medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2019-10-129-134medsovet-3063Research ArticleКЛИНИЧЕСКОЕ НАБЛЮДЕНИЕCLINICAL OBSERVATIONСистемный контроль церебральных метастазов у больной метастатическим HER2-положительным раком молочной железы. Клинический случайSystemic control of cerebral metastases in a patient with HER2-positive metastatic breast cancer. Clinical caseМеньшиковаC. Ф.MenshikovaS. F.

клинический ординатор кафедры онкологии Федераль ного государственного автономного образовательного учреждения высшего образования «Первый Московский государственный медицинский университет имени И.М. Сеченова» Министерства здравоохранения Российской Федерации (Сеченовский Университет).

Resident Medical Practitioner, Chair for Oncology, Federal State Autonomous Educational Institution for Higher Education «Sechenov First Moscow State Medical University» of the Ministry of Heath of the Russian Federation (Sechenov University).

sophie.menshikova@gmail.comФроловаМ. А.FrolovaM. A.

к.м.н., научный сотрудник отделения клинической фармакологии и химиотерапии Федерального государственного бюджетного учреждения «Национальный медицинский исследовательский центр онкологии имени Н.Н. Блохина» Министерства здравоохранения Российской Федерации.

Cand. of Sci. (Med.), Researcher, Department of Clinical Pharmacology and Chemotherapy, Federal State Budgetary Institution «Blokhin Russian Cancer Research Center» of the Ministry of Health of the Russian Federation.

drfrolova@yandex.ruСтенинаМ. Б.SteninaM. B.

д.м.н., ведущий научный сотрудник отделения клинической фармакологии и химиотерапии Федерального государственного бюджетного учреждения «Национальный медицинский исследовательский центр онкологии имени Н.Н. Блохина» Министерства здравоохранения Российской Федерации.

Dr. of Sci. (Med.), Lead Researcher, Department of Clinical Pharmacology and Chemotherapy, Federal State Budgetary Institution «Blokhin Russian Cancer Research Center» of the Ministry of Health of the Russian Federation.

mstenina@mail.ruФедеральное государственное автономное образовательное учреждение высшего образования «Первый Московский государственный медицинский университет имени И.М. Сеченова» Министерства здравоохранения Российской Федерации (Сеченовский Университет).РоссияFederal State Autonomous Educational Institution of Higher Education First Moscow State Medical University named after I.M. Sechenov of the Ministry of Health of the Russian Federation (Sechenov University).Russian FederationФедеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр онкологии имени Н.Н. Блохина» Министерства здравоохранения Российской Федерации.РоссияFederal State Budgetary Institution «Blokhin Russian Cancer Research Center» of the Ministry of Health of the Russian Federation.Russian Federation201923062019010129134Copyright © Меньшикова C.Ф., Фролова М.А., Стенина М.Б., 20192019Меньшикова C.Ф., Фролова М.А., Стенина М.Б.Menshikova S.F., Frolova M.A., Stenina M.B.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/3063

Симптомное поражение центральной нервной системы (ЦНС) диагностируют у 10–16% больных метастатическим раком молочной железы (РМЖ). Половина всех случаев приходится на долю HER2-положительных подтипов. В настоящее время отсутствуют общепринятые алгоритмы в отношении сочетания и последовательности локального и системного лечения у данной категории больных. Согласно существующим рекомендациям, основным методом лечения метастатического поражения головного мозга является локальная терапия в различных вариантах. При исчерпании возможностей локального лечения больные HER2-положительным РМЖ с метастатическим поражением ЦНС могут получать анти-HER2-терапию в сочетании с химио- или гормональной терапией (при люминальных опухолях) или в самостоятельном виде. Трастузумаб плохо проникает сквозь гематоэнцефалический барьер, но режимы лечения с включением трастузумаба увеличивают продолжительность жизни у больных HER2-положительным РМЖ с метастазами в ЦНС, в основном за счет контроля экстракраниальных очагов. Лапатиниб, напротив, хорошо проникает через гематоэнцефалический барьер, а его комбинация с капецитабином позволяет добиться ответов у интенсивно предлеченных больных, особенно в случаях, когда единственным местом прогрессирования болезни является ЦНС.

