How to comprehensively evaluate & manage cardiovascular risk in breast cancer survivors?

How to comprehensively evaluate & manage cardiovascular risk in breast cancer survivors? | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 3 December 2025 V1 Latest version Share on How to comprehensively evaluate & manage cardiovascular risk in breast cancer survivors? Author : Chunsong Hu [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.176477051.10389885/v1 234 views 88 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Since there are increasing breast cancer survivors (BCS), how to effectively evaluate & manage their modifiable cardiovascular risk with a comprehensive strategy, including assessing methods and tools, is crucial to reducing the burden of adverse cardiovascular outcomes and improving quality of life in BCS. In this review, data were identified through searches of PubMed for ongoing trials and articles (published in English), including reviews, original research and clinical trial data, mainly from Jan 1, 2015, to Aug 30, 2025. Search terms included “breast cancer”, “breast cancer survivors”, “cardiotoxicity”, “cardiovascular risk factors”, “echocardiography”, “exercise testing”, “long-term or short-term”, “screening tools”, and “treatment”. Emphasis was placed on articles published in cardiovascular journals, focusing on BCS and cardiovascular risk. This article introduces the current status of BCS, discusses E(e)SEEDi-related cardiovascular risk, comments a study on cardiovascular risk factors in BCS, as well as how to effectively evaluate & manage BCS cardiovascular risk with a comprehensive strategy, including assessing methods and tools (such as artificial intelligence application, biomarkers, cardiac imaging, electronic health record-enabled tools, function assessment, genetic testing, HFA-ICOS risk assessment tools, polygenic risk scores, prediction score models, risk prediction equations, self-reported questionnaire, and smartphone-based program), main treatments (systemic anticancer therapies, local anticancer therapies, and other adjunct therapies). Herein, as a vital topic, effectively evaluate & manage cardiovascular risk with a comprehensive strategy, including assessing methods and tools, is beneficial to improvement of BCS cardivoascular health and quality of life as well as life expectancy. This article highlights BCS cardiovascular risk and future perspectives. REVIEW ARTICLE How to comprehensively evaluate & manage cardiovascular risk in breast cancer survivors? Running title: Cardiovascular Risk in BCS Author : Chunsong Hu, M.D., Ph.D. Affiliation : From the Department of Cardiovascular Medicine, Nanchang University, Hospital of Nanchang University, Jiangxi Academy of Medical Science, No. 461 Bayi Ave, Nanchang 330006, Jiangxi, China. Tel: (+86) 189 70816800; Email: [email protected] or [email protected] ; https://orcid.org/0000-0002-0590-3909 Submissions to BJP : No. 26 Word count: 2,934 (Main text) + 245 (Abstract) References: 64 Tables: 2 Figures: 3 Total pages: 25 The author reports no conflicts of interest. Submission Declaration Statement: The manuscript is original, with no portion under simultaneous consideration for publication elsewhere or previously published, and the authors are responsible for the contents and have read and approved the manuscript for submission. Corresponding author: Chunsong Hu, M.D., Ph.D., Associate Professor of Medicine, Department of Cardiovascular Medicine, Jiangxi Academy of Medical Science, Hospital of Nanchang University, Nanchang University, No. 461 Bayi Ave, Nanchang 330006, Jiangxi, China. Tel: (+86) 189 70816800; Email: [email protected] or [email protected] Abstract Since there are increasing breast cancer survivors (BCS), how to effectively evaluate & manage their modifiable cardiovascular risk with a comprehensive strategy, including assessing methods and tools, is crucial to reducing the burden of adverse cardiovascular outcomes and improving quality of life in BCS. In this review, data were identified through searches of PubMed for ongoing trials and articles (published in English), including reviews, original research and clinical trial data, mainly from Jan 1, 2015, to Aug 30, 2025. Search terms included “breast cancer”, “breast cancer survivors”, “cardiotoxicity”, “cardiovascular risk factors”, “echocardiography”, “exercise testing”, “long-term or short-term”, “screening tools”, and “treatment”. Emphasis was placed on articles published in