medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2022-16-9-201-206medsovet-6934Research ArticleКЛИНИЧЕСКОЕ НАБЛЮДЕНИЕCLINICAL OBSERVATIONВозможности терапии метастатического тройного негативного рака молочной железыTherapy options for metastatic triple negative breast cancerhttps://orcid.org/0000-0002-1459-2292ГлазковаЕ. В.GlazkovaE. V.

Глазкова Елена Владимировна – кандидат медицинских наук, врач-онколог онкологического отделения лекарственных методов лечения (химиотерапевтического) №1.

115478, Москва, Каширское шоссе, д. 24.

Elena V. Glazkova - Cand. Sci. (Med.), Oncologist, Cancer Drug Therapy (Chemotherapeutic) Department No. 1, Blokhin National Medical Research Center of Oncology.

24, Kashirskoye Shosse, Moscow, 115478.

mdglazkova@gmail.comhttps://orcid.org/0000-0002-8149-0085ФроловаМ. А.FrolovaM. A.

Фролова Мона Александровна – доктор медицинских наук, ведущий научный сотрудник онкологического отделения лекарственных методов лечения (химиотерапевтического) №1.

115478, Москва, Каширское шоссе, д. 24.

Mona A. Frolova - Dr. Sci. (Med.), Lead Research Associate, Cancer Drug Therapy (Chemotherapeutic) Department No. 1, Blokhin National Medical Research Center of Oncology.

24, Kashirskoye Shosse, Moscow, 115478.

https://orcid.org/0000-0002-6666-549XИсраелянЭ. Р.IsraelyanE. R.

Исраелян Эдгар Рудикович - ординатор кафедры онкологии факультета дополнительного профессионального образования.

119571, Москва, Ленинский проспект, д. 117.

Edgar R. Israelyan - Resident Physician, Department of Oncology, Faculty of Additional Professional Education, Pirogov National Medical Research University.

117, Leninskiy Ave., Moscow, 119571.

e.israelyan@yandex.ruНациональный медицинский исследовательский центр онкологии имени Н.Н. БлохинаРоссияBlokhin National Medical Research Center of OncologyRussian FederationРоссийский национальный исследовательский медицинский университет имени Н.И. ПироговаРоссияPirogov National Medical Research UniversityRussian Federation20221906202209201206Copyright © Глазкова Е.В., Фролова М.А., Исраелян Э.Р., 20222022Глазкова Е.В., Фролова М.А., Исраелян Э.Р.Glazkova E.V., Frolova M.A., Israelyan E.R.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/6934

Метастатический тройной негативный рак молочной железы (РМЖ) остается прогностически наиболее неблагоприятным среди всех вариантов РМЖ. Несмотря на активное внедрение в практику комбинаций цитостатиков с иммунотерапевтическими агентами, а также PARP-ингибиторов, основным методом лечения пациенток данной группы остается проведение последовательных линий химиотерапии (ХТ), медиана общей выживаемости которых не превышает 15 мес. Для данного подтипа РМЖ характерно быстрое развитие лекарственной резистентности на ранних этапах системного лечения и преимущественно висцеральный характер прогрессирования, что обуславливает низкую продолжительность жизни пациенток. Применение комбинации капецитабина и иксабепилона показало свою эффективность в лечении пациенток с опухолями, резистентными к терапии таксанами и антрациклинами. Применение данной комбинации характеризуется приемлемым и управляемым профилем токсичности. В настоящей работе представлен клинический случай терапии комбинацией иксабепилона и капецитабина пациентки с прогрессированием рака молочной железы на фоне предшествующего применения таксанов, платиносодержащего дуплета ХТ и эрибулина. Данный подход совместно с проведением симптоматических лапа-роцентезов и плевродеза позволил обеспечить общую выживаемость, превысившую 45 мес., с сохранением удовлетворительного функционального статуса пациентки.

Metastatic triple-negative breast cancer remains the most unfavourable among all breast cancer subtypes from the prognostic point of view. Despite the active introduction into practice of combinations of cytostatics with immunotherapeutic agents, as well as PARP inhibitors, sequential lines of chemotherapy with the median overall survival which does not exceed 15 months remains the main method of treating patients in this group. This breast cancer subtype is characterized by a rapid development of drug resistance at the early stages of systemic treatment and a predominantly visceral progression, which determines a low life expectancy in patients. The combination of capecitabine and ixabepilone has proved to be effective in the treatment of tumours that are resistant to taxanes and anthracyclines. The use of this combination is characterized by an acceptable and controlled toxicity profile. This article presents a clinical case of therapy with a combination of ixabepilone and capecitabine of a patient with breast cancer progression during the previous therapy of taxanes, a platinum-based doublet chemotherapy and eribulin. This approach, together with symptomatic laparocentesis and pleurodesis, allowed for overall survival exceeding 45 months with the preservation of a satisfactory functional status of the patient.

