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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="research-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Russian Journal of Biotherapy</journal-id><journal-title-group><journal-title xml:lang="en">Russian Journal of Biotherapy</journal-title><trans-title-group xml:lang="ru"><trans-title>Российский биотерапевтический журнал</trans-title></trans-title-group></journal-title-group><issn publication-format="print">1726-9784</issn><issn publication-format="electronic">1726-9792</issn><publisher><publisher-name xml:lang="en">Publishing House ABV Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">1580</article-id><article-id pub-id-type="doi">10.17650/1726-9784-2025-24-4-19-30</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>ORIGINAL REPORTS</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>ОРИГИНАЛЬНЫЕ СТАТЬИ</subject></subj-group><subj-group subj-group-type="article-type"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Leptomeningeal breast cancer metastases: clinical and cytological features on the background of intrathecal methotrexate therapy</article-title><trans-title-group xml:lang="ru"><trans-title>Лептоменингеальные метастазы рака молочной железы: клинико-цитологические особенности на фоне интратекальной терапии метотрексатом</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-1766-0032</contrib-id><name-alternatives><name xml:lang="en"><surname>Belov</surname><given-names>Dmitry M.</given-names></name><name xml:lang="ru"><surname>Белов</surname><given-names>Д. М.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>dmbelov@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4160-9598</contrib-id><name-alternatives><name xml:lang="en"><surname>Bekyashev</surname><given-names>Ali K.</given-names></name><name xml:lang="ru"><surname>Бекяшев</surname><given-names>А. Х.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>dmbelov@mail.ru</email><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-5242-9309</contrib-id><name-alternatives><name xml:lang="en"><surname>Moskvina</surname><given-names>Ekaterina A.</given-names></name><name xml:lang="ru"><surname>Москвина</surname><given-names>Е. А.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>dmbelov@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4218-9652</contrib-id><name-alternatives><name xml:lang="en"><surname>Naskhletashvili</surname><given-names>David R.</given-names></name><name xml:lang="ru"><surname>Насхлеташвили</surname><given-names>Д. Р.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>dmbelov@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1854-3455</contrib-id><name-alternatives><name xml:lang="en"><surname>Borunova</surname><given-names>Anna A.</given-names></name><name xml:lang="ru"><surname>Борунова</surname><given-names>А. А.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>dmbelov@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-1389-9038</contrib-id><name-alternatives><name xml:lang="en"><surname>Alyoshin</surname><given-names>Vladimir A.</given-names></name><name xml:lang="ru"><surname>Алешин</surname><given-names>В. А.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>dmbelov@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4125-7342</contrib-id><name-alternatives><name xml:lang="en"><surname>Mitrofanov</surname><given-names>Alexey A.</given-names></name><name xml:lang="ru"><surname>Митрофанов</surname><given-names>А. А.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>dmbelov@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-8880-1758</contrib-id><name-alternatives><name xml:lang="en"><surname>Prozorenko</surname><given-names>Evgeny V.</given-names></name><name xml:lang="ru"><surname>Прозоренко</surname><given-names>Е. В.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>dmbelov@mail.ru</email><xref ref-type="aff" rid="aff3"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0002-7517-4358</contrib-id><name-alternatives><name xml:lang="en"><surname>Khatukayeva</surname><given-names>Madina M.</given-names></name><name xml:lang="ru"><surname>Хатукаева</surname><given-names>М. М.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>dmbelov@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-4031-0540</contrib-id><name-alternatives><name xml:lang="en"><surname>Sufianov</surname><given-names>Rinat A.</given-names></name><name xml:lang="ru"><surname>Суфианов</surname><given-names>Р. А.