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КЛИНИЧЕСКИЙ СЛУЧАЙ
DOI: 10.24412/2707-6180-2021-63-244-249 УДК 618.19:616-006.6 МРНТИ 76.29.48, 76.29.49
TRASTUZUMAB-INDUCED ACUTE CARDIOTOXIC EVENT IN BREAST CANCER
PATIENT - A CLINICAL CASE
S.K. BALMAGAMBETOVA, ZH.SH. TLEGENOVA, B.K. ZHOLDIN, G.L. KURMANALINA, I.ZH. TALIPOVA, A.K. KOYSHYBAEV, A.K. URAZOVA, D.S. NURMANOVA, O.N. URAZAYEV, G.A. SULTANBEKOVA, K.I. KUBENOVA, M.B. BASPAYEVA, S.S. MADINOVA
West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
Saule K. Balmagambetova Zhenisgul Sh. Tlegenova Bekbolat K. Zholdin Gulnara L. Kurmanalina Iliada Zh. Talipova Arip K. Koyshybaev Ainel K. Urazova Dinara S. Nurmanova Olzhas N. Urazayev Gulmira A. Sultanbekova Kulparshan I. Kubenova Mira B. Baspayeva
Citation/
библиографияльщ сттеме/ библиографическая ссылка:
Balmagambetova SK, Tlegenova ZhSh, Zholdin BK, Kurmanalina GL, Talipova IZh, Koyshybaev AK, Urazova AK, Nurmanova DS, Urazayev ON, Sultanbekova GA, Kubenova K I, Baspayeva MB, Madinova SS. Trastuzumab-induced acute cardiotoxic event in breast cancer patient - a clinical case. West Kazakhstan Medical Journal. 2021;63(4):244-249
Балм^амбетова С^, Ттегенова ЖШ, Жолдин БК, Курманалина ГЛ, Талипова ИЖ, ^ойшыбаев ЭК, Уразова АК, Нурманова ДС, Уразаев ОН, Султанбекова ГА, Кебенова ^И, Баспаева МБ, Мадинова СС. West Kazakhstan Medical Journal. 2021;63(4):244-249
БалмаFамбетова С^, Тiлегенова ЖШ, Жолдин БК, Курманалина ГЛ, Талипова ИЖ, ^ойшыбаев ЭК, Уразова АК, Нурманова ДС, Уразаев ОН, Султанбекова ГА, Кебенова ^И, Баспаева МБ, Мадинова СС. Острая кардиотоксичность индуцированная трастузумабом у больной раком молочной железы - клинический случай West Kazakhstan Medical Journal. 2021;63(4):244-249
http://orcid.org/0000-0003-4080-5383; SPIN-code: 1155-6274
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Trastuzumab-induced acute cardiotoxic event in breast cancer patient - a clinical case
S.K. Balmagambetova, Zh.Sh. Tlegenova, B.K. Zholdin, G.L. Kurmanalina, I.Zh. Talipova, A.K. Koyshybaev, A.K. Urazova, D.S. Nurmanova, O.N. Urazayev, G.A. Sultanbekova, K.I. Kubenova, M.B. Baspayeva, S.S. Madinova West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
Chemotherapy is one of the main treatments for cancer patients. Meanwhile, the frequency of cardiovascular complications associated with chemotherapy has incremented.
The report is aimed to present a case of acute cardiotoxicity developed in Breast cancer patient during the treatment with Trastuzumab.
Patient aged 61, diagnosed with left Breast cancer, was admitted to the hospital for planned chemotherapy. Oncologic diagnosis: Nodular invasive carcinoma of the left breast. St I. T1NxM0. Condition after radical mastectomy and a course of radiation treatment. Immunohistochemistry conclusion: HER-2 positive. Trastuzumab was prescribed in a routine regime, once in three weeks, course of 18 procedures. After four months of chemotherapy, she experienced weakness, a headache, dizziness, tachycardia, shortness of breath. ECG records: frequent ventricular extrasystoles, unstable ventricular tachycardia. LVEF decreased to 56% from 69% at baseline. The patient was admitted to the Cardiology division with a diagnosis of "paroxysm of ventricular tachycardia". Data on Holter monitoring: 435 episodes of paroxysm of unstable monomorphic ventricular tachycardia with a frequency of 126-206 beats/min. Treatment under conditions of Intensive Care Unit: Infusion of Santodarone 600 mg, Magnesium sulfate, Bisoprolol 5 mg. After seven days, she has discharged for further outpatient treatment with improvement. Subsequently, patient C. was transferred to the Cardiology division. Seven days later, she has discharged with improvement for further outpatient treatment with recommendations of Bisoprolol 5 mg, Valsartan 80 mg, Rosuvastatin 20 mg, Omacor 1000 mg, Trimetazidine 80 mg uptake. In total, patient C. received 13 courses of Trastuzumab instead of 18 (75%). Conclusion: Thus, the presented clinical case revealed disadvantages of the currently practiced clinical approach to cancer patients with prescribed chemotherapy: EchoCG cannot solely provide proper cardiac monitoring to prevent unfavorable cardiotoxic events successfully. New effective methods to prevent cardiotoxicity at an early stage, such as cardiac biomarkers and global longitudinal myocardial deformation
e
Balmagambetova S.K.
