Effects of Anthracyclines on Atherosclerosis in Patients with Breast Cancer and Protective Effect of Dexrazoxane

Effects of Anthracyclines on Atherosclerosis in Patients with Breast Cancer and Protective Effect of Dexrazoxane | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effects of Anthracyclines on Atherosclerosis in Patients with Breast Cancer and Protective Effect of Dexrazoxane Demet Isik Bayraktar, Recep Turkel, Guzin Demirag This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6990789/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Anthracyclines are used as the main agents for the treatment of breast cancer. Dexrazoxane is one of the main agents used to prevent the cardiotoxic effect of anthracyclines. In this study, the effect of anthracyclines on arteriosclerosis were investigated. Materials and Methods Sixty patients were included the study who were diagnosed with breast cancer and aged between 23–58. The patients were divided into two groups by evaluating their age, cancer type, cancer grade and the treatments they received. The study group consisted of 30 patients with breast cancer who received dexrazoxane and the control group consisted of the patients who were similar to the study group and did not receive. Basal oscillometric arterial and echocardiographic cardiac parameters, aortic stiffness and pulse wave velocity (PWV) values of all patients were measured before chemotherapy and 1 month after the chemotherapy protocols were completed. Results In the study group receiving dexrazoxane, only left ventricular end-diastolic pressure increased in oscillometric and echocardiographic measurements before and after treatment (p = 0.008), while other parameters were preserved. In the control group, a decrease in ejection fraction (p = 0.001), an increase in left ventricular end-diastolic pressure (p < 0.001), an increase in left ventricular endsystolic pressure (p < 0.001) and an increase in the left atrium anteroposterior diameter (p < 0.001) were detected. While the PWV value, measured oscillometrically and evaluated as a vascular stiffness parameter, increased significantly in the control group (p < 0.001). Conclusion In patients with breast cancer who have received anthracyclines, dexrazoxane protects patients from the negative effects of anthracyclines on arteriosclerosis. Anthracycline atherosclerosis breast cancer dexrazoxane echocardiography INTRODUCTION Breast cancer is the most frequently diagnosed malignancy, with more than two million new cases worldwide each year ( 1 ). Breast cancer death rates are gradually decreasing ( 2 ). This decrease in mortality is due to advances in breast cancer screening and treatment ( 3 ). Possible side effects of the agents used in therapy have become an important health problem with the increase in survival in breast cancer. Agents used in breast cancer treatment affect tumor tissue as well as other organs and tissues. One of the most affected systems is the cardiovascular system. In this context, death from cardiovascular diseases is common in patients receiving chemotherapy ( 4 – 6 ). Anthracyclines are among the main agents used in both neoadjuvant and adjuvant therapy in the treatment of breast cancer. The cardiotoxic effects of anthracyclines have been shown in many studies ( 7 ). Although these effects are dependent on the cumulative dose, they are also seen at low doses in some patients ( 8 ). It occurs by inhibiting the DNA Topoisomerase 2 enzyme, resulting in DNA breaks and the release of free oxygen radicals ( 9 ). Dexrazoxane is an iron chelator that has been used for a long time in the prevention and treatment of cardiotoxicity due to anthracyclines. It is believed that the protective effect of dexrazoxane against cardiotoxicity is due to its ability to chelate the hydrolysis products of iron within myocardial cells, as a result reducing the metal ion and anthracycline complex, leading to a decrease in the formation of superoxide radicals ( 10 ). Diagnosing chemotherapy-induced cardiotoxicity and starting treatment early is vital. Our study is one of the first studies about the effects of anthracyclines on arteriosclerosis and its prevention. MATERIALS AND METHODS 60 patients diagnosed with breast cancer and receiving anthracycline-based chemotherapy, followed in the Ondokuz Mayıs University Medical Oncology clinic between January 2018 and January 2022, were included in our study by scanning their files. It was planned that there would be 30 patients receiving dexrazoxane in the study group and 30 patients not receiving dexrazoxane in the control group. Patients with systemic chronic disease, those who smoked, those who had received chemotherapy before, those with a left ventricular ejection fraction of 50 or less, those with morbid obesity, and those with valvular heart disease were not included in the study. Detailed medical histories of all patients were obtained and physical properties and age were recorded. Our study is a prospective case-control study. Approval dated 13.12.2023 and numbered B.30.2.ODM.0.20.08/631 was received from the Ondokuz Mayıs University Ethics Committee Committee and the study was conducted in accordance with the principles of the Declaration of Helsinki. Transthoracic echocardiographic evaluation: All patients underwent transthoracic echocardiography (TTE) before chemotherapy and 1 month after treatment was completed. Systolic and diastolic diameters of the ascending aorta, left atrium anteroposterior diameter, interventricular septum thickness, left ventricular end-diastolic and end-systolic diameters were measured by TTE. Valve functions were evaluated using colour doppler. Arteriographic evaluation: Arterial stiffness in patients was evaluated before and 1 month after chemotherapy using the validated Mobil-O-Graph 24-hour ABPM NG (Stolberg, Germany) arthriography device. Parameters evaluated in oscillometric measurements performed by this device are systolic and diastolic blood pressure (SBP and DBP), mean arterial pressure (OAP), pulse, central systolic blood pressure (cSBP), central diastolic blood pressure (cDBP) and arterial system wave velocity (PWV). After the contraction of the left ventricle, blood is sent to the ascending aorta, causing the aorta to dilate. Since the aortic wall has an elastic structure, a pulse wave occurs in the artery wall after each beat. This pulse wave consists of three different waveforms: The first wave emitted from the heart during systole (P1), the wave arising from vascular bifurcations and reflected from the distal to the heart during diastole (P2). The last two waveforms can be considered as a single wave because they overlap. The first wave P1 is related to arterial stiffness and the second wave, P2 is related to elastic reflexion of the aortic surface ( 11 ). PWC is the speed of waves occurring in the arterial system. This value is the distance the arterial pulse wave travels divided by the time.( 12 ). It is shown as ‘PWV = d (meters) / t (seconds)’. Increased arterial stiffness means that the speed and PWV of direct and reflected waves increase together. In breast cancer patients, measurements were made on the arm opposite the breast with cancer. Anthracycline administration All patients received neoadjuvant or adjuvant anthracycline treatment at a dose of 50 mg/m2 once a day for 14 days. The cumulative dose ranged from 194 mg to 383 mg at the end of treatment, Dexrazoxane administration : Dexrazoxane was administrated to the study group 30 minutes before doxorubicin infusion, taking into account the 10:1 dexrazoxane: doxorubicin ratio (dexrazoxane 500 mg/m2: doxorubicin 50 mg/m2). Statistical Analysis Research data was collected through the "SPSS (Statistical Package for Social Sciences) for Windows 21.0 (SPSS Inc, Chicago, IL)" program (spss.int.omu.edu.tr-Network License). Descriptive statistics are presented as mean ± standard deviation, frequency distribution and percentage. The suitability of the variables to normal distribution was examined using visual (histogram and probability graphs) and analytical methods (Shapiro-Wilk Test). For variables complying with normal distribution, Student's T Test was applied for statistical significance between two independent groups