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>dmbelov@mail.ru</email><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff3"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-7631-5699</contrib-id><name-alternatives><name xml:lang="en"><surname>Zabotina</surname><given-names>Tatiana N.</given-names></name><name xml:lang="ru"><surname>Заботина</surname><given-names>Т. Н.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>dmbelov@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia</institution></aff><aff><institution xml:lang="ru">ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н. Н. Блохина» Минздрава России</institution></aff></aff-alternatives><aff-alternatives id="aff2"><aff><institution xml:lang="en">Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia</institution></aff><aff><institution xml:lang="ru">ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России</institution></aff></aff-alternatives><aff-alternatives id="aff3"><aff><institution xml:lang="en">I.M. Sechenov First Moscow State Medical University (Sechenovskiy University), Ministry of Health of Russia</institution></aff><aff><institution xml:lang="ru">ФГАОУ ВО «Первый Московский государственный медицинский университет им. И. М. Сеченова» Минздрава России (Сеченовский Университет)</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2025-12-17" publication-format="electronic"><day>17</day><month>12</month><year>2025</year></pub-date><volume>24</volume><issue>4</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>19</fpage><lpage>30</lpage><history><date date-type="received" iso-8601-date="2025-10-15"><day>15</day><month>10</month><year>2025</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2025, Belov D.M., Bekyashev A.K., Moskvina E.A., Naskhletashvili D.R., Borunova A.A., Alyoshin V.A., Mitrofanov A.A., Prozorenko E.V., Khatukayeva M.M., Sufianov R.A., Zabotina T.N.</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2025, Белов Д.М., Бекяшев А.Х., Москвина Е.А., Насхлеташвили Д.Р., Борунова А.А., Алешин В.А., Митрофанов А.А., Прозоренко Е.В., Хатукаева М.М., Суфианов Р.А., Заботина Т.Н.</copyright-statement><copyright-year>2025</copyright-year><copyright-holder xml:lang="en">Belov D.M., Bekyashev A.K., Moskvina E.A., Naskhletashvili D.R., Borunova A.A., Alyoshin V.A., Mitrofanov A.A., Prozorenko E.V., Khatukayeva M.M., Sufianov R.A., Zabotina T.N.</copyright-holder><copyright-holder xml:lang="ru">Белов Д.М., Бекяшев А.Х., Москвина Е.А., Насхлеташвили Д.Р., Борунова А.А., Алешин В.А., Митрофанов А.А., Прозоренко Е.В., Хатукаева М.М., Суфианов Р.А., Заботина Т.Н.</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://bioterapevt.abvpress.ru/jour/article/view/1580">https://bioterapevt.abvpress.ru/jour/article/view/1580</self-uri><abstract xml:lang="en"><p><bold>Background.</bold> Cytological examination of cerebrospinal fluid (CSF) and the dynamics of neurological symptoms are key in the diagnosis and evaluation of treatment effectiveness for leptomeningeal metastases. Quantitative assessment of circulating tumor cells in CSF is not routinely used. This study examined the correlation between the dynamics of tumor cell counts in CSF and the dynamics of neurological symptoms in patients with leptomeningeal metastases from breast cancer during intrathecal methotrexate therapy.</p> <p><bold>Aim.</bold> To identify clinical and cytological features in patients with leptomeningeal metastases from breast cancer during intrathecal methotrexate therapy.</p> <p><bold>Materials and methods.</bold> A retrospective analysis of 30 patients with leptomeningeal metastases from breast cancer who received intrathecal methotrexate in the Department of Neurooncology of the N. N. Blokhin National Medical Research Center of Oncology from 2018 to 2024.</p> <p><bold>Results.</bold> All 30 cases involved women with ductal or lobular breast cancer. The highest proportion of patients with leptomeningeal metastases were found in stage III–C breast cancer (33.3 %). Cytological analysis of cerebrospinal fluid and neurological status assessment were performed before each methotrexate administration. The correlation was monitored throughout the treatment period. A direct statistically significant relationship has been found between the number of tumor cells in cerebrospinal fluid and the severity of neurological disorders: at one month after treatment start <italic>r</italic> = 0.702; <italic>p</italic> = 0.000 and at two months <italic>r</italic> = 0.819; <italic>p</italic> = 0.000. However, prior to therapy initiation there was no correlation between these parameters (<italic>r</italic> = 0.056; <italic>p</italic> = 0.770). Thus, with a low level of tumor cytosis pronounced neurological symptoms could be present (75 cells, symptom score – 6 points), while conversely, with an elevated cytosis level mild neurological manifestations might occur (400 cells, symptom score – 3 points). It was found that only with a decrease in the number of tumor cells in the cerebrospinal fluid by 2 or more times (or by 50 %) does the severity of neurological disorders change. And an increase in the severity of neurological disorders occurs in the case of an increase in the number of cells in the cerebrospinal fluid by 1.2 times (or by 20 %). Moreover, this correlation was maintained throughout the treatment.