тройной негативный рак молочной железыхимиотерапияиксабепилонкапецитабинплевродезтоксичностьtriple negative breast cancerchemotherapyixabepilonecapecitabinepleurodesistoxicityReferencesDent R., Hanna W.M., Trudeau M., Rawlinson E., Sun P., Narod S.A. Pattern of metastatic spread in triple-negative breast cancer. Breast Cancer Res Treat. 2009;115(2):423-428. https://doi.org/10.1007/s10549-008-0086-2.Dent R., Hanna W.M., Trudeau M., Rawlinson E., Sun P., Narod S.A. Pattern of metastatic spread in triple-negative breast cancer. Breast Cancer Res Treat. 2009;115(2):423-428. https://doi.org/10.1007/s10549-008-0086-2.Lu Y.-S., Im S.-A., Colleoni M., Franke F., Bardia A., Cardoso F. et al. Updated Overall Survival of Ribociclib plus Endocrine Therapy versus Endocrine Therapy Alone in Pre- and Perimenopausal Patients with HR + /HER2 -Advanced Breast Cancer in MONALEESA-7: A Phase III Randomized Clinical Trial. Clin Cancer Res. 2022:28(5):851-859. https://doi.org/10.1158/1078-0432.CCR-21-3032.Lu Y.-S., Im S.-A., Colleoni M., Franke F., Bardia A., Cardoso F. et al. Updated Overall Survival of Ribociclib plus Endocrine Therapy versus Endocrine Therapy Alone in Pre- and Perimenopausal Patients with HR + /HER2 -Advanced Breast Cancer in MONALEESA-7: A Phase III Randomized Clinical Trial. Clin Cancer Res. 2022:28(5):851-859. https://doi.org/10.1158/1078-0432.CCR-21-3032.Schmid P., Adams S., Rugo H.S., Schneeweiss A., Barrios C.H., Iwata H. et al. Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N Engl J Med. 2018;379(22):2108-2121. https://doi.org/10.1056/NEJMoa1809615.Schmid P., Adams S., Rugo H.S., Schneeweiss A., Barrios C.H., Iwata H. et al. Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N Engl J Med. 2018;379(22):2108-2121. https://doi.org/10.1056/NEJMoa1809615.Miles D., Gligorov J., Andre F., Cameron D., Schneeweiss A., Barrios C. et al. Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer. Ann Oncol. 2021;32(8):994-1004. https://doi.org/10.1016/j.annonc.2021.05.801.Miles D., Gligorov J., Andre F., Cameron D., Schneeweiss A., Barrios C. et al. Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer. Ann Oncol. 2021;32(8):994-1004. https://doi.org/10.1016/j.annonc.2021.05.801.Cortes J., Cescon D.W., Rugo H.S., Nowecki Z., Im S.-A., Yusof M.M. et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triplenegative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020;396(10265):1817-1828. https://doi.org/10.1016/S0140-6736(20)32531-9.Cortes J., Cescon D.W., Rugo H.S., Nowecki Z., Im S.-A., Yusof M.M. et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triplenegative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020;396(10265):1817-1828. https://doi.org/10.1016/S0140-6736(20)32531-9.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.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.Kaufman P.A., Awada A., Twelves C., Yelle L., Perez E.A., Velikova G. et al. Phase III Open-Label Randomized Study of Eribulin Mesylate Versus Capecitabine in Patients With Locally Advanced or Metastatic Breast Cancer Previously Treated With an Anthracycline and a Taxane. J Clin Oncol. 2015;33(6):594-601. https://doi.org/10.1200/JCO.2013.52.4892.Kaufman P.A., Awada A., Twelves C., Yelle L., Perez E.A., Velikova G. et al. Phase III Open-Label Randomized Study of Eribulin Mesylate Versus Capecitabine in Patients With Locally Advanced or Metastatic Breast Cancer Previously Treated With an Anthracycline and a Taxane. J Clin Oncol. 