e-mail: sau-balmagambetova@
yandex.ru
Reœceee/
Keain myemi/ Наступила: 77.77.0007
Acccetee/ Басыаымга цабыаданды/ Принята к публикации: 00.70.0007
ISSN 2707-6180 (Print) © 2021 The Authors Published by West Kazakhstan Marat Ospanov Medical University
КЛИНИЧЕСКИЙ СЛУЧАЙ
assessment, should come into everyday practice.
Keywords: Breast cancer, cardiotoxicity, Trastuzumab, echocardiography, cardiovascular complications
Сут 6e3i обырымен ауыратын наукаста трастузумабпен индукцияланFан жiтi кардиоуыттылык - клиникалык жаFдай
СД. Балмагамбетова, Ж.Ш. Тшегенова, Б.К. Жолдин, Г.Л. Курманалина, И.Ж. Талипова, Э.К. ^ойшыбаев, А.К. Уразова, Д.С. Нурманова, О.Н. Уразаев, Г.А. Султанбекова, ^.И. Кебенова, М.Б. Баспаева, С.С. Мадинова Марат Оспанов атындагы Батыс ^аза;стан медицина университета, А;тебе, ^аза;стан
Химиотерапия онкологиялы; нау;астарды емдеудщ нeгiзгi эдютершщ бiрi болып табылады. Алайда, химиотерапиямен байланысты журек-тамыр ас;ынуларыныц жиiлiгi артып бара жатыр.
Жарияланымныц максаты - Трастузумабпен емдеу аясында суг бeзi к;aтeрлi ютмен ауыратын нау;аста дамыган жедел кардиотоксикальщ жагдайды усыну. "Сол жа; сут безгнщ обыры" диагнозымен 61 жастагы нау;ас жоспарлы химиотерапия ЖYргiзу ушн стационарга TYCтi. Онкологиялы; диагноз: сол жа; сут безшщ туйiндiк инвазивт к;aтeрлi idri. Ст I. T1NxM0. Радикалды мастэктомиядан жэне радиациялы; емдеу курсынан кeйiнгi жагдай. Иммуногистохимиялы; ;орытынды: HER2 оц к;aтeрлi iсiк.
Трастузумаб KYHдeлiктi режимде, уш аптада бiр рет, 18 процедурадан турады. Терт аилы; химиотерапиядан кейн элсiздiк, бас ауруы, бас айналу, тахикардия, ентгу пайда болды. ЭКГ-да: жиi ;арыншалы; экстрасистолалар, тура;сыз ;арыншалы; тахикардия. LVEF зерттеудщ басында 69%-дан 56%-га дейн темeндeдi. Нау;ас кардиология белiмiнe ";арыншалык; тахикардияныц пароксизмГ' диагнозымен жащызылды. Холтер мониторлау дeрeктeрi: жиiлiгi 126-206 уд/мин пароксизмальды тура;сыз мономорфты ;арыншалы; тахикардияныц 435 эпизоды. Реанимация белiмшeсi жагдайында емдеу: Сантодарон инфузиясы 600 мг, магний сульфаты, Бисопролол 5 мг. Кeйiннeн нау;ас С. белiмшeгe ауыстырылды. Жeтi куннен кейгн жа;сартумен эрi ;арай амбулаториялы; емдеуге шыгарылды, жэне мынандай ем усынылды: Бисопролол 5 мг, Валсартан 80 мг, Розувастатин 20 мг, Омакор 1000 мг, Триметазидин 80 мг. Нау;ас 18 орнына Трастузумабтыц 13 курсын алды (75%). Е^орытынды. Осылайша, усынылган клиникалы; жагдай тагайындалган химиотерапиямен онкологиялы; нау;астарга к^рп уак;ытта ;олданылатын клиникам; тэсшдщ кемшшжтергн анык;тады: тек ЭхоКГ кардиотоксикалы; кубылыстардыц алдын алу ушгн жеткшжта кaрдиомониторингтi ;амтамасыз ете алмайды. Журек биомaркeрлeрi жэне миокардтыц жahaндьщ бойлы; деформациясын багалау сия;ты ерте сатыдагы кардиоуыттылык;тыц алдын алудыц жаца тиiмдi эдiстeрi KYHдeлiктi тэжiрибeгe eнгiзiлуi тшс. Hezi3zi свздер: сут безтщ цатерлi iсiгi, кардиоуыттылыц, Трастузумаб, эхокардиография, журек-цан тамырлар асцынулары
Острая кардиотоксичность индуцированная трастузумабом у больной раком молочной железы - клинический случай