</p> <p><bold>Conclusion.</bold> Evaluation of the dynamics of tumor cytosis in the cerebrospinal fluid, along with clinical characteristics, can be recommended for use in predicting the response to treatment in patients with leptomeningeal metastases of breast cancer.</p></abstract><trans-abstract xml:lang="ru"><p><bold>Введение.</bold> Цитологическое исследование ликвора и динамика неврологической симптоматики являются ведущими в диагностике и оценке эффективности лечения при лептоменингеальном метастазировании. Количественная оценка циркулирующих опухолевых клеток в ликворе не используются в рутинной практике. В работе прослежена корреляция динамики количества опухолевых клеток в ликворе с динамикой неврологической симптоматики у пациенток с лептоменингеальными метастазами рака молочной железы (РМЖ) в период проведения интратекальной терапии метотрексатом.</p> <p><bold>Цель исследования</bold> – выявить клинико-цитологические особенности у пациенток с лептоменингеальными метастазами РМЖ в процессе интратекальной терапии метотрексатом.</p> <p><bold>Материалы и методы.</bold> Ретроспективный анализ 30 пациенток с лептоменингеальными метастазами РМЖ, получавших интратекальное введение метотрексата в отделении нейроонкологии НМИЦ онкологии им. Н. Н. Блохина с 2018 по 2024 г.</p> <p><bold>Результаты.</bold> Во всех 30 случаях РМЖ был протокового или долькового типа. Наибольшее число пациенток с лептоменингеальными метастазами встречалось при IIIС-стадии РМЖ (10/30; 33,3 %). Цитологический анализ ликвора и оценку неврологического статуса проводили перед каждым введением метотрексата. Корреляция была прослежена на всем протяжении лечения. Выявлена прямая статистически значимая зависимость количества опухолевых клеток в ликворе и степени выраженности неврологических нарушений: через 1 мес от начала лечения <italic>r</italic> = 0,702; <italic>p</italic> = 0,000 и через 2 мес – <italic>r</italic> = 0,819; <italic>p</italic> = 0,000. Однако до начала терапии зависимость между этими показателями отсутствовала (<italic>r</italic> = 0,056; <italic>p</italic> = 0,770). Так, при невысоком уровне опухолевого цитоза могла быть выраженная неврологическая симптоматика (75 клеток, симптоматика – 6 баллов) и, наоборот, при повышенном уровне цитоза могли быть легкие неврологические проявления (400 клеток, симптоматика – 3 балла). Обнаружено, что только при уменьшении количества опухолевых клеток в ликворе в 2 раза и более меняется степень выраженности неврологических нарушений. Увеличение выраженности неврологических нарушений происходит в случае повышения количества клеток в ликворе в 1,2 раза. Причем такая корреляция сохранялась на всем протяжении лечения.</p> <p><bold>Заключение.</bold> Оценка динамики опухолевого цитоза в ликворе наряду с клинической характеристикой могут быть рекомендованы к использованию в прогнозе ответа на лечение у пациенток с лептоменингеальными метастазами РМЖ.</p></trans-abstract><kwd-group xml:lang="en"><kwd>breast cancer</kwd><kwd>leptomeningeal metastas</kwd><kwd>intrathecal chemotherapy</kwd><kwd>cerebrospinal fluid cytological diagnostics</kwd><kwd>clinical-cytological correlation</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>рак молочной железы</kwd><kwd>лептоменингеальный метастаз</kwd><kwd>интратекальная химиотерапия</kwd><kwd>цитологическая диагностика ликвора</kwd><kwd>клинико-цитологическая корреляция</kwd></kwd-group><funding-group><award-group><funding-source><institution-wrap><institution xml:lang="ru">Министерство здравоохранения Российской Федерации</institution></institution-wrap><institution-wrap><institution xml:lang="en">Ministry of Health of the Russian Federation</institution></institution-wrap></funding-source><award-id>056-00065-23 ПР</award-id></award-group></funding-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Le Rhun E., Weller M. 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