cardiovascular journals, focusing on BCS and cardiovascular risk. This article introduces the current status of BCS, discusses E(e)SEEDi-related cardiovascular risk, comments a study on cardiovascular risk factors in BCS, as well as how to effectively evaluate & manage BCS cardiovascular risk with a comprehensive strategy, including assessing methods and tools (such as artificial intelligence application, biomarkers, cardiac imaging, electronic health record-enabled tools, function assessment, genetic testing, HFA-ICOS risk assessment tools, polygenic risk scores, prediction score models, risk prediction equations, self-reported questionnaire, and smartphone-based program ), main treatments (systemic anticancer therapies, local anticancer therapies, and other adjunct therapies). Herein, as a vital topic, effectively evaluate & manage cardiovascular risk with a comprehensive strategy, including assessing methods and tools, is beneficial to improvement of BCS cardivoascular health and quality of life as well as life expectancy. This article highlights BCS cardiovascular risk and future perspectives. Keywords: Anticancer treatment; Breast cancer survivors; Cardiotoxicity; Cardiovascular risk; Evaluation & Management Graphical Abstract Abbreviations BCS breast cancer survivors CAC coronary artery calcification CAD coronary artery disease CDC CVD, diabetes, and cancer CPET cardio-pulmonary exercise testing CR cardiac rehabilitation CVD cardiovascular disease HF heart failure HFpEF HF with preserved ejection fraction HFrEF HF with reduced ejection fraction IHD ischemic heart disease LVEF left ventricular ejection fraction LVSD left ventricular systolic dysfunction RT radiation therapy 1 | INTRODUCTION Currently, cancer has become the leading killer of human health. Breast cancer is the most common cancer among women worldwide. In 8 females, one will be diagnosed with breast cancer in their lifetime. In fact, female breast cancer represents the highest incidence of cancer globally. Due to medical advances in screening, diagnostic techniques and treatments, and prevention and care, breast cancer survival rates have significantly improved and overall survival times are longer with over 7.8 million women surviving 5 years post-diagnosis globally. However, breast cancer survivors (BCS) are at greater cardiovascular risk for morbidity and mortality due to anticancer therapies such as radiotherapy and shared risk factors in both cancer and cardiovascular disease (CVD), particularly greater numbers of elderly BCS are at risk for CVD. Herein, CVD is still the leading cause of death among BCS. This article introduces the current status of BCS, discusses E(e)SEEDi-related cardiovascular risk among BCS, and comments a recent study on cardiovascular risk factors in BCS [1], as well as how to effectively evaluate & manage BCS cardiovascular risk with a comprehensive strategy. It aims to highlights BCS cardiovascular risk and future perspectives. 2 | CARDIOVASCULAR RISK AMONG BCS 2.1. BCS-related risk factors Several factors link to the potential risk of developing primary and secondary breast cancer, including treatment modalities (the late effects of radiotherapy and other treatment exposures) and unhealthy lifestyle, such as active and passive smoking and alcohol consumption. High genetic etiology [2], for example, a family history of cancer, plays a vital role in new-onset cancer. Usually, individuals with cancer including BCS have a greater number of unfavorable social determinants of health [3], higher risk of fatigue, sexual dysfunction, accelerated aging [4], sleep problems, anxiety and depression, pain and receipt of opioid analgesics. And mental health [5] being a major source of disability. In fact, there are also gender-specific risks for osteoporosis and fractures in BCS, and a series of shared risk factors, such as obesity, smoking, and an unhealthy diet among BCS and CVD. 2.2. E(e)SEEDi-related cardiovascular risk in BCS Cardiovascular risk and adverse outcomes among cancer survivors are higher than in the general population. The short-term risk of cardiovascular death is due to traumatic psychological stress after a breast cancer diagnosis and the acute cardiotoxicity of systemic anticancer treatments [6]. And there is higher risk of cardiovascular mortality among cancer survivors [7,8]. In fact, all female BCS are associated with the increased risk for atrial fibrillation (AF), heart failure (HF), and cardiovascular death, but depending on population characteristics with variations by cancer type, ethnicity and socioeconomical conditions. 