С.К. Балмагамбетова, Ж.Ш. Тлегенова, Б.К. Жолдин, Г.Л. Курманалина, И.Ж. Талипова, А.К. Койшыбаев, А.К. Уразова, Д.С. Нурманова, О.Н. Уразаев, Г.А. Султанбекова, К.И. Кубенова, М.Б. Баспаева, С.С. Мадинова Западно-Казахстанский медицинский университет имени Марата Оспанова, Актобе, Казахстан
Химиотерапия является одним из основных методов лечения онкологических больных. Между тем, частота сердечно-сосудистых осложнений, связанных с химиотерапией, увеличилась.
Целью публикации является представление случая острой кардиотоксичности, развившейся у больной раком молочной железы на фоне лечения Трастузумабом. Больная 61 года с диагнозом "рак левой молочной железы" поступила в стационар для проведения плановой химиотерапии. Онкологический диагноз: Узловой инвазивный рак левой молочной железы. Ст I. T1NxM0. Состояние после радикальной мастэктомии и курса лучевого лечения. Иммуногистохимическое заключение: HER-2 положительный рак. Трастузумаб назначен в рутинном режиме, один раз в три недели, курс 18 процедур. После четырех месяцев химиотерапии у нее появились слабость, головная боль, головокружение, тахикардия, одышка. На ЭКГ: частые желудочковые экстрасистолы,
S.K. Balmagambetova, Zh.Sh. Tlegenova, B.K. Zholdin, G.L. Kurmanalina, I.Zh. Talipova, ...
неустойчивая желудочковая тахикардия. ФВ ЛЖ снизилась до 56% с 69% в начале исследования. Больная госпитализирована в кардиологическое отделение с диагнозом "пароксизм желудочковой тахикардии". Данные холтеровского мониторирования: 435 эпизодов пароксизмальной нестабильной мономорфной желудочковой тахикардии с частотой 126-206 уд/мин. Лечение в условиях отделения реанимации: инфузии Сантодарона 600 мг, магния сульфат, Бисопролол 5 мг. В дальнейшем больная С. была переведена в отделение кардиологии, через семь дней выписана с улучшением на дальнейшее амбулаторное лечение. Рекомендовано принимать: Бисопролол 5 мг, Валсартан 80 мг, Розувастатин 20 мг, Омакор 1000 мг, Триметазидин 80 мг.
Всего пациент С. получила 13 курсов Трастузумаба вместо 18 (75%). Заключение. Таким образом, представленный клинический случай выявил недостатки практикуемого в настоящее время клинического подхода к онкологическим больным с назначенной химиотерапией: только лишь ЭхоКГ не может обеспечить адекватный кардиомониторинг для успешного предотвращения неблагоприятных кардиотоксических явлений. В повседневную практику должны войти новые эффективные методы профилактики кардиотоксичности на ранней стадии, такие как сердечные биомаркеры и оценка глобальной продольной деформации миокарда.
Ключевые слова: рак молочной железы, кардиотоксичность, Трастузумаб, эхокардиография, сердечно-сосудистые осложнения
Background
Among the causes of death, oncologic diseases rank second after cardiovascular (CV) diseases. By 2030, new cancer cases are expected to rise to 23.6 million per year [1].
The high effectiveness of modern chemotherapy has made it possible to achieve great success in cancer treatment. Overall, the 5-year survival rate in the early stages of Breast cancer (BC) has reached 89% globally [24]. In Kazakhstan, the relative survival rate for BC ranges within 28.7% [5].
