bortul M. et al. The Prognostic Value of PI3K Mutational Status in Breast Cancer: A Meta-analysis. J Cell Biochem. 2018;119(6):4287-4292. https://doi.org/10.1002/jcb.26687.Sobhani N., Roviello G., Corona S.P., Scaltriti M., Ianza A., Bortul M. et al. The Prognostic Value of PI3K Mutational Status in Breast Cancer: A Meta-analysis. J Cell Biochem. 2018;119(6):4287-4292. https://doi.org/10.1002/jcb.26687.Andre F., Ciruelos E., Rubovszky G., Campone M., Loibl S., Rugo H.S. et al. Alpelisib for PIK3CA-Mutated, Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2019;380(20):1929-1940. https://doi.org/10.1016/j.annonc.2020.10.596.Andre F., Ciruelos E., Rubovszky G., Campone M., Loibl S., Rugo H.S. et al. Alpelisib for PIK3CA-Mutated, Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2019;380(20):1929-1940. https://doi.org/10.1016/j.annonc.2020.10.596.Andre F., Ciruelos E.M., juric D., Loibl S., Campone M., Mayer I.A. et al. Alpelisib plus fulvestrant for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: final overall survival results from SOLAR-1. Ann Oncol. 2021;32(2):208-217. https://doi.org/10.1016/j.annonc.2020.11.011.Andre F., Ciruelos E.M., juric D., Loibl S., Campone M., Mayer I.A. et al. Alpelisib plus fulvestrant for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: final overall survival results from SOLAR-1. Ann Oncol. 2021;32(2):208-217. https://doi.org/10.1016/j.annonc.2020.11.011.Rugo H.S., Andre F., Yamashita T., Cerda H., Toledano I., Stemmer S.M. et al. Time course and management of key adverse events during the randomized phase III SOLAR-1 study of PI3K inhibitor alpelisib plus fulvestrant in patients with HR-positive advanced breast cancer. Ann Oncol. 2020;31(8):1001-1010. https://doi.org/10.1016/j.nnonc.2020.05.001.Rugo H.S., Andre F., Yamashita T., Cerda H., Toledano I., Stemmer S.M. et al. Time course and management of key adverse events during the randomized phase III SOLAR-1 study of PI3K inhibitor alpelisib plus fulvestrant in patients with HR-positive advanced breast cancer. Ann Oncol. 2020;31(8):1001-1010. https://doi.org/10.1016/j.nnonc.2020.05.001.Bartsch R. ASCO 2020: highlights in breast cancer. Memo. 2021;14(1): 58-61. https://doi.org/10.1007/s12254-021-00674-9.Bartsch R. ASCO 2020: highlights in breast cancer. Memo. 2021;14(1): 58-61. https://doi.org/10.1007/s12254-021-00674-9.Rugo H.S., Lerebours F., Ciruelos E.M., Drullinsky P., Borrego M.R., Neven P. et al. Alpelisib (ALP) + fulvestrant (FUL) in patients (pts) with PIK3CA-mutated (mut) hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) previously treated with cyclin-dependent kinase 4/6 inhibitor (CDKi) + aromatase inhibitor (AI): BYLieve study results. J Clin Oncol. 2020;38(15_ suppl):1006-1006. https://doi.org/10.1200/JCO.2020.38.15_suppl.1006.Rugo H.S., Lerebours F., Ciruelos E.M., Drullinsky P., Borrego M.R., Neven P. et al. Alpelisib (ALP) + fulvestrant (FUL) in patients (pts) with PIK3CA-mutated (mut) hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) previously treated with cyclin-dependent kinase 4/6 inhibitor (CDKi) + aromatase inhibitor (AI): BYLieve study results. J Clin Oncol. 