Symptomatic central nervous system (CNS) metastases are diagnosed in 10–16% of patients with metastatic breast cancer (BC). Half of all these cases are HER2-positive. At present, there are no generally accepted algorithms regarding the combination and sequence of local and systemic treatment options for these patients. According to current guidelines, different local management options remain one of the main treatment methods of brain metastases control. When local treatment is limited, patients with HER2-positive BC with СNS metastases can receive anti-HER2 therapy in combination with chemo- or hormonal therapy (for luminal tumors) or as single option. Trastuzumab poorly penetrates the blood-brain barrier, but trastuzumab-based treatment schedules increase the life expectancy in patients with HER2-positive BC with CNS metastases mainly due to control of extracranial metastases. Lapatinib, by contrast, penetrates the blood-brain barrier well, and its combination with capecitabine achieves response in heavily pretreated patients, especially in those who have central nervous system metastases as the only site of disease progression.

рак молочной железытрастузумабкапецитабинлапатинибметастазы в головной мозгbreast cancertrastuzumabcapecitabinelapatinibbrain metastasesReferencesBarnholtz-Sloan J.S., Sloan A.E., Davis F.G., Vigneau F.D., Lai P., Sawaya R.E. Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol. 2004;22:2865-72.Barnholtz-Sloan J.S., Sloan A.E., Davis F.G., Vigneau F.D., Lai P., Sawaya R.E. Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol. 2004;22:2865-72.Tsukada Y., Fouad A., Pickren J.W., Lane W.W. Central nervous system metastasis from breast carcinoma. Autopsy study. Cancer. 1983;52:2349-54.Tsukada Y., Fouad A., Pickren J.W., Lane W.W. Central nervous system metastasis from breast carcinoma. Autopsy study. Cancer. 1983;52:2349-54.Evans A.J., James J.J., Cornford E.J., Chan S.Y., Burrell H.C., Pinder S.E. et al. Brain metastases from breast cancer: identification of a high-risk group. Clin Oncol (R Coll Radiol). 2004;16:345-9.Evans A.J., James J.J., Cornford E.J., Chan S.Y., Burrell H.C., Pinder S.E. et al. Brain metastases from breast cancer: identification of a high-risk group. Clin Oncol (R Coll Radiol). 2004;16:345-9.Duchnowska R., Loibl S., Jassem J. Tyrosine kinase inhibitors for brain metastases in HER2- positive breast cancer. Cancer Treatment Reviews. 2018;67:71-77.Duchnowska R., Loibl S., Jassem J. Tyrosine kinase inhibitors for brain metastases in HER2- positive breast cancer. Cancer Treatment Reviews. 2018;67:71-77.Стенина М. Б., Жукова Л. Г., Королева И. А., Пароконная А. А., Семиглазова Т. Ю., Тюляндин С. А. и соавт. Практические рекомендации по лекарственному лечению инвазивного рака молочной железы. Злокачественные опухоли: Практические рекомендации RUSSCO #3s2. 2018;8:113–144. [Stenina M.B., Zhukova L.G., Koroleva I.A., Parokonnaya A. A., Semiglazova T. Yu., Tyulyandin S. A. et al. Practical recommendations for the treatment of invasive breast cancer. Zlokachestvennye opuholi: Prakticheskie rekomendacii RUSSCO #3s2. 2018;8:113–144.] (In Russ.)Стенина М. Б., Жукова Л. Г., Королева И. А., Пароконная А. А., Семиглазова Т. Ю., Тюляндин С. А. и соавт. Практические рекомендации по лекарственному лечению инвазивного рака молочной железы. Злокачественные опухоли: Практические рекомендации RUSSCO #3s2. 2018;8:113–144. [Stenina M.B., Zhukova L.G., Koroleva I.A., Parokonnaya A. A., Semiglazova T. Yu., Tyulyandin S. A. et al. Practical recommendations for the treatment of invasive breast cancer. Zlokachestvennye opuholi: Prakticheskie rekomendacii RUSSCO #3s2. 2018;8:113–144.] (In Russ.)Rohatgi N., Munshi A., Bajpai P. et al. Practical consensus recommendations on Her2 +ve breast cancer with solitary brain mets. South Asian J Cancer. 2018;7(2):118–122.Rohatgi N., Munshi A., Bajpai P. et al. Practical consensus recommendations on Her2 +ve breast cancer with solitary brain mets. South Asian J Cancer. 