9 Cardiac dysfunction is the leading cause of mortality among 10-year BCS after cardiotoxic therapy (anthracyclines, radiation, and trastuzumab/pertuzumab therapy). Among BCS age > 50 years, deaths due to CVD account for 35% of non-cancer related deaths due to a higher prevalence of shared risk factors, and the cardiotoxic effects of cancer treatment [10]. The following is a systemic summary (Table 1 & Graphical Abstract). Firstly, BCS face greater cardiometabolic risks [11]. For example, BCS had elevated risks of diabetes and hypertension. Some would have a first acute myocardial infarction at an older age. BCS might have an excess risk of having subclinical left ventricular dysfunction over time, and an increased cardiovascular risk due to vascular calcification, for example, thoracic aortic calcification and chronic ischemic heart disease (IHD) [12]. In addition, stroke incidence is significantly increased after diagnosis of BCS. Secondly, cardiotoxicity is the most common phenomenon among BCS, which is associated with short or long-term side effects (Table 2) of cancer multimodal treatment [13,14] due to changing patients’ internal environment and the pro-inflammatory microenvironment, including systemic chemotherapy by agents, such as anthracyclines and trastuzumab, endocrine therapy or hormone therapy, immune checkpoint inhibitors, and local radiation therapy (RT) [15]. All BCS are at risk of late treatment-related toxicities. These BCS are more likely to develop CVD than non-cancer subjects. However, there are the disparities of cardiotoxicity among race, ethnicity, and/or socioeconomic status [16]. Some patients (e.g., Asian Indian and Pakistani) with BCS had higher risks of HF, IHD and death. Age, diastolic function, and strain value in BCS who underwent chemotherapy has a long-term effect on CVD. For example, long-term BCS with anthracyclines therapy is effective, but at risk of late effects, such as reduced cardiorespiratory fitness and increased risk of CVD. There are increased long-term risks of cardiomyopathy and/or heart failure (HF) and IHD, asymptomatic left ventricular systolic dysfunction (LVSD) [17], abnormal cardiac biomarkers and cardiac risk factors, among BCS treated with anthracyclines and/or trastuzumab, and atrial febrillation (AF) among BCS after surgery. Young women treated with RT for left-sided breast cancer had over twice the risk of coronary artery disease (CAD) due to greater heart radiation exposure and radiation-associated CVD [17]. Thirdly, comorbidities are also pivotal cardiovascular risk among BCS. When there are comorbidities (such as preexisting CVD including hypertension, hypercholesterolemia, diabetes, peripheral artery disease [18], and HF, etc.), particularly other cancers (such as Hodgkin lymphoma), BCS have a higher risk of CVD or breast cancer events (recurrences/metastases). Moreover, the number and types of comorbidities link to low or high risk of CVD. In fact, all BCS experience an increased burden of long-term comorbidities, including HF and its subtypes, such as HF with preserved ejection fraction (HFpEF), and HF with reduced ejection fraction (HFrEF) [19], older, racially diverse BCS, the incidence of HFpEF, as defined by HF hospitalizations, was higher than HFrEF, and associated with an increased mortality risk. Herein, CVD is one of the most common comorbidities in BCS, and more comorbidities, more at risk for CVD. Fourthly, complications of BCS (short or long-term) and its therapies may increase the risk of CVD. Improvements in early detection and treatment of cancer have led to an increasing number of survivors, but these BCS are at risk of long-term cardiac complications from cancer treatment, for example, AF [20]. Adult BCS have significantly higher risk of CVD, especially HF, independent of traditional cardiovascular risk factors [21]. In addition, CV risk also links to specific cancer sites, stage at diagnosis, and histologic types. For example, there is a significantly higher accelerated coronary artery calcification (CAC) burden [22] (also a sign of preclinical atherosclerosis), atherosclerotic plaque and coronary artery stenosis in BCS after adjuvant RT, in particularly left-side than right-side. Herein, there is an unmet need to define strategies for cardiovascular risk and CVD prevention in BCS as the high-risk population. Lastly, unhealthy lifestyle -related