and Paired Sample T Test was applied for statistical significance between two dependent groups. Statistical significance level was accepted as p < 0.05. Table 1 Demographic Characteristics of the Patients Included in the Study Control Group (n = 30) Study Group (n = 30) Test Stat. P 1 Age 42 (28–57) /27,6 45 (23–58) /33,3 535 0,208 BMI (kg/m²) 26,6 (20,2–34,5) /31,5 26 (17,3–34,5) /29,4 419 0,647 Cigarette 0 0 N/A N/A Alcohol 0 0 N/A N/A Hypertension 0 0 N/A N/A Diabetes 0 0 N/A N/A Hyperlipidemia 0 0 N/A N/A Coronary Artery Disease 0 0 N/A N/A Fasting Blood Sugar (mg/dL) 94 (69–132) /28,3 95 (79–125) /32,6 514 0,343 Creatinine (mg/dL) 0,7 (0,5 − 0,9) /32,2 0,6 (0,5 − 1) /28,7 446 0,446 AST (U/L) 15,3 (10,3–28) /31,5 15,5 ( 11 , 3 – 23 , 9 ) /29,4 417,5 0,631 ALT (U/L) 15 (6,8–43) /33,2 11,6 (5,1–41,6) /27,5 367,5 0,223 Hemoglobin (g/dL) 12,9 ( 10 , 1 – 15 , 6 ) /30,4 13,1 ( 9 , 5 – 14 , 7 ) /30,5 452,5 0,97 Histological Type Invasive Ductal Carsinoma, n (%) 29 (%96,7) 27 (%90) 480 0,305 Invasive Lobular Carcinoma, n (%) 1 (%3,3) 3 (%10) Invasive Tumor Diameter, mm 28 (15–80) 31 (7–70) 474 0,723 Tumor Surgery No Surgical Procedure was Performed, n (%) 8 (%26,7) 4 (%13,3) 544 0,105 Radical Mastectomy, n (%) 6 (%20) 4 (%13,3) Breast-Conserving Surgery, n (%) 16 (%53,3) 22 (%73,3) Radiotherapy Did not receive, n (%) 15 (%50) 16 (%53,3) 435 0,798 Received, n (%) 15 (%50) 14 (%46,7) Hormone Therapy Did not receive, n (%) 15 (%50) 16 (%53,3) 435 0,798 Received, n (%) 15 (%50) 14 (%46,7) 1Mann-Whitney U Test, Median (Min-Max), Mean Rank. RESULTS ​The demographic characteristics of the patients are shown in Table 1 . The average age of the study group was 45 (23–58) and the average age of the control group was 42 (28–57) (p = 0.208). No significant difference was found in terms of BMI in both groups (p = 0.508). 27 patients (90%) in the study group were diagnosed with invasive ductal carcinoma and 3 patients (10%) with invasive lobular carcinoma. About the control group, 29 patients (96.7%) were diagnosed with invasive ductal carcinoma and 1 (3.7%) patient was diagnosed with invasive lobular carcinoma. The invasive tumor diameter of the study group was measured as 31 mm, and the tumor diameter of the control group was measured as 28 mm (p = 0.723). 14 patients (46%) in the study group and 15 patients (50%) in the control group received radiotherapy (p = 0.798). 14 women (46%) in the study group and 15 women (50%) in the other group received hormone therapy. All patients received the doxorubicin protocol. No differences were detected according to the groups when the patients included in the study were examined in terms of demographic features and baseline laboratory parameters (Table 1 ). When the patients were examined in terms of cancer types, grades and tumor diameter, no statistically significant difference was detected between both groups. Additionally, no difference was detected in the treatment regimens received after diagnosis (Table 1 ). Echocardiographic findings: In echocardiographic measurements, while there was an increase in left ventricular end-diastolic diameter (LVEDD) in the study group (p = 0.008), there was no significant change in other parameters. About the control group, there was a decrease in ejection fraction (LVEF) (p = 0.001), an increase in left ventricular end-diastolic diameter (LVEDD) (p < 0.001), an increase in left ventricular end-systolic diameter (LVESD) (p < 0.001) and increase in left atrium anteroposterior diameter (p < 0.001) (Table 2 ). Table 2 Evaluation of Echocardiographic Parameters According to Study Groups and Before/After Treatment Control Group (n = 30) Study Group (n = 30) Test Stat. p² LVEF (%) Before Treatment 61,6 ± 3,39 61,2 ± 4,11 0,480 0,633 After Treatment 59,4 ± 4,3 60,5 ± 4,03 -0,991 0,326 p ¹ 0,001 0,070 LVEDD (mm) Before Treatment 42,2 ± 4,06 44 ± 4,59 -1,580 0,119 After Treatment 44,3 ± 4,76 44,6 ± 4,48 -0,223 0,824 p ¹ < 0,001 0,008 LVESD (mm) Before Treatment 26 ± 3,62 23,9 ± 2,78 2,481 0,016 After Treatment 28,2 ± 4,44 24,2 ± 2,93 4,048 < 0,001 p ¹ < 0,001 0,223 PW (mm) Before Treatment 9,7 ± 1,32 9,4 ± 1,77 0,577 0,566 After Treatment 10 ± 1,44 9,5 ± 1,93 1,064 0,292 p ¹ 0,057 0,415 LA (mm) Before Treatment 29,3 ± 3,34 29,4 ± 3,64 -0,148 0,883 After Treatment 30,5 ± 3,33 29,8 ± 3,42 0,842 0,403 p ¹ < 0,001 0,086 1: Paired Samples T Test/Wilcoxon; 2: Independent- Samples T Test When both echocardiographic parameters were evaluated in the study population, LVEF (p = 0.001), LVEDD (p < 0.001), LVESD (p < 0.001) and LA size (p < 0.001) increased statistically significantly in the control group compared to before treatment. In the dextrazoxane group, only LVEDD increased significantly after treatment compared to before (p < 0.001). When the parameters were compared between both groups, only LVESD was found to be statistically significantly higher in the control group in the post-treatment period. Oscillometric measurements: There was no significant change in all parameters. PWC value was found to be significantly increased in the control group (p < 0.001). No significant changes were detected in other parameters (Table 3 ). Table 3 Evaluation of Oscillometric Measurements According to Study Groups and Before/After Treatment Control Group (n = 30) Study Group (n = 30) Test Stat. P 2 PWV (m/sn) Before Treatment 6,2 ± 0,8 7,3 ± 1,7 -3,06 0,003 After Treatment 6,5 ± 0,8 7,2 ± 1,6 -2,36 0,022 P 1 < 0,001 0,766 SBP (mmHg) Before Treatment 121,1 ± 14,9 124,2 ± 12,6 -0,87 0,387 After Treatment 125,3 ± 16,8 122,6 ± 15,3 0,64 0,523 P 1 0,043 0,975 DBP (mmHg) Before Treatment 77,5 ± 11,8 81,2 ± 8,5 -1,42 0,160 After Treatment 79,6 ± 13,7 81,5 ± 10,3 -0,03 0,975 P 1 0,290 0,484 Pulse (beat/min) Before Treatment 86,6 ± 17,8 83,2 ± 9,4 0,92 0,361 After Treatment 88,4 ± 14,4 86,8 ± 8,2 0,53 0,599 P 1 0,422 0,872 OAP (mmHg) Before Treatment 97,5 ± 12,7 100,6 ± 9,8 -1,03 0,305 After Treatment 100,5 ± 14,6 99,5 ± 12,6 0,27 0,785 P 1 0,115 0,062 sSBP (mmHg) Before Treatment 111,2 ± 12,5 115,8 ± 13,8 -1,35 0,182 After Treatment 114,5 ± 16,2 114,3 ± 16,6 0,06 0,956 P 1 0,105 0,595 sDBP (mmHg) Before Treatment 79 ± 11,9 82 ± 8,1 -1,14 0,260 After Treatment 81,3 ± 13,8 81,4 ± 10,1 -0,03 0,975 P 1 0,262 0,527 1: Paired Samples T Test; 2: Independent- Samples T Test In the study population, the PWV value was found to be statistically different between the two groups, being higher in the dexrazoxane group (p = 0.003). This difference continues after treatment (p = 0.022). While PWV increased significantly in the control group in the post-treatment period compared to the pre-treatment period (p < 0.001), it tended to decrease in a non-statistically significant manner in the dextrazoxane group. (7.3 ± 1.7 before treatment and 7.2 ± 1.6 after treatment, p = 0.766). In other parameters measured oscillometrically, no significant difference was detected before and after treatment (Table 3 ). DISCUSSION In this study including breast cancer patients, we evaluated the effects of this chemotherapy drug on arteriosclerosis, as well as the cardiotoxic effects of anthracyclines. In oscillometric measurements, it was determined that anthracyclines also had negative effects on arteriosclerosis. In this study, we also found that dexrazoxane protects against the cardiotoxic effects of anthracyclines as well as their negative effects on arteriosclerosis. Although echocardiography is the most commonly used diagnostic method for diagnosing cardiotoxicity, it is not a sufficient method on its own. It has been shown in various studies that early diagnosis and treatment after cardiotoxic chemotherapeutic agents stop the progression of damage and accelerate recovery ( 13 ). It is essential to detect cardiotoxicity and start treatment early. Studies have shown that arterial stiffness is an independent risk factor for the development of cardiovascular disease ( 14 ). Various studies have shown that decreased elastic capacity of the major arteries to resist pulse pressure and increased vascular stiffness are related with future cardiovascular events.