2018;7(2):118–122.Dijkers E.C., Oude Munnink T.H., Kosterink J.G., Brouwers A.H., Jager P.L., de Jong J.R. et al. Biodistribution of 89Zr-trastuzumab and PET imaging of HER2-positive lesions in patients with metastatic breast cancer. Clin Pharmacol Ther. 2010;87(5):586–92.Dijkers E.C., Oude Munnink T.H., Kosterink J.G., Brouwers A.H., Jager P.L., de Jong J.R. et al. Biodistribution of 89Zr-trastuzumab and PET imaging of HER2-positive lesions in patients with metastatic breast cancer. Clin Pharmacol Ther. 2010;87(5):586–92.Tamura K., Kurihara H., Yonemori K., Tsuda H., Suzuki J., Kono Y. et al. 64Cu-DOTAtrastuzumab PET imaging in patients with HER2-positive breast cancer. J Nucl Med. 2013;54(11):1869–75.Tamura K., Kurihara H., Yonemori K., Tsuda H., Suzuki J., Kono Y. et al. 64Cu-DOTAtrastuzumab PET imaging in patients with HER2-positive breast cancer. J Nucl Med. 2013;54(11):1869–75.Brufsky A.M., Mayer M., Rugo H.S., Kaufman P.A., Tan-Chiu E., Tripathy D. et al. Central nervous system metastases in patients with HER2- positive metastatic breast cancer: incidence, treatment, and survival in patients from registHER. Clin Cancer Res. 2011;17(14):4834–43.Brufsky A.M., Mayer M., Rugo H.S., Kaufman P.A., Tan-Chiu E., Tripathy D. et al. Central nervous system metastases in patients with HER2- positive metastatic breast cancer: incidence, treatment, and survival in patients from registHER. Clin Cancer Res. 2011;17(14):4834–43.Bartsch R., Rottenfusser A., Wenzel C., Dieckmann K., Pluschnig U., Altorjai G. et al. Trastuzumab prolongs overall survival in patients with brain metastases from Her2 positive breast cancer. J NeuroOncol. 2007;85(3):311–7.Bartsch R., Rottenfusser A., Wenzel C., Dieckmann K., Pluschnig U., Altorjai G. et al. Trastuzumab prolongs overall survival in patients with brain metastases from Her2 positive breast cancer. J NeuroOncol. 2007;85(3):311–7.Yap Y.S., Cornelio G.H., Devi B.C., Khorprasert C., Kim S.B., Kim T.Y. et al. Brain metastases in Asian HER2-positive breast cancer patients: anti-HER2 treatments and their impact on survival. Br J Cancer. 2012;107(7):1075–82.Yap Y.S., Cornelio G.H., Devi B.C., Khorprasert C., Kim S.B., Kim T.Y. et al. Brain metastases in Asian HER2-positive breast cancer patients: anti-HER2 treatments and their impact on survival. Br J Cancer. 2012;107(7):1075–82.Park B.B., Uhm J.E., Cho E.Y., Choi Y.L., Ji S.H., Nam D.H. et al. Prognostic factor analysis in patients with brain metastases from breast cancer: how can we improve the treatment outcomes? Cancer Chemother Pharmacol. 2009;63(4):627–33.Park B.B., Uhm J.E., Cho E.Y., Choi Y.L., Ji S.H., Nam D.H. et al. Prognostic factor analysis in patients with brain metastases from breast cancer: how can we improve the treatment outcomes? Cancer Chemother Pharmacol. 2009;63(4):627–33.Lin N.U., Carey L.A., Liu M.C., Younger J., Come S.E., Ewend M. et al. Phase II trial of lapatinib for brain metastases in patients with human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2008;26(12):1993–9.Lin N.U., Carey L.A., Liu M.C., Younger J., Come S.E., Ewend M. et al. Phase II trial of lapatinib for brain metastases in patients with human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2008;26(12):1993–9.Lin N.U., Dieras V., Paul D., Lossignol D., Christodoulou C., Stemmler H.J. et al. Multicenter phase II study of lapatinib in patients with brain metastases from HER2- positive breast cancer. Clin Cancer Res. 2009;15(4):1452–9.Lin N.U., Dieras V., Paul D., Lossignol D., Christodoulou C., Stemmler H.J. et al. Multicenter phase II study of lapatinib in patients with brain metastases from HER2- positive breast cancer. Clin Cancer Res. 2009;15(4):1452–9.Sutherland S., Ashley S., Miles D., Chan S., Wardley A., Davidson N. et al. Treatment of HER2-positive metastatic breast cancer with lapatinib and capecitabine in the lapatinib expanded access programme, including efficacy in brain metastases – the UK experience. Br J Cancer. 2010;102(6):995–1002.Sutherland S., Ashley S., Miles D., Chan S., Wardley A., Davidson N. et al. Treatment of HER2-positive metastatic breast cancer with lapatinib and capecitabine in the lapatinib expanded access programme, including efficacy in brain metastases – the UK experience. Br J Cancer. 2010;102(6):995–1002.Metro G., Foglietta J., Russillo M., Stocchi L., Vidiri A., Giannarelli D. et al. Clinical outcome of patients with brain metastases from HER2- positive breast cancer treated with lapatinib and capecitabine. Ann Oncol. 