multiple modifiable risk factors overlap for breast cancer and CVD, such as older age, early menarche, high body mass index, body composition [23], depression [24], neighborhood stressors and allostatic load in BCS, physical inactivity or limited exercise (e.g., subjective slow gait speed) [25], smoking, Western diet and duration of aromatase inhibitor (AI) use highly link to long-term cardiovascular risk in BCS. Moreover, unhealthy lifestyles link to the risk for recurrence, second primary cancers, and incidence of new comorbid conditions, including CVD. 3 | COMMENTS ON THE STUDY IN INTERNATIONAL JOURNAL OF CARDIOLOGY In a recent single-center, retrospective study, Dr. Wernhart, et al [1] . found that new-onset arterial hypertension is the most common acquired risk among a group of BCS at low levels of cardiovascular risk at baseline after assessed by cardio-pulmonary exercise testing (CPET), echocardiography and the H 2 FPEF score, and breast cancer treatment regimens had no relevant impact on treatment-related cardiotoxicity. This is really a good news to all BCS globally, since these results can help to targeted prevention and management of major treatment-related side-effects. On the one hand, this study confirmed the crucial concepts of CDC strips and Re-CDC strips [26,27]. On the other hand, there are available of low-harm treatment agents and therapies (e.g., anthracycline, HER2-targeted therapy or endocrine therapy). Fig. 1 Methods and Tools of Major Cardiovascular Risk Assessment. But there are still pending questions due to a small number of patients and the follow-up was less than 2 years. In addition, strain and biomarkers were not available in this study. These may also restrict the results for expanding application in a large-scale population. As we know, there are racial disparities in cardio-oncology, e.g., Black BCS’ increased burden of cardiovascular risk factors. At the same time, the potential benefits of echocardiographic assessment in BCS are sure, but it’s just a part of the availability of monitoring with imaging resources among more tools of evaluation (Table 2 & Fig. 1). In future research, more healthy lifestyle components should be adopted into the intervention in larger samples with a longer follow-up. 4 | HOW TO COMPREHENSIVELY EVALUATE & MANAGE CARDIOVASCULAR RISK AMONG BCS? Due to the significant advances in oncological diagnostics and therapy, the number of BCS has been growing substantially. But CVD substantially contributes to mortality and morbidity in these BCS. In fact, about half of the patients with some cancers (such as breast, prostate, endometrial and thyroid cancer) dies from CVD. Herein, it is increasingly important for clinicians to appropriately and prioritized manage the risk of CVD among BCS, and how to comprehensively evaluate & manage cardiovascular risk in BCS is a crucial topic in the clinical. Moreover, people need innovative cardio-oncology programs for the long-term management of BCS. Here, the reviewer strongly recommends the iRT-ABCDEFG strategy [28,29] for comprehensive evaluation & management of cardiovascular risk in BCS. After setting a feasible and realistic goals (e.g., a personalized care of BCS is achievable only through multidisciplinary-guided care programs for higher quality of life, longer life expectancy, and less adverse outcomes) for all registered BCS, persisting sustained short or long-term follow-up care is essential for safe cancer therapy, so as to monitor for long-term cardiac effects and optimize cardiovascular health [30]. Then, a comprehensive cardiovascular evaluation before, during, and after cancer treatment by systemic examination or long-term annual screening (e.g., cancer-related fatigue), including a detailed medical history, physical examination, biomarkers assay, baseline cardiac imaging, and other tools like nomogram [31], risk prediction equations of CVD – a reasonable clinical tool in New Zealand [32], and the automated heart-health assessment (AH-HA) clinical decision support tool [33], so as to get better early diseases and risk control . As we know, monitoring and managing cardiovascular risk and risk stratification at the time of breast cancer diagnosis [34] are essential for safer cancer therapy. At the same time, changing unhealthy E(e)SEEDi lifestyle-related risk factors (such as physical inactivity and smoking), since aerobic exercise and resistance training may reduce the 10-year risk of developing CVD by 15% in BCS. In addition, actively