( 15 – 16 ). A 1 m/s increase in aortic pulse wave velocity has been found to be associated with a 15% increase occurrence of cardiovascular adverse events ( 17 ). Methods used to evaluate arterial stiffness include transthoracic echocardiography, magnetic resonance angiography, catheter angiography, intrathoracic surgical approach and arteriographic methods. The efficacy and safety of the arteriography device we used to measure vascular stiffness in our study has been demonstrated in comparative studies with different methods such as the SphygmoCor system ( 18 ). Comparison of central BP values measured by the two vehicles showed a statistically significant linear correlation (p < 0.0001). The mean difference between methods for central SBP estimation was 0.50 mmHg. Bland and Altman analyzes showed that the mean differences (95% CI) between repeated measurements were 1.89 (0.42–3.36) mmHg and 1.36 (-0.16-2.83 mmHg). Therefore, none of these differences were significantly different from 0 ( 18 ). The use of anthracyclines is limited due to dose-dependent cardiotoxicity. It is not clear by what mechanism anthracyclines cause cardiotoxicity. Clinically, cardiotoxicity is defined by the symptoms and signs of congestive heart failure (CHF). Various approaches have been taken to reduce the toxic effects on the heart, such as limiting anthracycline doses, using dexrazoxane, developing anthracycline analogs, and replacing intravenous rapid infusion with slow infusion ( 19 ). A study of breast cancer patients reported a statistically significantly lower response rate in women treated with dexrazoxane than in untreated patients( 20 ). However, in this study, time to progression and overall survival were not different between groups. None of the three recently published studies found that dexrazoxane use affected the efficacy of chemotherapy ( 21 – 23 ). In the P9404 study, event-free survival did not differ between the groups receiving and not receiving dexrazoxane (p = 0.86) ( 21 ). In their study on 29 breast cancer patients and 12 healthy volunteers treated with cardiotoxic chemotherapeutics, Grover and colleagues evaluated the patients using magnetic resonance images before and after treatment ( 24 ). As a result of the evaluation, they found a significant increase in PWV in the study group. According to another study conducted in patients receiving anthracycline chemotherapy, PWV was observed to increase compared to pre-treatment values ​​when evaluated six months after therapy ( 25 ). In our study, while PWV values were similar in both groups before treatment, PWV value increased significantly in the study group after treatment. In a another study conducted on 35 female breast cancer patients and scheduled to receive anthracycline therapy, echocardiographic evaluation of the patients were made before treatment and six months after treatment. While no significant change was observed in systolic functions, diastolic dysfunction was observed and it was reported that this was due to the increase in load and stress resulting from increased vascular stiffness ( 26 ). In our study, while deterioration in diastolic functions was detected in the group that did not receive dexrazoxane, no significant change was observed in the group that received dexrazoxane. The limitations of our study are that it is single-center, the number of patients is small and the patients do not have long-term results. In conclusion, our study is important because it shows that dextrazoxane protects against the risk of cardiotoxicity in breast cancer patients receiving anthracycline-based treatment, while also showing its positive effect on the PWV value, which is used as an indicator of arteriosclerosis and that, to the best of our knowledge, it is one of the first studies on this subject. Declarations Disclosures Human Ethics and Consent to Participate declarations are available. Ethics Committee Approval: Ethic committee approval was obtained from Ondokuz Mayıs University Ethics Committee. Conflict of Interest: None declared. Authorship Contributions: Concept – D.I.B.and R.T; Design – D.I.B.; Supervision – G.D.; Materials – R.T.; Data collection &/or processing – R.T.; Analysis and/or interpretation – D.I.B.; Literature serach – D.I.B.,RT.; Writing – D.I.B.; Critical review – G.D. Funding: There is no funding. Data availability statement: The datasets used and/or analysed during the current study available from the corresponding author on reasonable request. References GLOBOCAN. 2020: New global cancer data. https://www.uicc.org/news/globocan-2020-new-global-cancer-data (Accessed on November 24, 2021). Kohler BA, Sherman RL, Howlader N, Jemal A, Ryerson AB, Henry KA et al. 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Low to moderate dose anthracycline-based chemotherapy is associated with early noninvasive imaging evidence of subclinical cardiovascular disease. JACC Cardiovasc Imaging. 2013;6:877–85. Mizia-Stec K, Gościńska A, Mizia M, Haberka M, Chmiel A, Poborski W, Gąsior Z. Anthracycline chemotherapy impairs the structure and diastolic function of the left ventricle and induces negative arterial remodelling. Kardiol Pol. 2013;71:681–90. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6990789","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":488133421,"identity":"77d4f50b-5548-400f-a6fd-0508b487f67b","order_by":0,"name":"Demet Isik Bayraktar","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8klEQVRIiWNgGAWjYDCCAyCCDYh5mA8++ABisxOj5QBYC1uy4QyQFmbitfCYSfOARAhp4Tvenfj4Q5lNvsGZYwnSNr+2yfMxMzB++JiDW4vkmbObDQ6cS7PccLb5gHFu323DNmYGZsmZ23BrMbiRu03iYNthA4PzbAnJuT23GYFa2Jh58Wm5/3b7D4gWHoPDlj237QlruQGUBWs522PYzPDjdiJBLZJncjdLnDmXZiB55lgyY2/D7eQ2ZsZmvH7hO35244eKMhsDvjPJx3/8+HPbdn5788EPH/FoQQWMbWCygVj1IPCHFMWjYBSMglEwUgAAD2RaYkmyM9kAAAAASUVORK5CYII=","orcid":"","institution":"Amasya University","correspondingAuthor":true,"prefix":"","firstName":"Demet","middleName":"Isik","lastName":"Bayraktar","suffix":""},{"id":488133422,"identity":"ddc4b538-12ed-4084-bea5-d080f0210871","order_by":1,"name":"Recep Turkel","email":"","orcid":"","institution":"Ondokuz Mayıs University","correspondingAuthor":false,"prefix":"","firstName":"Recep","middleName":"","lastName":"Turkel","suffix":""},{"id":488133426,"identity":"2998bdc8-5171-4614-bd15-8a8bce35605f","order_by":2,"name":"Guzin Demirag","email":"","orcid":"","institution":"Ondokuz Mayıs University","correspondingAuthor":false,"prefix":"","firstName":"Guzin","middleName":"","lastName":"Demirag","suffix":""}],"badges":[],"createdAt":"2025-06-27 10:38:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6990789/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6990789/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":94597786,"identity":"886cf88d-6c6f-42e6-8fcf-b6271c04417b","added_by":"auto","created_at":"2025-10-28 18:49:11","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":764327,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6990789/v1/cfefaeeb-a5d7-458e-9242-9abe68cf8bde.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effects of Anthracyclines on Atherosclerosis in Patients with Breast Cancer and Protective Effect of Dexrazoxane","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eBreast cancer is the most frequently diagnosed malignancy, with more than two million new cases worldwide each year (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Breast cancer death rates are gradually decreasing (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). This decrease in mortality is due to advances in breast cancer screening and treatment (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Possible side effects of the agents used in therapy have become an important health problem with the increase in survival in breast cancer. Agents used in breast cancer treatment affect tumor tissue as well as other organs and tissues. One of the most affected systems is the cardiovascular system. In this context, death from cardiovascular diseases is common in patients receiving chemotherapy (\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Anthracyclines are among the main agents used in both neoadjuvant and adjuvant therapy in the treatment of breast cancer. The cardiotoxic effects of anthracyclines have been shown in many studies (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Although these effects are dependent on the cumulative dose, they are also seen at low doses in some patients (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). It occurs by inhibiting the DNA Topoisomerase 2 enzyme, resulting in DNA breaks and the release of free oxygen radicals (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Dexrazoxane is an iron chelator that has been used for a long time in the prevention and treatment of cardiotoxicity due to anthracyclines. It is believed that the protective effect of dexrazoxane against cardiotoxicity is due to its ability to chelate the hydrolysis products of iron within myocardial cells, as a result reducing the metal ion and anthracycline complex, leading to a decrease in the formation of superoxide radicals (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Diagnosing chemotherapy-induced cardiotoxicity and starting treatment early is vital. Our study is one of the first studies about the effects of anthracyclines on arteriosclerosis and its prevention.