2011;22(3):625–30.Metro G., Foglietta J., Russillo M., Stocchi L., Vidiri A., Giannarelli D. et al. Clinical outcome of patients with brain metastases from HER2- positive breast cancer treated with lapatinib and capecitabine. Ann Oncol. 2011;22(3):625–30.Lin N.U., Eierman W., Greil R., Campone M., Kaufman B., Steplewski K. et al. Randomized phase II study of lapatinib plus capecitabine or lapatinib plus topotecan for patients with HER2-positive breast cancer brain metastases. J Neuro-Oncol. 2011;105(3):613–20.Lin N.U., Eierman W., Greil R., Campone M., Kaufman B., Steplewski K. et al. Randomized phase II study of lapatinib plus capecitabine or lapatinib plus topotecan for patients with HER2-positive breast cancer brain metastases. J Neuro-Oncol. 2011;105(3):613–20.Bachelot T., Romieu G., Campone M., Dieras V., Cropet C., Dalenc F. et al. Lapatinib plus capecitabine in patients with previously untreated brain metastases from HER2- positive metastatic breast cancer (LANDSCAPE): a single-group phase 2 study. Lancet Oncol. 2013;14(1):64–71.Bachelot T., Romieu G., Campone M., Dieras V., Cropet C., Dalenc F. et al. Lapatinib plus capecitabine in patients with previously untreated brain metastases from HER2- positive metastatic breast cancer (LANDSCAPE): a single-group phase 2 study. Lancet Oncol. 2013;14(1):64–71.Geyer C.E., Forster J., Lindquist D. et al. Lapatinib plus Capecitabine for HER2-Positive Advanced Breast Cancer. N Engl J Med. 2006;355:2733-2743.Geyer C.E., Forster J., Lindquist D. et al. Lapatinib plus Capecitabine for HER2-Positive Advanced Breast Cancer. N Engl J Med. 2006;355:2733-2743.Cameron D., Casey M., Press M., Lindquist D., Pienkowski T., Romieu C.G. et al. A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res Treat. 2008;112(3):533–43.Cameron D., Casey M., Press M., Lindquist D., Pienkowski T., Romieu C.G. et al. A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res Treat. 2008;112(3):533–43.Pivot X., Manikhas A., Zurawski B., Chmielowska E., Karaszewska B., Allerton R. et al. CEREBEL (EGF111438): a phase III, randomized, open-label study of lapatinib plus capecitabine versus trastuzumab plus capecitabine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2015;33(14):1564–73.Pivot X., Manikhas A., Zurawski B., Chmielowska E., Karaszewska B., Allerton R. et al. CEREBEL (EGF111438): a phase III, randomized, open-label study of lapatinib plus capecitabine versus trastuzumab plus capecitabine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2015;33(14):1564–73.Shawky H., Tawfik H. All-oral combination of lapatinib and capecitabine in patients with brain metastases from HER2-positive breast cancerea phase II study. J Egypt Natl Cancer Inst. 2014;26:187-94.Shawky H., Tawfik H. All-oral combination of lapatinib and capecitabine in patients with brain metastases from HER2-positive breast cancerea phase II study. J Egypt Natl Cancer Inst. 2014;26:187-94.Lin N.U., Freedman R.A., Ramakrishna N., Younger J., Storniolo A.M., Bellon J.R. et al. A phase I study of lapatinib with whole brain radiotherapy in patients with Human Epidermal Growth Factor Receptor 2 (HER2)- positive breast cancer brain metastases. Breast Cancer Res Treat. 2013;142:405-14.Lin N.U., Freedman R.A., Ramakrishna N., Younger J., Storniolo A.M., Bellon J.R. et al. A phase I study of lapatinib with whole brain radiotherapy in patients with Human Epidermal Growth Factor Receptor 2 (HER2)- positive breast cancer brain metastases. Breast Cancer Res Treat. 2013;142:405-14.Christodoulou C., Kalogera-Fountzila A., Karavasilis V., Kouvatseas G., Papandreou C.N. et al. Lapatinib with whole brain radiotherapy in patients with brain metastases from breast and non-small cell lung cancer: a phase II study of the Hellenic Cooperative Oncology Group (HeCOG). J Neurooncol. 2017;134:443-51.Christodoulou C., Kalogera-Fountzila A., Karavasilis V., Kouvatseas G., Papandreou C.N. et al. Lapatinib with whole brain radiotherapy in patients with brain metastases from breast and non-small cell lung cancer: a phase II study of the Hellenic Cooperative Oncology Group (HeCOG). J Neurooncol. 2017;134:443-51.

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