Reportedly, the incidence of malignant neoplasms amounted to 195.7 cases per 100,000 by 2018 in Kazakhstan, and Breast cancer ranked 1st in the structure of morbidity (12.6%). But specialists in Public health expect BC detection in the Republic of Kazakhstan to be increased by another 33% by 2022 due to improved screening [6].
Chemotherapy is one of the main treatments for cancer patients. Meanwhile, the frequency of cardiovascular (CV) complications associated with chemotherapy has incremented. About 25 million patients living after chemotherapy in Europe and the USA suffer primarily from cardiovascular disease, not from tumor consequences [7]. It has been proven that the clinical efficacy of chemotherapy is limited by the cardiotoxic effect on the heart and blood vessels with accelerated development of chronic heart failure, rhythm and conduction disturbances, a tendency to thrombosis, etc. [8]. Regrettably, expectations concerning the absence of severe cardiologic complications during chemotherapy with highly effective targeted drugs, presented by two main classes: monoclonal antibodies (Trastuzumab, Bevacizumab) and small molecules - tyrosine kinase inhibitors (Lapatinib, Imatinib, Sorafenib, Sunitinib) did not come true. Targeted antitumor therapy also leads to venous and arterial thrombosis and thromboembolism, arterial hypertension, and heart failure, especially in patients with prior cardiovascular disease [9]. Up to 3% of
BC patients treated with Trastuzumab experience severe cardiotoxic complications, while the combined uptake of Anthracycline and Trastuzumab leads to a 7-fold increase in chronic heart failure risk (CHF) [10].
Pharmaceuticals for BC chemotherapy can cause as early as delayed (late-onset) cardiotoxic effects. Acute cardiotoxicity manifests mainly through changes on the ECG, while delayed cardiomyopathy leads to dysfunction of the left ventricle with subsequent development of heart failure [11].
The Trastuzumab-induced cardiotoxicity is reversible due to its relatively favorable safety profile, unlike the irreversible Anthracycline-induced one [12]. As known, the only method to prevent unfavorable CV events is aggressively monitoring for symptoms as chemotherapy is administered, with continuing follow-up after completion of a course or the entire treatment [13].
The report is aimed to present a case of acute cardiotoxicity developed in Breast cancer patient during the treatment with monoclonal antibodies (Trastuzumab) in the Chemotherapy division of the Aktobe Oncologic center.
Case-report
Patient C., a woman aged 61, diagnosed with left-sided Breast cancer, was admitted to the hospital on January 17, 2020, for planned chemotherapy treatment. She had been recorded in the Cancer register (Electronic register of oncologic patients) since May 27, 2019, upon verifying her diagnosis and first admission to the Oncologic center. According to her diagnosis, she had a relevant history of surgical treatment - uneventful radical mastectomy of the left mammary gland seven months ago (12.06.2019), followed by adjuvant radiation treatment. Other data from the medical history: postmenopausal status, and presence of two CV risk factors - arterial hypertension and obesity (BMI 34 kg/m2). Charlson comorbidity index - 6 scores due to the presence of moderate liver damage. Baseline data at the admission examination: general condition is satisfactorily, blood pressure (BP) - 110/70,
heart rate (HR) - 66 per minute. The patient received cardioprotective treatment - Micardis Plus (Telmisartan and Hydrochlorothiazide) in a dose of 80/25 on a regular basis before the admission to the hospital due to the presence of arterial hypertension. Baseline ECG was normal, left ventricular ejection fraction (LVEF) - 69% (within normal values).
Oncologic diagnosis: Nodular invasive carcinoma of the left breast. St I. T1NxM0. Condition after radical mastectomy and a course of radiation treatment.
Immunohistochemistry (IHC) conclusion: KI-67> 45%; ER, PR - 0; HER-2 neu +3 (HER-2 positive). Based on IHC data, Trastuzumab was prescribed in a routine regime, 8 mg per each kilogram of body weight for the first time, then - 6 mg/kg intravenously once in three weeks, course of 18 procedures.
