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<article article-type="research-article" dtd-version="1.3" 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" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">medalphabet</journal-id><journal-title-group><journal-title xml:lang="ru">Медицинский алфавит</journal-title><trans-title-group xml:lang="en"><trans-title>Medical alphabet</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2078-5631</issn><issn pub-type="epub">2949-2807</issn><publisher><publisher-name>ООО «Альфмед»</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.33667/2078-5631-2023-10-11-17</article-id><article-id custom-type="elpub" pub-id-type="custom">medalphabet-3154</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>Статьи</subject></subj-group></article-categories><title-group><article-title>Дозоуплотненная неоадъювантная химиотерапия первично-операбельного и местнораспространенного неоперабельного тройного-негативного рака молочной железы: первые результаты проспективного одноцентрового исследования</article-title><trans-title-group xml:lang="en"><trans-title>Dose-dense neoadjuvant chemotherapy of operable and locally advanced inoperable triple negative breast cancer: First results of single-centre prospective trial</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-4763-7992</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Коваленко</surname><given-names>Е. И.</given-names></name><name name-style="western" xml:lang="en"><surname>Kovalenko</surname><given-names>E. I.</given-names></name></name-alternatives><bio xml:lang="ru"><p> Коваленко Елена Игоревна, к. м. н., с. н. с. отделения химиотерапии № 11</p><p> Москва</p></bio><bio xml:lang="en"><p> Kovalenko Elena I., PhD Med, senior researcher at Dept of Chemotherapy No. 1</p><p> Moscow</p></bio><email xlink:type="simple">eikovalenko@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4108-439X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Жуликов</surname><given-names>Я. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Zhulikov</surname><given-names>Ya. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p> Жуликов Ярослав Андреевич, ординатор отделения химиотерапии № 1 1</p><p> Москва</p></bio><bio xml:lang="en"><p> Zhulikov Yaroslav A., resident of Dept of Chemotherapy No. 1 </p><p> Moscow</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-8936-3590</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Артамонова</surname><given-names>Е. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Artamonova</surname><given-names>E. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p> Артамонова Елена Владимировна, д. м. н., зав. отделением химиотерапии № 1 1 , проф. кафедры онкологии, зав. кафедрой онкологии и торакальнойхирургии</p><p> Москва</p></bio><bio xml:lang="en"><p> Artamonova Elena V., DM Sci (habil.), head of Dept of Chemotherapy No. 1 1 , professor at Dept of Oncology, head of Dept of Oncology and Thoracic Surgery</p><p>Moscow</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-3770-5173</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Хорошилов</surname><given-names>М. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Khoroshilov</surname><given-names>M. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p> Хорошилов Максим Викторович, ординатор отделения химиотерапии № 1 1</p><p> Москва</p></bio><bio xml:lang="en"><p> Khoroshilov Maxim V., resident of Dept of Chemotherapy No. 1 </p><p>Moscow</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7514-280X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Петровский</surname><given-names>А. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Petrovskiy</surname><given-names>A. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p> Петровский Александр Валерьевич, к. м. н., врач-онколог, врач-хирург, зам. директора по образовательной деятельности, зав. хирургическим отделением № 15 (комбинированного лечения опухолей молочной железы) НИИ клинической  онкологии , доцент кафедры онкологии лечебного факультета</p><p> Москва</p></bio><bio xml:lang="en"><p> Petrovsky Alexander V., PhD Med, oncologist, surgeon, deputy director of educational activities, head of Surgical Dept No. 15 (combined treatment of breast tumors) of Research Institute of Clinical Oncology , associate professor at Dept of Oncology of Faculty of MedicineMoscow</p></bio><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-2572-2547</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Денчик</surname><given-names>Д. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Denchik</surname><given-names>D. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p> Денчик Данила Александрович, к. м. н., н. с. хирургического отделения № 15</p><p> Москва</p></bio><bio xml:lang="en"><p> Denchik Danila A., PhD Med, researcher at Surgical Dept No. 15</p><p> Moscow</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3162-2964</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Дружинина</surname><given-names>Д. И.</given-names></name><name name-style="western" xml:lang="en"><surname>Drujinina</surname><given-names>D. I.</given-names></name></name-alternatives><bio xml:lang="ru"><p> Дружинина Диана Ильясовна, клинический ординатор онкологического отделения лекарственных методов лечения (химиотерапевтического № 1) НИИ клинической онкологии</p><p> Москва</p></bio><bio xml:lang="en"><p> Druzhinina Diana I., resident of Oncology Dept of Drug Methods of Treatment (Chemotherapy No. 1) of Research Institute of Clinical Oncology</p><p>Moscow</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-6699-0738</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Воротников</surname><given-names>И. К.</given-names></name><name name-style="western" xml:lang="en"><surname>Vorotnikov</surname><given-names>I. K.</given-names></name></name-alternatives><bio xml:lang="ru"><p> Воротников Игорь Константинович, д. м. н., проф., в. н. с. хирургического отделения № 15</p><p> Москва</p></bio><bio xml:lang="en"><p> Vorotnikov Igor K., DM Sci (habil.), professor, leading researcher at Surgical Dept No. 15</p><p>Moscow</p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБУ «Национальный медицинский исследовательский центр онкологии имени Н. Н. Блохина» Минздрава России</institution><country>Россия</country></aff><aff xml:lang="en"><institution>National Medical Research Centre of Oncology n.a. N. N. Blokhin</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>ФГБУ «Национальный медицинский исследовательский центр онкологии имени Н. Н. Блохина» Минздрава России; ФГАОУ ВО «Российский национальный исследовательский медицинский университет имени Н. И. Пирогова» Минздрава России; ГБУЗ МО «Московский областной научно-исследовательский клинический институт имени&#13;
М. Ф. Владимирского»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>National Medical Research Centre of Oncology n.a. N. N. Blokhin; Russian National Research Medical University n.a. N. I. Pirogov; Moscow Regional Research Clinical Institute n.a. M. F. Vladimirsky</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>ФГБУ «Национальный медицинский исследовательский центр онкологии имени Н. Н. Блохина» Минздрава России; ФГАОУ ВО «Первый Московский государственный медицинский университет имени И. М. Сеченова» Минздрава России (Сеченовский университет)</institution><country>Россия</country></aff><aff xml:lang="en"><institution>National Medical Research Centre of Oncology n.a. N. N. Blokhin; First Moscow State Medical University n.a. I. M. Sechenov</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2023</year></pub-date><pub-date pub-type="epub"><day>29</day><month>06</month><year>2023</year></pub-date><volume>0</volume><issue>10</issue><issue-title>Диагностика и онкотерапия (1)</issue-title><fpage>11</fpage><lpage>17</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Коваленко Е.И., Жуликов Я.А., Артамонова Е.В., Хорошилов М.В., Петровский А.В., Денчик Д.А., Дружинина Д.И., Воротников И.К., 2023</copyright-statement><copyright-year>2023</copyright-year><copyright-holder xml:lang="ru">Коваленко Е.И., Жуликов Я.А., Артамонова Е.В., Хорошилов М.В., Петровский А.В., Денчик Д.А., Дружинина Д.И., Воротников И.К.</copyright-holder><copyright-holder xml:lang="en">Kovalenko E.I., Zhulikov Y.A., Artamonova E.V., Khoroshilov M.V., Petrovskiy A.V., Denchik D.A., Drujinina D.I., Vorotnikov I.K.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.med-alphabet.com/jour/article/view/3154">https://www.med-alphabet.com/jour/article/view/3154</self-uri><abstract><p>Введение. Неоадъювантная химиотерапия (НАХТ) является стандартом лечения ТН РМЖ начиная с самых ранних стадий, а достижение полного лечебного патоморфоза (pCR) ассоциировано не только с достоверным увеличением бессобытийной и общей выживаемости, но и напрямую влияет на дальнейшую лечебную тактику. При отсутствии pCR назначается еще и адъювантная терапия, тогда как в случае достижения pCR дополнительное лекарственное лечение не проводится. Несмотря на большое число исследований, посвященных НАХТ ТН подтипа РМЖ, использование в опубликованных работах схем химиотерапии, различающихся как по составу препаратов, так и по режимам их дозирования, затрудняет интерпретацию результатов и выбор наиболее эффективного варианта лечения для клинической практики.