2015;33(6):594-601. https://doi.org/10.1200/JCO.2013.52.4892.Tutt A., Tovey H., Cheang M.C.U., Kernaghan S., Kilburn L., Gazinska P. et al. A randomised phase III trial of carboplatin compared with docetaxel in BRCA1/2 mutated and pre-specified triple negative breast cancer “BRCAness” subgroups: the TNT Trial. Nat Med. 2018;24(5):628-637. https://doi.org/10.1038/s41591-018-0009-7.Tutt A., Tovey H., Cheang M.C.U., Kernaghan S., Kilburn L., Gazinska P. et al. A randomised phase III trial of carboplatin compared with docetaxel in BRCA1/2 mutated and pre-specified triple negative breast cancer “BRCAness” subgroups: the TNT Trial. Nat Med. 2018;24(5):628-637. https://doi.org/10.1038/s41591-018-0009-7.Robson M.E., Tung N., Conte P., Im S.-A., Senkus E., Xu B. et al. OlympiAD final overall survival and tolerability results: Olaparib versus chemotherapy treatment of physician's choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer. Ann Oncol. 2019;30(4):558-566. https://doi.org/10.1093/annonc/mdz012.Robson M.E., Tung N., Conte P., Im S.-A., Senkus E., Xu B. et al. OlympiAD final overall survival and tolerability results: Olaparib versus chemotherapy treatment of physician's choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer. Ann Oncol. 2019;30(4):558-566. https://doi.org/10.1093/annonc/mdz012.Litton J.K., Hurvitz S.A., Mina L.A., Rugo H.S., Lee K.-H., Goncalves A. et al. Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial. Ann Oncol. 2020;31(11):1526-1535. https://doi.org/10.1016/j.annonc.2020.08.2098.Litton J.K., Hurvitz S.A., Mina L.A., Rugo H.S., Lee K.-H., Goncalves A. et al. Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial. Ann Oncol. 2020;31(11):1526-1535. https://doi.org/10.1016/j.annonc.2020.08.2098.Perez E.A., Lerzo G., Pivot X., Thomas E., Vahdat L., Bosserman L. et al. Efficacy and Safety of Ixabepilone (BMS-247550) in a Phase II Study of Patients With Advanced Breast Cancer Resistant to an Anthracycline, a Taxane, and Capecitabine. J Clin Oncol. 2007;25(23):3407-3414. https://doi.org/10.1200/JCO.2006.09.3849.Perez E.A., Lerzo G., Pivot X., Thomas E., Vahdat L., Bosserman L. et al. Efficacy and Safety of Ixabepilone (BMS-247550) in a Phase II Study of Patients With Advanced Breast Cancer Resistant to an Anthracycline, a Taxane, and Capecitabine. J Clin Oncol. 2007;25(23):3407-3414. https://doi.org/10.1200/JCO.2006.09.3849.Thomas E.S., Gomez H.L., Li R.K., Chung H.-C., Fein L.E., Chan V.F. et al. Ixabepilone Plus Capecitabine for Metastatic Breast Cancer Progressing After Anthracycline and Taxane Treatment. J Clin Oncol. 2007;25(33):5210-5217. https://doi.org/10.1200/JCO.2007.12.6557.Thomas E.S., Gomez H.L., Li R.K., Chung H.-C., Fein L.E., Chan V.F. et al. Ixabepilone Plus Capecitabine for Metastatic Breast Cancer Progressing After Anthracycline and Taxane Treatment. J Clin Oncol. 2007;25(33):5210-5217. https://doi.org/10.1200/JCO.2007.12.6557.Rugo H.S., Roche H., Thomas E., Chung H.C., Lerzo G.L., Vasyutin I. et al. Efficacy and Safety of Ixabepilone and Capecitabine in Patients With Advanced Triple-negative Breast Cancer: a Pooled Analysis From Two Large Phase III, Randomized Clinical Trials. Clin Breast Cancer. 2018;18(6):489-497. https://doi.org/10.1016/j.clbc.2018.07.024.Rugo H.S., Roche H., Thomas E., Chung H.C., Lerzo G.L., Vasyutin I. et al. Efficacy and Safety of Ixabepilone and Capecitabine in Patients With Advanced Triple-negative Breast Cancer: a Pooled Analysis From Two Large Phase III, Randomized Clinical Trials. Clin Breast Cancer. 2018;18(6):489-497. https://doi.org/10.1016/j.clbc.2018.07.024.Vahdat L.T., Thomas E.S., Roche H.H., Hortobagyi G.N., Sparano J.A., Yelle L. et al. Ixabepilone-associated peripheral neuropathy: data from across the phase II and III clinical trials. Support Care Cancer. 2012;20(11):2661-2668. https://doi.org/10.1007/s00520-012-1384-0.Vahdat L.T., Thomas E.S., Roche H.H., Hortobagyi G.N., Sparano J.A., Yelle L. et al. Ixabepilone-associated peripheral neuropathy: data from across the phase II and III clinical trials. Support Care Cancer. 