adjust and control abnormal biomarkers (Table 1 & Fig. 2), like inflammatory biomarkers (TNF-α, IL-6, GDF15, CRP) [35], oxidative stress markers [36], TyGi [37], NT-proBNP [38], and PBSUPAR levels [39]. Lastly, there is a need for agents and/or non-pharmaceutical (Table 2 & Fig. 2) antagonistic therapy . These comprehensive strategies may reduce the risk of the development of cardiac morbidity and mortality and would increase the number of BCS. However, we should also know that anticancer drugs of adjuvant chemotherapy in females BCS, particularly in older patients and those receiving anthracyclines with comorbidity, may increase the risk for cancer therapy-related cardiovascular toxicity, which in turn contributes to CVD. Fig. 2 Main Treatments for Breast Cancer. As we know, there are baseline cardiac risk assessment and surveillance strategies for the type of cardiovascular risk evaluation (biomarkers assay and cardiac imaging), there are also useful CAD risk prediction tools include genetic testing, polygenic risk scores and clonal hematopoiesis markers, and risk stratification tools can aid in determining the individuals’ risk profile. Current Life’s Essential 8 could be applicable for cardiovascular health metrics and CVD risk stratification among BCS [40], but it’s incomplete since there are no indicators of sleep and emotion. For example, low handgrip strength, as a simple and modifiable indicator, is associated with a higher risk of depression in BCS. In fact, improvements in early detection and treatment of cancer have led to an increasing number of BCS, but these BCS are still at risk of long-term cardiac complications from cancer treatment. As recommended in the new guidelines of the European Society of Cardiology, risk stratification before treatment is crucial to identify high-risk patients who would benefit most from the use of cardioprotective strategies, for example, therapeutic strategies such as the potential role of dexrazoxane, alterations in anthracycline dosing or formulation, radiation delivery strategies, neurohormonal antagonists, angiotensin-converting enzyme inhibitors [41], angiotensin, beta receptor blockers, statin [42], sacubitril/valsartan, the possibility of using gliflozins, and combination therapy. Of course, increasing physical activity [43] may contribute to cardiovascular health benefits due to potentially decreasing the risk of IHD and stroke in long-term BCS. In summary, all BCS should receive a comprehensive evaluation based on patients’ cardiovascular risk level and the type, amount and duration of cancer therapies received during the patient’s lifetime. At the same time, to promptly recognize and manage cardiovascular risk factors before, during, and after cancer treatment is crucial to decreasing the risk of cancer therapy-related cardiac dysfunction. If left ventricular ejection fraction (LVEF) deteriorates (e,g., worsening heart failure ) [44,45] during cancer treatment (from >10% to in GLS), early initiation of cardioprotective therapies is recommended, and LVEF should be reassessed before discontinuation. Long-term cardiac screening (cholesterol screening and statin therapy), and warranting follow-up and/or intervention, cancer care delivery innovations, a cardiac rehabilitation intervention, for example, circuit resistance training is effective for improving muscle and cardiorespiratory fitness. Healthy E(e)SEEDi lifestyle [46], such as good social and built environment [47], psychosocial functioning, regular physical activity (e.g., walking, gamification [48]) and a nutritious diet (e.g., the Mediterranean diet), are protective against CVD, diabetes, and cancer recurrence in BCS. In fact, leisure-time exercise (such as aerobic and muscle-strengthening) can lower the risk of various adverse cardiovascular outcomes. However, most BCS do not meet exercise guidelines. In BCS, improved dietary fat and carbohydrate quality (i.e., more unsaturated fatty acids and fiber) [49] is associated with favorable cardiac function, while higher sucrose is associated with worse cardiac function. In fact, high genetic risk individuals among BCS could benefit more from adherence to a healthy lifestyle in reducing CVD risk [50]. All in all, these comprehensive strategies, the favorable health education, preventative medical care, greater motivation for a healthier lifestyle [51], participation in BCS programs (e.g., a smartphone delivered intervention [52]), and cardiac rehabilitation (CR) for