The patient continued her cardioprotective treatment with Micardis Plus during chemotherapy procedures in out-patient clinic. After four months of chemotherapy treatment with Trastuzumab, she felt a worsening of her condition; the disease onset was almost sudden. She experienced weakness, a headache, dizziness, tachycardia, shortness of breath. Arterial pressure raised to 150/100, HR - 88 per minute. ECG records: Sinus rhythm 85, frequent ventricular extrasystoles, unstable ventricular tachycardia, severe violations of repolarization. LVEF decreased to 56%. Due to the mentioned symptoms onset, she was emergently admitted to the Cardiology division on May 26, 2020, with the diagnosis of ventricular tachycardia, where specialists started cardiologic aid immediately. Severe violations of the heart rhythm on the ECG are depicted in Figure 1.
Пример ЭКГ максимальной ЧСС за время наблюдения (176 уд/м 28 май 13:27:23)
Figure 1. Unstable ventricular tachycardia in patient with Trastuzumab-induced cardiotoxicity
On May 28, 2020, a clinical diagnosis was established: (111.0) Hypertensive disease with predominant heart disease and congestive heart failure.
Basic DS: Arterial hypertension of the third degree. Risk 4.
Complications: Ventricular extrasystoles of the fifth grade according to Ryan. Paroxysm of ventricular tachycardia.
Accompanying: Univascular lesion of the coronary bed. Carcinoma of the left breast St IA. pTINoMo. Condition after surgical treatment (06/12/2019). Condition
after combined treatment (13 courses of chemotherapy, 1 course of radiation therapy). Fibroadenoma of the right breast.
Analyzes on admission: Troponin 0.03 ng/ml; Creatinine 100 p,mol/l, Glucose 6.1 mmol/l, Potassium 3.7 mmol/l, C-reactive protein (CRP) 8.4 mg/l; leukocytes 7.98*109/1, hemoglobin 125 g/l, hematocrit 38%, platelets 162, ESR 40 mm/h.
Due to ventricular tachycardia and other cardiac arrhythmias (see Holter monitoring data), the patient was prescribed specific treatment.
Статистик! нарушений рнтмя сердца
Название всего за кто в час RR (мс) Длина (компл.) ЧСС (уд/мин) Продолжительность
Период muí. 1 макс. |средн. от 1 до среда мин. 1 макс. минимум ¡максимум
Синусовый Р1ГГМ
■ ■■ ■ Одиночные желудочковые жтрасистолы
всё измер. 3300 25 146 265 720 489
бодр. 3183 31 141 265 693 487
сон 117 4 440 720 546
— Парные желудочковые мономорфные жтрасистолы
всё измер. 9761 75 432 249 669 449
бодр. 9754 95 431 249 669 449
сон 7 0 440 490 465
.....Групповые желудочковые мономорфные жтрасистолы с высокой ЧСС (пароксизмы тахикардии)
всё измер. 4256 33 188 218 556 368 3 4 3 127 216 île 1с
бодр. 4256 41 188 218 556 368 3 4 3 127 216 <1с 1с
.....Пароиишы желудочковой мономорфной шика йдии
всё измер. 435 3 19 237 549 342 5 22 6 126 206 1с 6с
бодр. 435 4 19 237 549 342 5 22 6 126 206 1с 6с
- - - Одиночные паджелудочшые жтрасистолы
всё измер. 11 0 0 354 739 504
бодр. 7 0 0 354 584 472
сон 4 0 428 739 560
■ ■ ■ Парные наджелрочковые жтрасистолы
всё измер. 3 0 0 307 451 388
бодр. 3 0 0 307 451 388
Figure 2. Data on Holter monitoring
Data of Holter monitoring: Ventricular ectopic activity is pathological - 3300 single extrasystoles of one morphology, 9761 monomorphic pairs, 4256 monomorphic groups and 435 episodes of paroxysm of unstable monomorphic ventricular tachycardia with a frequency of 126-206 beats/min.
Treatment under conditions of Cardiological Intensive Care Unit was carried out:
Infusion of Santodarone 600 mg, Magnesium sulfate, Bisoprolol 5 mg.
Later, patient C. spent seven days in the Cardiology division. On June 6, 2020, she was examined jointly with a head of the division: At the time of examination, there was no pain syndrome, no dyspnea at rest. The condition is satisfactory. Vesicular breathing in the lungs, no wheezing. The heart sounds are muffled, the rhythm is correct. Heart rate - 60 beats/min. BP 120/70 mm Hg. The abdomen is soft and painless. The liver and spleen are not enlarged. There is no peripheral edema. Physiological functions are not disturbed. The patient is discharged for further outpatient treatment with improvement; recommendations have been made: Bisoprolol 5 mg, Valsartan 80 mg, Rosuvastatin 20 mg, Omacor 1000 mg, Trimetazidine 80 mg.