2012;20(11):2661-2668. https://doi.org/10.1007/s00520-012-1384-0.Valero V., Vrdoljak E., Xu B., Thomas E., Gomez H., Manikhas A. et al. Maintenance of Clinical Efficacy After Dose Reduction of Ixabepilone Plus Capecitabine in Patients With Anthracycline- and Taxane-Resistant Metastatic Breast Cancer: A Retrospective Analysis of Pooled Data From 2 Phase III Randomized Clinical Trials. Clin Breast Cancer. 2012;12(4):240-246. https://doi.org/10.1016/j.clbc.2012.03.013.Valero V., Vrdoljak E., Xu B., Thomas E., Gomez H., Manikhas A. et al. Maintenance of Clinical Efficacy After Dose Reduction of Ixabepilone Plus Capecitabine in Patients With Anthracycline- and Taxane-Resistant Metastatic Breast Cancer: A Retrospective Analysis of Pooled Data From 2 Phase III Randomized Clinical Trials. Clin Breast Cancer. 2012;12(4):240-246. https://doi.org/10.1016/j.clbc.2012.03.013.Kassam F., Enright K., Dent R., Dranitsaris G., Myers J., Flynn C. et al. Survival Outcomes for Patients with Metastatic Triple-Negative Breast Cancer: Implications for Clinical Practice and Trial Design. Clin Breast Cancer. 2009;9(1):29-33. https://doi.org/10.3816/CBC.2009.n.005.Kassam F., Enright K., Dent R., Dranitsaris G., Myers J., Flynn C. et al. Survival Outcomes for Patients with Metastatic Triple-Negative Breast Cancer: Implications for Clinical Practice and Trial Design. Clin Breast Cancer. 2009;9(1):29-33. https://doi.org/10.3816/CBC.2009.n.005.Sasaki T., Yasuda H., Nakayama K., Okinaga S., Suzuki T., Asada M. et al. A randomized phase II trial comparing carboplatin pleurodesis with cisplatin pleurodesis in patients with stage IIIB/IV non-small cell lung cancer (NSCLC) with malignant pleural effusions (MPE). J Clin Oncol. 2006;24(18_Suppl):17012-17012. https://doi.org/10.1200/jco.2006.24.18_suppl.17012.Sasaki T., Yasuda H., Nakayama K., Okinaga S., Suzuki T., Asada M. et al. A randomized phase II trial comparing carboplatin pleurodesis with cisplatin pleurodesis in patients with stage IIIB/IV non-small cell lung cancer (NSCLC) with malignant pleural effusions (MPE). J Clin Oncol. 2006;24(18_Suppl):17012-17012. https://doi.org/10.1200/jco.2006.24.18_suppl.17012.Bakr R.M., El-Mahalawy I.I., Abdel-Aal G.A., Mabrouk A.A., Ali A.A. Pleurodesis using different agents in malignant pleural effusion. Egypt J Chest Dis Tuber. 2012;61(4):399-404. https://doi.org/10.1016/j.ejcdt.2012.07.005.Bakr R.M., El-Mahalawy I.I., Abdel-Aal G.A., Mabrouk A.A., Ali A.A. Pleurodesis using different agents in malignant pleural effusion. Egypt J Chest Dis Tuber. 2012;61(4):399-404. https://doi.org/10.1016/j.ejcdt.2012.07.005.Badrawy M.K.E., Ali R.E.-M., Hewidy A.A., El-Layeh M.A., Akl F.M.F., Shebl A. Efficacy and safety of intrapleural cisplatin versus silver nitrate in treatment of malignant pleural effusion. Egypt J Brochol. 2018;(12):98-104. Available at: https://ejb.springeropen.com/articles/10.4103/ejb.ejb_39_17.Badrawy M.K.E., Ali R.E.-M., Hewidy A.A., El-Layeh M.A., Akl F.M.F., Shebl A. Efficacy and safety of intrapleural cisplatin versus silver nitrate in treatment of malignant pleural effusion. Egypt J Brochol. 2018;(12):98-104. Available at: https://ejb.springeropen.com/articles/10.4103/ejb.ejb_39_17.Lee J.J., Swain S.M. Peripheral Neuropathy Induced by MicrotubuleStabilizing Agents. J Clin Oncol. 2006;24(10):1633-1642. https://doi.org/10.1200/JCO.2005.04.0543.Lee J.J., Swain S.M. Peripheral Neuropathy Induced by MicrotubuleStabilizing Agents. J Clin Oncol. 2006;24(10):1633-1642. https://doi.org/10.1200/JCO.2005.04.0543.

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