Цель исследования. Изучение эффективности дозоинтенсивной НАХТ по схеме 4ddAC, затем 12 еженедельных введений паклитаксела и карбоплатина при ТН РМЖ по частоте pCR и системе RCB; определение предиктивных факторов эффективности данного режима НАХТ и влияния дозоинтенсивности лечения на частоту pCR.Методы. В проспективное однорукавное исследование включены 154 пациентки с ТН РМЖ, получившие дозоинтенсивную НАХТ по вышеуказанной схеме с января 2017 по март 2022 года. 58,5 % пациенток имели III стадию заболевания, 21,4 % – поражение лимфоузлов уровня N 3.Результаты. Частота pCR (RCB 0) составила 53,25 % (n = 82), RCB 0–I – 66,88 % (n = 103) и была выше при Т1–2 vs T3–4 (75,90 и 56,3 %; р =0,020), прогрессирование заболевания наблюдалось у 3,25 % (n = 4). При операбельном раке частота pCR составила 58,60 %, при местнораспространенном – 47,60 %. Герминальные мутации в генах BRCA1/2 выявлены в 21,43 % (n = 33), наиболее часто встречаемой мутацией была BRCA1 5382insC – 63,64 % (21/33). На долю редких мутаций (выявленных с помощью NGS) пришлось 30,3 % (n = 10). Единственным фактором, ассоциированным с достоверным увеличением частоты pCR, был возраст ≤ 50 лет (p = 0,010), отмечена тенденция к повышению частоты pCR в подгруппах T1–2 (p = 0,052) и BRCA1/2 mut (p = 0,080). Редукция дозы выполнялась только в связи с развитием нежелательных явлений II–III степени, при этом влияния дозоинтенсивности на достижение pCR не выявлено.Выводы. Данное исследование является наиболее крупным по изучению эффективности НАХТ по схеме 4 ddAC, затем 12 PC при ТН РМЖ. Режим позволяет добиться высокой частоты pCR, несмотря на большой удельный вес пациенток с местнораспространенным РМЖ. Высокая частота редких мутаций в генах BRCA1/2 и потенциальная терапевтическая значимость этого маркера при сохранении резидуальной болезни диктуют необходимость выполнения NGS всем пациенткам с ТН РМЖ.</p></abstract><trans-abstract xml:lang="en"><sec><title>Introduction</title><p>Introduction. Neoadjuvant chemotherapy (NACT) is the standard of care for II–III stages of TN BC. Complete pathomorphological response (pCR) is associated with a signifiant increase in event-free and overall survival. In addition, in the absence of pCR, post-neoadjuvant adjuvant therapy is prescribed, while if pCR is achieved, additional treatment is not carried out. Despite a large number of studies on NACT of TN BC, different NACT regimens in various clinical trials make it diffiult to interpret their results.</p></sec><sec><title>Objective</title><p>Objective. To investigate the effiacy of 4ddAC followed by 12 weekly cycles of paclitaxel and carboplatin in TN BC (according to the RCB system and the frequency of pCR); determine the predictive factors for the effectiveness of this chemotherapy regimen, and the effect of dose intensity on the pCR rate.</p></sec><sec><title>Methods</title><p>Methods. This prospective study included 154 patients with TN breast cancer who received dose-dence neoadjuvant chemotherapy from January 2017 to March 2022.</p></sec><sec><title>Results</title><p>Results. PCR rate was 53.25 % (n = 82), RCB 0–I was 66.88 % (n = 103), disease progression was observed in 3.25 % (n = 4). The frequency of germline mutations in the BRCA1/2 genes was 21.43 % (n = 33). The most common mutation was BRCA1 5382insC – 63.64 % (n = 21) of all BRCA1/2 mutations. Rare mutations detected by NGS accounted for 30.3 % (n = 10). The only factor associated with a signifiant increase in the pCR rate was age ≤50 years (p = 0.010), there was a trend towards an increase pCR rate in the subgroups T1–2 (p = 0.052) and BRCA1/2 mut (p = 0.080). There was no effect of the dose intensity on the achievement of pCR.</p></sec><sec><title>Conclusions</title><p>Conclusions. This retrospective analysis is the largest study evaluating the effiacy of 4 ddAC followed by 12 PC in NACT TN BC. The regimen allows to achieve a high frequency of pCR, despite the large proportion of patients with locally advanced breast cancer. The high frequency of rare mutations in the BRCA1/2 genes and the potential therapeutic signifiance of this marker in residual disease treatment dictates the need for NGS in all patients with TN in breast cancer.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>неоадъювантная химиотерапия</kwd><kwd>тройной негативный рак молочной железы</kwd><kwd>BRCA1/2</kwd><kwd>дозоуплотненные режимы химиотерапии</kwd><kwd>препараты платины</kwd></kwd-group><kwd-group xml:lang="en"><kwd>neoadjuvant chemotherapy</kwd><kwd>triple negative breast cancer</kwd><kwd>BRCA1/2</kwd><kwd>dose-dense chemotherapy regimens</kwd><kwd>platinum agents</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Sørlie T, Perou CM, Tibshirani R et al. 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