2020;38(15_ suppl):1006-1006. https://doi.org/10.1200/JCO.2020.38.15_suppl.1006.Rugo H.S., Lerebours F., Juric D., Turner N., Chia S., Drullinsky P. et al. Alpelisib + letrozole in patients with PIK3CA-mutated, hormone-receptor positive (HR+), human epidermal growth factor receptor-2negative (HER2-) advanced breast cancer (ABC) previously treated with a cyclindependent kinase 4/6 inhibitor (CDK4/6i) + fulvestrant: BYLieve study results. Cancer Res. 2021;81(4_Suppl.):PD2-07. https://doi.org/10.1158/1538-7445.SABCS20-PD2-07.Rugo H.S., Lerebours F., Juric D., Turner N., Chia S., Drullinsky P. et al. Alpelisib + letrozole in patients with PIK3CA-mutated, hormone-receptor positive (HR+), human epidermal growth factor receptor-2negative (HER2-) advanced breast cancer (ABC) previously treated with a cyclindependent kinase 4/6 inhibitor (CDK4/6i) + fulvestrant: BYLieve study results. Cancer Res. 2021;81(4_Suppl.):PD2-07. https://doi.org/10.1158/1538-7445.SABCS20-PD2-07.Rugo H.S., Neven P., Saffie I., Park Y.H., Laurentiis M., Lerebours F. et al. Alpelisib + fulvestrant in patients with PIK3CA-mutated, HR+, HER2— advanced breast cancer (ABC) who received chemotherapy or endocrine therapy (ET) as immediate prior treatment: BYLieve Cohort C primary results and exploratory biomarker analyses. Cancer Res. 2022;82(4_Suppl.):PD3-05. https://doi.org/10.1158/1538-7445.SABCS21-PD13-05.Rugo H.S., Neven P., Saffie I., Park Y.H., Laurentiis M., Lerebours F. et al. Alpelisib + fulvestrant in patients with PIK3CA-mutated, HR+, HER2— advanced breast cancer (ABC) who received chemotherapy or endocrine therapy (ET) as immediate prior treatment: BYLieve Cohort C primary results and exploratory biomarker analyses. Cancer Res. 2022;82(4_Suppl.):PD3-05. https://doi.org/10.1158/1538-7445.SABCS21-PD13-05.Juric D., Turner N., Prat A., Chia S., Ciruelos E.M., Ruiz-Borrego M. et al. Alpelisib + endocrine therapy (ET) in patients with hormone receptorpositive (HR+), human epidermal growth factor receptor 2-negative (HER2-), PIK3CA-mutated advanced breast cancer (ABC) previously treated with cyclindependent kinase 4/6 inhibitor (CDK4/6i): Biomarker analyses from the Phase II BYLieve study. Cancer Res. 2022;82(4_Suppl.):P5-13-03. https://doi.org/10.1158/1538-7445.SABCS21-P5-13-03.Juric D., Turner N., Prat A., Chia S., Ciruelos E.M., Ruiz-Borrego M. et al. Alpelisib + endocrine therapy (ET) in patients with hormone receptorpositive (HR+), human epidermal growth factor receptor 2-negative (HER2-), PIK3CA-mutated advanced breast cancer (ABC) previously treated with cyclindependent kinase 4/6 inhibitor (CDK4/6i): Biomarker analyses from the Phase II BYLieve study. Cancer Res. 2022;82(4_Suppl.):P5-13-03. https://doi.org/10.1158/1538-7445.SABCS21-P5-13-03.Chia S., Ciruelos E.M., Rugo H.S., Lerebours F., Ruiz-Borrego M., Drullinsky P. et al. Effect of duration of prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) therapy (≤6 mo or >6 mo) on alpelisib benefit in patients with hormone receptorpositive (HR+), human epidermal growth factor receptor 2-negative (HER2-), PIK3CA-mutated advanced breast cancer (ABC) from BYLieve. Cancer Res. 2022;82(4_Suppl.):P1-18-08. https://doi.org/10.1158/1538-7445.SABCS21-P1-18-08.Chia S., Ciruelos E.M., Rugo H.S., Lerebours F., Ruiz-Borrego M., Drullinsky P. et al. Effect of duration of prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) therapy (≤6 mo or >6 mo) on alpelisib benefit in patients with hormone receptorpositive (HR+), human epidermal growth factor receptor 2-negative (HER2-), PIK3CA-mutated advanced breast cancer (ABC) from BYLieve. Cancer Res. 2022;82(4_Suppl.):P1-18-08. https://doi.org/10.1158/1538-7445.SABCS21-P1-18-08.Turner S., Chia S., Kanakamedala H., Hsu W.