Chemotherapy was interrupted. In total, C. received 13 courses of Trastuzumab instead of 18 (75%). The following served as the basis for identifying a cardiotoxic complication (indicated in Cancer register): Decreased LVEF> 10%, ventricular extrasystoles, unstable
S.K. Balmagambetova, Zh.Sh. Tlegenova, B.K. Zholdin, G.L. Kurmanalina, I.Zh. Talipova,
ventricular tachycardia.
On August 31, 2021, the death occurred after 26 months of treatment. The death cause - COVID-19.
Comments on the presented case
Although the death cause is indicated as COVID-19, there are many reasons to believe that developed in patient acute and then chronic Trastuzumab-induced cardiotoxicity significantly contributed to such unfavorable outcomes. As mentioned, CV diseases can lead to the death of cancer survivors. Such events can occur due to the direct effect of anticancer therapy, i.e. cardiotoxicity of prescribed medication, or accelerating the development of cardiac dysfunction in the presence of conventional CV risk factors [14]. The risk of left ventricular dysfunction or the development of heart failure in patients with existing CV risk factors increases with the administration of tyrosine kinase inhibitors; prescribing Trastuzumab simultaneously with or after Anthracyclines, or even without them; with radiation therapy in combination with chemotherapy, especially with cancer of the left breast; when prescribing VEGF inhibitors [15].
In the presented case, two CV risk factors were present in the patient long before the medication with Trastuzumab - obesity and arterial hypertension. Besides, C. underwent a course of radiation therapy on the left breast area.
Although the frequency of the chemotherapy cardiotoxic effects depends mainly on the class of drugs prescribed, there are other predisposing factors. Among them, poor compliance with cardiac monitoring recommendations can take place [16].
As known, echocardiographic monitoring of the CV system is an essential part in cardiac patient management [7]. EchoCG is recognized as a reliable method to monitor cardiac function, although the data on cardiac markers supremacy emerged [12]. Regrettably, LVEF, albeit being considered a good predictor of CV outcomes, lacks the sensitivity to detect early subclinical changes in cardiac function. In patient C., cardiac monitoring was performed through LVEF proceeding assessment, and we found a significant decreasing the LVEF values of 11%. Still, undertaken measures were insufficient to prevent the acute cardiotoxic event. Reportedly, a more sensitive marker for predicting dysfunction of the left ventricle in patients during and after cancer therapy is an assessment of global longitudinal myocardial deformation [17].
Recent researches point to cardiac troponin as a helpful mean for early assessment and monitoring of CV events [18]. Unlike patients with acute myocardial infarction,
patients receiving chemotherapy require long-term monitoring of troponin levels. Monitoring troponin levels increases the cost of treatment but allows identifying patients with a high risk of developing cardiotoxic complications of chemotherapy who will need to carry out stricter monitoring of the cardiovascular system using imaging techniques, including the assessment of global longitudinal left ventricular deformity [19, 20]. Researchers recognize this approach as the most promising because it will allow identifying cardiotoxicity at the subclinical stage and prescribing preventive therapy to slow the progression of left ventricular dysfunction and prevent interruption of anticancer treatment [21].
Conclusion
Thus, the presented clinical case revealed disadvantages of the currently practiced clinical approach to cancer patients with prescribed chemotherapy: EchoCG cannot solely provide proper cardiac monitoring to prevent unfavorable cardiotoxic events successfully. In the long run, the management of cancer patients should be revised from the Cardioncology point of view. New effective methods to prevent cardiotoxicity at an early stage, such as cardiac biomarkers and global longitudinal myocardial deformation assessment, should come into everyday practice.
List of all contributing authors
SB, ZT and BZ were responsible for general editing of the manuscript and key issues of the report presentation. SB was major contributor to writing all sections of the manuscript. GK, IT and AK were responsible for editing the "Background" section. AU, DN, OU and GS were responsible for selection of references and participated in searching the medical records. KK, MB and SM were responsible for data curation and validation.
All authors read and approved the final manuscript.
Acknowledgements
The work was carried out within the framework of a scientific project with grant funding from the Science Committee of the Ministry of Education and Science of the Republic of Kazakhstan "Development of a Program for early diagnosis and treatment of cardiotoxic complications caused by Breast cancer chemotherapy" (IRN AP09259524, state reg. No. 0121PK00565).
The authors declare that they have no conflicts of interest.
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