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cp\u003e 60 patients diagnosed with breast cancer and receiving anthracycline-based chemotherapy, followed in the Ondokuz Mayıs University Medical Oncology clinic between January 2018 and January 2022, were included in our study by scanning their files. It was planned that there would be 30 patients receiving dexrazoxane in the study group and 30 patients not receiving dexrazoxane in the control group. Patients with systemic chronic disease, those who smoked, those who had received chemotherapy before, those with a left ventricular ejection fraction of 50 or less, those with morbid obesity, and those with valvular heart disease were not included in the study. Detailed medical histories of all patients were obtained and physical properties and age were recorded. Our study is a prospective case-control study. Approval dated 13.12.2023 and numbered B.30.2.ODM.0.20.08/631 was received from the Ondokuz Mayıs University Ethics Committee Committee and the study was conducted in accordance with the principles of the Declaration of Helsinki.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eTransthoracic echocardiographic evaluation:\u003c/h2\u003e\u003cp\u003eAll patients underwent transthoracic echocardiography (TTE) before chemotherapy and 1 month after treatment was completed. Systolic and diastolic diameters of the ascending aorta, left atrium anteroposterior diameter, interventricular septum thickness, left ventricular end-diastolic and end-systolic diameters were measured by TTE. Valve functions were evaluated using colour doppler.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eArteriographic evaluation:\u003c/h3\u003e\n\u003cp\u003eArterial stiffness in patients was evaluated before and 1 month after chemotherapy using the validated Mobil-O-Graph 24-hour ABPM NG (Stolberg, Germany) arthriography device. Parameters evaluated in oscillometric measurements performed by this device are systolic and diastolic blood pressure (SBP and DBP), mean arterial pressure (OAP), pulse, central systolic blood pressure (cSBP), central diastolic blood pressure (cDBP) and arterial system wave velocity (PWV). After the contraction of the left ventricle, blood is sent to the ascending aorta, causing the aorta to dilate. Since the aortic wall has an elastic structure, a pulse wave occurs in the artery wall after each beat. This pulse wave consists of three different waveforms: The first wave emitted from the heart during systole (P1), the wave arising from vascular bifurcations and reflected from the distal to the heart during diastole (P2). The last two waveforms can be considered as a single wave because they overlap. The first wave P1 is related to arterial stiffness and the second wave, P2 is related to elastic reflexion of the aortic surface (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e\u003cp\u003ePWC is the speed of waves occurring in the arterial system. This value is the distance the arterial pulse wave travels divided by the time.(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). It is shown as \u0026lsquo;PWV\u0026thinsp;=\u0026thinsp;d (meters) / t (seconds)\u0026rsquo;.\u003c/p\u003e\u003cp\u003eIncreased arterial stiffness means that the speed and PWV of direct and reflected waves increase together. In breast cancer patients, measurements were made on the arm opposite the breast with cancer.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eAnthracycline administration\u003c/strong\u003e\u003cp\u003eAll patients received neoadjuvant or adjuvant anthracycline treatment at a dose of 50 mg/m2 once a day for 14 days. The cumulative dose ranged from 194 mg to 383 mg at the end of treatment,\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eDexrazoxane administration\u003c/b\u003e: Dexrazoxane was administrated to the study group 30 minutes before doxorubicin infusion, taking into account the 10:1 dexrazoxane: doxorubicin ratio (dexrazoxane 500 mg/m2: doxorubicin 50 mg/m2).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003cp\u003eResearch data was collected through the \"SPSS (Statistical Package for Social Sciences) for Windows 21.0 (SPSS Inc, Chicago, IL)\" program (spss.int.omu.edu.tr-Network License). Descriptive statistics are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, frequency distribution and percentage. The suitability of the variables to normal distribution was examined using visual (histogram and probability graphs) and analytical methods (Shapiro-Wilk Test). For variables complying with normal distribution, Student's T Test was applied for statistical significance between two independent groups and Paired Sample T Test was applied for statistical significance between two dependent groups. Statistical significance level was accepted as p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDemographic Characteristics of the Patients Included in the Study\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eControl Group (n\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eStudy Group (n\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTest Stat.\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e42 (28\u0026ndash;57) /27,6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e45 (23\u0026ndash;58) /33,3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e535\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0,208\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI (kg/m\u0026sup2;)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26,6 (20,2\u0026ndash;34,5) /31,5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e26 (17,3\u0026ndash;34,5) /29,4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e419\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0,647\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCigarette\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlcohol\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHyperlipidemia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCoronary Artery Disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFasting Blood Sugar (mg/dL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e94 (69\u0026ndash;132) /28,3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e95 (79\u0026ndash;125) /32,6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e514\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0,343\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCreatinine (mg/dL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0,7 (0,5\u0026thinsp;\u0026minus;\u0026thinsp;0,9) /32,2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0,6 (0,5\u0026thinsp;\u0026minus;\u0026thinsp;1) /28,7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e446\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0,446\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAST (U/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15,3 (10,3\u0026ndash;28) /31,5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15,5 (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan additionalcitationids=\"CR4 CR5 CR6 CR7 CR8 CR9 CR10 CR11 CR12 CR13 CR14 CR15 CR16 CR17 CR18 CR19 CR20 CR21 CR22\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) /29,4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e417,5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0,631\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eALT (U/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15 (6,8\u0026ndash;43) /33,2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11,6 (5,1\u0026ndash;41,6) /27,5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e367,5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0,223\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHemoglobin (g/dL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12,9 (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan additionalcitationids=\"CR2 CR3 CR4 CR5 CR6 CR7 CR8 CR9 CR10 CR11 CR12 CR13 CR14\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) /30,4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13,1 (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan additionalcitationids=\"CR6 CR7 CR8 CR9 CR10 CR11 CR12 CR13\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) /30,5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e452,5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0,97\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHistological Type\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInvasive Ductal Carsinoma, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e29 (%96,7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27 (%90)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e480\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0,305\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInvasive Lobular Carcinoma, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (%3,3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (%10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInvasive Tumor Diameter, mm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28 (15\u0026ndash;80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31 (7\u0026ndash;70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e474\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0,723\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTumor Surgery\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo Surgical Procedure was Performed, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (%26,7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (%13,3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e544\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0,105\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRadical Mastectomy, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (%20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (%13,3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBreast-Conserving Surgery, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16 (%53,3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22 (%73,3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRadiotherapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDid not receive, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15 (%50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16 (%53,3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e435\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0,798\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eReceived, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15 (%50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14 (%46,7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHormone Therapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDid not receive, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15 (%50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16 (%53,3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e435\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0,798\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eReceived, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15 (%50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14 (%46,7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e1Mann-Whitney U Test, Median (Min-Max), Mean Rank.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003e​The demographic characteristics of the patients are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The average age of the study group was 45 (23\u0026ndash;58) and the average age of the control group was 42 (28\u0026ndash;57) (p\u0026thinsp;=\u0026thinsp;0.208). No significant difference was found in terms of BMI in both groups (p\u0026thinsp;=\u0026thinsp;0.508). 27 patients (90%) in the study group were diagnosed with invasive ductal carcinoma and 3 patients (10%) with invasive lobular carcinoma. About the control group, 29 patients (96.7%) were diagnosed with invasive ductal carcinoma and 1 (3.7%) patient was diagnosed with invasive lobular carcinoma. The invasive tumor diameter of the study group was measured as 31 mm, and the tumor diameter of the control group was measured as 28 mm (p\u0026thinsp;=\u0026thinsp;0.723). 14 patients (46%) in the study group and 15 patients (50%) in the control group received radiotherapy (p\u0026thinsp;=\u0026thinsp;0.798). 14 women (46%) in the study group and 15 women (50%) in the other group received hormone therapy.\u003c/p\u003e\u003cp\u003eAll patients received the doxorubicin protocol. No differences were detected according to the groups when the patients included in the study were examined in terms of demographic features and baseline laboratory parameters (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eWhen the patients were examined in terms of cancer types, grades and tumor diameter, no statistically significant difference was detected between both groups. Additionally, no difference was detected in the treatment regimens received after diagnosis (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003ch3\u003eEchocardiographic findings:\u003c/h3\u003e\n\u003cp\u003eIn echocardiographic measurements, while there was an increase in left ventricular end-diastolic diameter (LVEDD) in the study group (p\u0026thinsp;=\u0026thinsp;0.008), there was no significant change in other parameters. About the control group, there was a decrease in ejection fraction (LVEF) (p\u0026thinsp;=\u0026thinsp;0.001), an increase in left ventricular end-diastolic diameter (LVEDD) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), an increase in left ventricular end-systolic diameter (LVESD) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and increase in left atrium anteroposterior diameter (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eEvaluation of Echocardiographic Parameters According to Study Groups and Before/After Treatment\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eControl Group (n\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eStudy Group (n\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTest Stat.\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003ep\u0026sup2;\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eLVEF (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBefore Treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e61,6\u0026thinsp;\u0026plusmn;\u0026thinsp;3,39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e61,2\u0026thinsp;\u0026plusmn;\u0026thinsp;4,11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0,480\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0,633\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAfter Treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e59,4\u0026thinsp;\u0026plusmn;\u0026thinsp;4,3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e60,5\u0026thinsp;\u0026plusmn;\u0026thinsp;4,03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-0,991\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0,326\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026sup1;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e0,001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0,070\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eLVEDD (mm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBefore Treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e42,2\u0026thinsp;\u0026plusmn;\u0026thinsp;4,06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e44\u0026thinsp;\u0026plusmn;\u0026thinsp;4,59\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-1,580\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0,119\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAfter Treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e44,3\u0026thinsp;\u0026plusmn;\u0026thinsp;4,76\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e44,6\u0026thinsp;\u0026plusmn;\u0026thinsp;4,48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-0,223\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0,824\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026sup1;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0,001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,008\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eLVESD (mm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBefore Treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e26\u0026thinsp;\u0026plusmn;\u0026thinsp;3,62\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e23,9\u0026thinsp;\u0026plusmn;\u0026thinsp;2,78\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2,481\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0,016\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAfter Treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28,2\u0026thinsp;\u0026plusmn;\u0026thinsp;4,44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e24,2\u0026thinsp;\u0026plusmn;\u0026thinsp;2,93\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4,048\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0,001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026sup1;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0,001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0,223\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003ePW (mm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBefore Treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9,7\u0026thinsp;\u0026plusmn;\u0026thinsp;1,32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9,4\u0026thinsp;\u0026plusmn;\u0026thinsp;1,77\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0,577\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0,566\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAfter Treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10\u0026thinsp;\u0026plusmn;\u0026thinsp;1,44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9,5\u0026thinsp;\u0026plusmn;\u0026thinsp;1,93\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1,064\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0,292\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026sup1;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0,057\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0,415\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eLA (mm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBefore Treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e29,3\u0026thinsp;\u0026plusmn;\u0026thinsp;3,34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e29,4\u0026thinsp;\u0026plusmn;\u0026thinsp;3,64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-0,148\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0,883\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAfter Treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e30,5\u0026thinsp;\u0026plusmn;\u0026thinsp;3,33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e29,8\u0026thinsp;\u0026plusmn;\u0026thinsp;3,42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0,842\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0,403\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026sup1;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0,001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0,086\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003e1: Paired Samples T Test/Wilcoxon; 2: Independent- Samples T Test\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eWhen both echocardiographic parameters were evaluated in the study population, LVEF (p\u0026thinsp;=\u0026thinsp;0.001), LVEDD (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), LVESD (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and LA size (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) increased statistically significantly in the control group compared to before treatment. In the dextrazoxane group, only LVEDD increased significantly after treatment compared to before (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). When the parameters were compared between both groups, only LVESD was found to be statistically significantly higher in the control group in the post-treatment period.\u003c/p\u003e\n\u003ch3\u003eOscillometric measurements:\u003c/h3\u003e\n\u003cp\u003eThere was no significant change in all parameters. PWC value was found to be significantly increased in the control group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). No significant changes were detected in other parameters (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eEvaluation of Oscillometric Measurements According to Study Groups and Before/After Treatment\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eControl Group (n\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eStudy Group (n\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTest Stat.\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eP\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003ePWV (m/sn)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBefore Treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6,2\u0026thinsp;\u0026plusmn;\u0026thinsp;0,8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7,3\u0026thinsp;\u0026plusmn;\u0026thinsp;1,7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-3,06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e0,003\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAfter Treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6,5\u0026thinsp;\u0026plusmn;\u0026thinsp;0,8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7,2\u0026thinsp;\u0026plusmn;\u0026thinsp;1,6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-2,36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e0,022\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0,001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003e0,766\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eSBP (mmHg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBefore Treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e121,1\u0026thinsp;\u0026plusmn;\u0026thinsp;14,9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e124,2\u0026thinsp;\u0026plusmn;\u0026thinsp;12,6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-0,87\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0,387\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAfter Treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e125,3\u0026thinsp;\u0026plusmn;\u0026thinsp;16,8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e122,6\u0026thinsp;\u0026plusmn;\u0026thinsp;15,3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0,64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0,523\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003e0,043\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003e0,975\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eDBP (mmHg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBefore Treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e77,5\u0026thinsp;\u0026plusmn;\u0026thinsp;11,8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e81,2\u0026thinsp;\u0026plusmn;\u0026thinsp;8,5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-1,42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0,160\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAfter Treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e79,6\u0026thinsp;\u0026plusmn;\u0026thinsp;13,7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e81,5\u0026thinsp;\u0026plusmn;\u0026thinsp;10,3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-0,03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0,975\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003e0,290\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003e0,484\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003ePulse (beat/min)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBefore Treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e86,6\u0026thinsp;\u0026plusmn;\u0026thinsp;17,8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e83,2\u0026thinsp;\u0026plusmn;\u0026thinsp;9,4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0,92\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0,361\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAfter Treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e88,4\u0026thinsp;\u0026plusmn;\u0026thinsp;14,4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e86,8\u0026thinsp;\u0026plusmn;\u0026thinsp;8,2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0,53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0,599\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003e0,422\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003e0,872\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eOAP (mmHg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBefore Treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e97,5\u0026thinsp;\u0026plusmn;\u0026thinsp;12,7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e100,6\u0026thinsp;\u0026plusmn;\u0026thinsp;9,8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-1,03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0,305\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAfter Treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e100,5\u0026thinsp;\u0026plusmn;\u0026thinsp;14,6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e99,5\u0026thinsp;\u0026plusmn;\u0026thinsp;12,6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0,27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0,785\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003e0,115\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003e0,062\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003esSBP (mmHg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBefore Treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e111,2\u0026thinsp;\u0026plusmn;\u0026thinsp;12,5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e115,8\u0026thinsp;\u0026plusmn;\u0026thinsp;13,8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-1,35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0,182\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAfter Treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e114,5\u0026thinsp;\u0026plusmn;\u0026thinsp;16,2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e114,3\u0026thinsp;\u0026plusmn;\u0026thinsp;16,6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0,06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0,956\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003e0,105\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003e0,595\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003esDBP (mmHg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBefore Treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e79\u0026thinsp;\u0026plusmn;\u0026thinsp;11,9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e82\u0026thinsp;\u0026plusmn;\u0026thinsp;8,1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-1,14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0,260\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAfter Treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e81,3\u0026thinsp;\u0026plusmn;\u0026thinsp;13,8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e81,4\u0026thinsp;\u0026plusmn;\u0026thinsp;10,1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-0,03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0,975\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003e0,262\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003e0,527\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003e1: Paired Samples T Test; 2: Independent- Samples T Test\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eIn the study population, the PWV value was found to be statistically different between the two groups, being higher in the dexrazoxane group (p\u0026thinsp;=\u0026thinsp;0.003). This difference continues after treatment (p\u0026thinsp;=\u0026thinsp;0.022). While PWV increased significantly in the control group in the post-treatment period compared to the pre-treatment period (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), it tended to decrease in a non-statistically significant manner in the dextrazoxane group. (7.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7 before treatment and 7.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6 after treatment, p\u0026thinsp;=\u0026thinsp;0.766). In other parameters measured oscillometrically, no significant difference was detected before and after treatment (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIn this study including breast cancer patients, we evaluated the effects of this chemotherapy drug on arteriosclerosis, as well as the cardiotoxic effects of anthracyclines. In oscillometric measurements, it was determined that anthracyclines also had negative effects on arteriosclerosis. In this study, we also found that dexrazoxane protects against the cardiotoxic effects of anthracyclines as well as their negative effects on arteriosclerosis.\u003c/p\u003e\u003cp\u003eAlthough echocardiography is the most commonly used diagnostic method for diagnosing cardiotoxicity, it is not a sufficient method on its own. It has been shown in various studies that early diagnosis and treatment after cardiotoxic chemotherapeutic agents stop the progression of damage and accelerate recovery (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). It is essential to detect cardiotoxicity and start treatment early. Studies have shown that arterial stiffness is an independent risk factor for the development of cardiovascular disease (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Various studies have shown that decreased elastic capacity of the major arteries to resist pulse pressure and increased vascular stiffness are related with future cardiovascular events.(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). A 1 m/s increase in aortic pulse wave velocity has been found to be associated with a 15% increase occurrence of cardiovascular adverse events (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eMethods used to evaluate arterial stiffness include transthoracic echocardiography, magnetic resonance angiography, catheter angiography, intrathoracic surgical approach and arteriographic methods. The efficacy and safety of the arteriography device we used to measure vascular stiffness in our study has been demonstrated in comparative studies with different methods such as the SphygmoCor system (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Comparison of central BP values measured by the two vehicles showed a statistically significant linear correlation (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). The mean difference between methods for central SBP estimation was 0.50 mmHg. Bland and Altman analyzes showed that the mean differences (95% CI) between repeated measurements were 1.89 (0.42\u0026ndash;3.36) mmHg and 1.36 (-0.16-2.83 mmHg). Therefore, none of these differences were significantly different from 0 (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe use of anthracyclines is limited due to dose-dependent cardiotoxicity. It is not clear by what mechanism anthracyclines cause cardiotoxicity. Clinically, cardiotoxicity is defined by the symptoms and signs of congestive heart failure (CHF). Various approaches have been taken to reduce the toxic effects on the heart, such as limiting anthracycline doses, using dexrazoxane, developing anthracycline analogs, and replacing intravenous rapid infusion with slow infusion (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eA study of breast cancer patients reported a statistically significantly lower response rate in women treated with dexrazoxane than in untreated patients(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). However, in this study, time to progression and overall survival were not different between groups. None of the three recently published studies found that dexrazoxane use affected the efficacy of chemotherapy (\u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). In the P9404 study, event-free survival did not differ between the groups receiving and not receiving dexrazoxane (p\u0026thinsp;=\u0026thinsp;0.86) (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIn their study on 29 breast cancer patients and 12 healthy volunteers treated with cardiotoxic chemotherapeutics, Grover and colleagues evaluated the patients using magnetic resonance images before and after treatment (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). As a result of the evaluation, they found a significant increase in PWV in the study group. According to another study conducted in patients receiving anthracycline chemotherapy, PWV was observed to increase compared to pre-treatment values ​​when evaluated six months after therapy (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). In our study, while PWV values were similar in both groups before treatment, PWV value increased significantly in the study group after treatment.