-C., Park J., Chandiwana D. et al. Effectiveness of Alpelisib + Fulvestrant Compared with Real-World Standard Treatment Among Patients with HR+, HER2-, PIK3CA-Mutated Breast Cancer. Oncologist. 2021;26(7):e1133-e1142. https://doi.org/10.1002/onco.13804.Turner S., Chia S., Kanakamedala H., Hsu W.-C., Park J., Chandiwana D. et al. Effectiveness of Alpelisib + Fulvestrant Compared with Real-World Standard Treatment Among Patients with HR+, HER2-, PIK3CA-Mutated Breast Cancer. Oncologist. 2021;26(7):e1133-e1142. https://doi.org/10.1002/onco.13804.Коваленко Е.И., Артамонова Е.В. Алпелисиб как новая возможность лечения пациентов с мутацией PIK3CA. Эффективность и переносимость терапии на примере клинического случая. Медицинский совет. 2021;(S4):103-107. https://doi.org/10.21518/2079-701X-2021-4S-103-107.Kovalenko E.I., Artamonova E.V Alpelisib as a new treatment option for patients with the PIK3CA mutation. The effectiveness and tolerability of therapy on the example of a clinical case. Meditsinskiy Sovet. 2021;(4S): 103-107. (In Russ.) https://doi.org/10.21518/2079-701X-2021-4S-103-107.Филоненко Д.А., Ибрагимова Т.М., Польшина Н.И., Белогурова А.В., Хатькова Е.И., Арутюнян Э.А. и др. Таргетная терапия люминального HER2-негативного метастатического рака молочной железы c мутацией PIK3CA: комбинация алпелисиба с фулвестрантом в реальной клинической практике. Медицинский совет. 2021;(20):75-82. https://doi.org/10.21518/2079-701X-2021-20-75-82.Filonenko D.A., Ibragimova T.M., Polshina N.I., Belogurova A.V., Khatkova E.I., Arutiunian E.A. et al. Target therapy of luminal HER2-negative advanced breast cancer with PIK3CA mutation: combination of alpelisib plus fulves-trant in real clinical practice. Meditsinskiy Sovet. 2021;(20):75-82. (In Russ.) https://doi.org/10.21518/2079-701X-2021-20-75-82.Kennecke H., Yerushalmi R., Woods R., Cheang M.C.U., Voduc D., Speers C.H. et al. Metastatic behavior of breast cancer subtypes. J Clin Oncol. 2010;28(20):3271-3277. https://doi.org/10.1200/JCO.2009.25.9820.Kennecke H., Yerushalmi R., Woods R., Cheang M.C.U., Voduc D., Speers C.H. et al. Metastatic behavior of breast cancer subtypes. J Clin Oncol. 2010;28(20):3271-3277. https://doi.org/10.1200/JCO.2009.25.9820.Ji L., Cheng L., Zhu X., Gao Y., Fan L., Wang Z. Risk and prognostic factors of breast cancer with liver metastases. BMC Cancer. 2021;21(1):238. https://doi.org/10.1186/s12885-021-07968-5.Ji L., Cheng L., Zhu X., Gao Y., Fan L., Wang Z. Risk and prognostic factors of breast cancer with liver metastases. BMC Cancer. 2021;21(1):238. https://doi.org/10.1186/s12885-021-07968-5.Yardley D.A., Nusch A., Yap Y.S., Sonke G.S., Bachelot Th., Chan A. et al. Overall survival (OS) in patients (pts) with advanced breast cancer (ABC) with visceral metastases (mets), including those with liver mets, treated with ribociclib (RIB) plus endocrine therapy (ET) in the MONALEESA (ML) -3 and -7 trials. J Clin Oncol. 2020;38(15_suppl):1054-1054. https://doi.org/10.1200/JCO.2020.38.15_suppl.1054.Yardley D.A., Nusch A., Yap Y.S., Sonke G.S., Bachelot Th., Chan A. et al. Overall survival (OS) in patients (pts) with advanced breast cancer (ABC) with visceral metastases (mets), including those with liver mets, treated with ribociclib (RIB) plus endocrine therapy (ET) in the MONALEESA (ML) -3 and -7 trials. J Clin Oncol. 2020;38(15_suppl):1054-1054. https://doi.org/10.1200/JCO.2020.38.15_suppl.1054.Мазурина Н.В., Артамонова Е.В., Белоярцева М.Ф., Волкова Е.И., Ганьшина И.П., Трошина Е.А. и др. Консенсус по профилактике и коррекции гипергликемии у пациентов, получающих терапию препаратом алпелисиб. Современная онкология. 2020;22(4):56-59. https://doi.org/10.26442/18151434.2020.4.200566.Mazurina N.V., Artamonova E.V., Beloyartseva M.F., Volkova E.I., Ganshina I.P., Troshina E.A. et al. The consensus on the prevention and correction of hyperglycemia in patients with HR+ HER2- metastatic breast cancer treated with alpelisib. Journal of Modern Oncology. 2020;22(4):56-59. (In Russ.) https://doi.org/10.26442/18151434.2020.4.200566.Blow T., Hyde P.N., Falcone J.N., Neinstein A., Vasan N., Chitkara R. et al. Treating Alpelisib-Induced Hyperglycemia with Very Low Carbohydrate Diets and Sodium-Glucose Co-Transporter 2 Inhibitors: A Case Series. Integr Cancer Ther. 2021;20:15347354211032283. https://doi.org/10.1177/15347354211032283.Blow T., Hyde P.N., Falcone J.N., Neinstein A., Vasan N., Chitkara R. et al. Treating Alpelisib-Induced Hyperglycemia with Very Low Carbohydrate Diets and Sodium-Glucose Co-Transporter 2 Inhibitors: A Case Series. Integr Cancer Ther. 2021;20:15347354211032283. https://doi.org/10.1177/15347354211032283.Rugo H.S., Andre F., Yamashita T., Cerda H., Toledano I., Stemmer S.M. et al. Time course and management of key adverse events during the randomized phase III SOLAR-1 study of PI3K inhibitor alpelisib plus fulvestrant in patients with HR-positive advanced breast cancer. Ann Oncol. 2020;31(8):1001-1010. https://doi.org/10.1016/j.annonc.2020.05.001.Rugo H.S., Andre F., Yamashita T., Cerda H., Toledano I., Stemmer S.M. et al. Time course and management of key adverse events during the randomized phase III SOLAR-1 study of PI3K inhibitor alpelisib plus fulvestrant in patients with HR-positive advanced breast cancer. Ann Oncol. 2020;31(8):1001-1010. https://doi.org/10.1016/j.annonc.2020.05.001.Gennari A., Andre F., Barrios C.H., Gennari A., Andre F., Barrios C.H. et al. ESMO Clinical Practice Guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer. Ann Oncol. 2021;32(12): 1475-1495. https://doi.org/10.1016/j.annonc.2021.09.019.Gennari A., Andre F., Barrios C.H., Gennari A., Andre F., Barrios C.H. et al. ESMO Clinical Practice Guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer. Ann Oncol. 2021;32(12): 1475-1495. https://doi.org/10.1016/j.annonc.2021.09.019.Шливко И.Л., Гаранина О.Е., Артамонова Е.В., Ганьшина И.П., Жукова Л.Г., Королева И.А. и др. Консенсус по профилактике и коррекции сыпи у пациентов, получающих терапию препаратом алпелисиб. Современная онкология. 2021;23(4):572-576. https://doi.org/10.26442/18151434.2021.4.201275.Shlivko I.L., Garanina O.E., Artamonova E.V., Ganshina I.P., Zhukova L.G., Koroleva I.A. et al. The consensus on the prevention and correction of rash in patients with HR+ HER2- metastatic breast cancer treated with alpelisib. Journal of Modern Oncology. 2021;23(4):572-576. (In Russ.) https://doi.org/10.26442/18151434.2021.4.201275.Jensen J.D., Laenkholm A.-V., Knoop A., Ewertz M., Bandaru R., Liu W. et al. PIK3CA mutations may be discordant between primary and corresponding metastatic disease in breast cancer. Clin Cancer Res. 2011;17(4):667-677. https://doi.org/10.1158/1078-0432.CCR-10-1133.Jensen J.D., Laenkholm A.-V., Knoop A., Ewertz M., Bandaru R., Liu W. et al. PIK3CA mutations may be discordant between primary and corresponding metastatic disease in breast cancer. Clin Cancer Res. 2011;17(4):667-677. https://doi.org/10.1158/1078-0432.CCR-10-1133.

The authors declare that there are no conflicts of interest present.