\u003c/p\u003e\u003cp\u003eIn a another study conducted on 35 female breast cancer patients and scheduled to receive anthracycline therapy, echocardiographic evaluation of the patients were made before treatment and six months after treatment. While no significant change was observed in systolic functions, diastolic dysfunction was observed and it was reported that this was due to the increase in load and stress resulting from increased vascular stiffness (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). In our study, while deterioration in diastolic functions was detected in the group that did not receive dexrazoxane, no significant change was observed in the group that received dexrazoxane.\u003c/p\u003e\u003cp\u003eThe limitations of our study are that it is single-center, the number of patients is small and the patients do not have long-term results.\u003c/p\u003e\u003cp\u003eIn conclusion, our study is important because it shows that dextrazoxane protects against the risk of cardiotoxicity in breast cancer patients receiving anthracycline-based treatment, while also showing its positive effect on the PWV value, which is used as an indicator of arteriosclerosis and that, to the best of our knowledge, it is one of the first studies on this subject.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eDisclosures\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHuman Ethics and Consent to Participate declarations are available. Ethics Committee Approval: Ethic committee approval was obtained from Ondokuz Mayıs University Ethics Committee.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest:\u0026nbsp;\u003c/strong\u003eNone declared.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthorship Contributions:\u003c/strong\u003e Concept – D.I.B.and R.T; Design – D.I.B.; Supervision – G.D.; Materials – R.T.; Data collection \u0026amp;/or processing – R.T.; Analysis and/or interpretation – D.I.B.; Literature serach – D.I.B.,RT.; Writing – D.I.B.; Critical review – G.D.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e There is no funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement:\u0026nbsp;\u003c/strong\u003eThe datasets used and/or analysed during the current study available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGLOBOCAN. 2020: New global cancer data. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.uicc.org/news/globocan-2020-new-global-cancer-data\u003c/span\u003e\u003cspan address=\"https://www.uicc.org/news/globocan-2020-new-global-cancer-data\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (Accessed on November 24, 2021).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKohler BA, Sherman RL, Howlader N, Jemal A, Ryerson AB, Henry KA et al. 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J Clin Oncol. 2015;33(24):2639\u0026ndash;45. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1200/JCO.2014.59.4473\u003c/span\u003e\u003cspan address=\"10.1200/JCO.2014.59.4473\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2015 May 26. PMID: 26014292; PMCID: PMC4534526.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLipshultz SE, Scully RE, Lipsitz SR, Sallan SE, Silverman LB, Miller TL, et al. Assessment of dexrazoxane as a cardioprotectant in doxorubicin-treated children with high-risk acute lymphoblastic leukaemia: long-term follow-up of a prospective, randomised, multicentre trial. Lancet Oncol. 2010;11(10):950\u0026ndash;61. Epub 2010 Sep 16. PMID: 20850381; PMCID: PMC3756093.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGrover S, Lou PW, Bradbrook C, Cheong K, Kotasek D, Leong DP, et al. Early and late changes in markers of aortic stiffness with breast cancer therapy. Intern Med J. 2015;45:140\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDrafts BC, Twomley KM, D\u0026rsquo;Agostino R Jr, Lawrence J, Avis N, Ellis LR, et al. Low to moderate dose anthracycline-based chemotherapy is associated with early noninvasive imaging evidence of subclinical cardiovascular disease. JACC Cardiovasc Imaging. 2013;6:877\u0026ndash;85.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMizia-Stec K, Gościńska A, Mizia M, Haberka M, Chmiel A, Poborski W, Gąsior Z. Anthracycline chemotherapy impairs the structure and diastolic function of the left ventricle and induces negative arterial remodelling. Kardiol Pol. 2013;71:681\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Anthracycline, atherosclerosis, breast cancer, dexrazoxane, echocardiography","lastPublishedDoi":"10.21203/rs.3.rs-6990789/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6990789/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eAnthracyclines are used as the main agents for the treatment of breast cancer. Dexrazoxane is one of the main agents used to prevent the cardiotoxic effect of anthracyclines. In this study, the effect of anthracyclines on arteriosclerosis were investigated.\u003c/p\u003e\u003ch2\u003eMaterials and Methods\u003c/h2\u003e\u003cp\u003eSixty patients were included the study who were diagnosed with breast cancer and aged between 23\u0026ndash;58. The patients were divided into two groups by evaluating their age, cancer type, cancer grade and the treatments they received. The study group consisted of 30 patients with breast cancer who received dexrazoxane and the control group consisted of the patients who were similar to the study group and did not receive. Basal oscillometric arterial and echocardiographic cardiac parameters, aortic stiffness and pulse wave velocity (PWV) values of all patients were measured before chemotherapy and 1 month after the chemotherapy protocols were completed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eIn the study group receiving dexrazoxane, only left ventricular end-diastolic pressure increased in oscillometric and echocardiographic measurements before and after treatment (p\u0026thinsp;=\u0026thinsp;0.008), while other parameters were preserved. In the control group, a decrease in ejection fraction (p\u0026thinsp;=\u0026thinsp;0.001), an increase in left ventricular end-diastolic pressure (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), an increase in left ventricular endsystolic pressure (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and an increase in the left atrium anteroposterior diameter (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) were detected. While the PWV value, measured oscillometrically and evaluated as a vascular stiffness parameter, increased significantly in the control group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eIn patients with breast cancer who have received anthracyclines, dexrazoxane protects patients from the negative effects of anthracyclines on arteriosclerosis.\u003c/p\u003e","manuscriptTitle":"Effects of Anthracyclines on Atherosclerosis in Patients with Breast Cancer and Protective Effect of Dexrazoxane","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-21 10:13:59","doi":"10.21203/rs.3.rs-6990789/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e7454e51-daae-459a-a1df-f4ef6f6bf143","owner":[],"postedDate":"July 21st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-10-28T18:02:59+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-21 10:13:59","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6990789","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6990789","identity":"rs-6990789","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}