secondary prevention [53], are very helpful to BCS care. In addition, interdisciplinary cardio-oncology cooperation is pivotal for optimal management of BCS. 5 | CONCLUSIONS AND FUTURE PERSPECTIVES All BCS face unique challenges and require ongoing care. Those with more comorbidities will have poorer cancer outcomes and higher mortality. Herein, early diagnosis and increased awareness among patients, healthcare professionals, and policy makers are likely to be important to mitigate the impacts of these raised risks among BCS. Better understanding and managing the long-term health of BCS need removing barriers to receive preventive care, adding cardio-oncology rehabilitation, practicing cultural humility, and adhering to evidence-based guidelines for behavioral risk management for BCS, as well as multidisciplinary decision-making regarding the BCS treatment. There is an increasing need for the clinical care of BCS patients with rigorous, evidence-based medicine. The prognosis of BCS has dramatically improved, but effective strategies for cancer treatment-related cardiovascular risk and outcomes remain to be elucidated in the emerging field of cardio-oncology. Particularly, regular cardiovascular assessments, lifestyle modifications, and collaboration between healthcare professionals [54] are crucial in managing BCS cardiotoxicity effectively. Communication between oncologists and preventive care providers is essential so as to avoid redundancy. A customized individualization strategy [55] considering each patient’s cardiovascular risk factors and follow-up plans are needed during all cancer multimodality therapies [56], particularly AI treatment. And we should develop strategies to minimize adverse cardiovascular events and improve patient outcomes. Collaboration between oncologists and cardiologists [57] as well as cancer knowledge and tools [58] are critical for managing an ageing cancer population and their potential health risks, and improvement of secondary prevention, emotional health, recovery, and long-term outcomes [59]. The significance of shared-care models and telemedicine options are great prospects in cancer management. Effectively preventing, consistently monitoring, promptly diagnosing, and timely treating are crucial to decreasing breast cancer treatment-related cardiovascular risk and outcomes and extending the life expectancy of BCS. All in all, cardio-oncology has been an emerging discipline to manage cardiovascular health in cancer patients throughout and following cancer treatment. And developing novel and translational therapies for doxorubicin-induced cardiac dysfunction and cardiac rehabilitation [60,61] need a good cooperation among multidisciplinary teams of experts based on molecular mechanisms of anticancer agents induced cardiotoxicity, such as to oxidative stress, cardiomyocyte apoptosis and pyroptosis, and autophagy [62-64]. Since there are increasing BCS, control of comprehensive modifiable risk factors is a crucial strategy for reducing the burden of adverse cardiovascular outcomes and improving quality of life in these survivors. Chunsong Hu contributed to conceptualization, data analysis, methodology, resources, visualization, writing-original draft, and writing-review & editing. The author read and approved the final version of this manuscript. The author did not receive any funding or material support and gratefully acknowledges the reviewers and editors for their critical reviews. The author declared no competing interests for this work. DISCLAIMER The views expressed in this article are the personal views of the author and may not be understood or quoted as being made on behalf of or reflecting the position of the regulatory agency/agencies or organizations with which the author is employed/affiliated. REFERENCE 1. Wernhart S, Fiorentini C, Glowka S, et al. Evaluating cardiovascular risk factors in breast cancer survivors: The role of echocardiography and cardiopulmonary exercise testing in the Munich Cardio-Oncology-Exercise retrospective Registry. Int J Cardiol 2025;436:133421, doi: 10.1016/j.ijcard.2025.133421. 2. Gibson TM, Karyadi DM, Hartley SW, et al. Polygenic risk scores, radiation treatment exposures and subsequent cancer risk in childhood cancer survivors. Nat Med 2024;30:690-8. 3. Huang H, Wei T, Huang Y, et al. Association between social determinants of health and survival among the US cancer survivors population. BMC Med 2024;22:343. 4. Yeh JM, Ward ZJ, Stratton KL, et al. Accelerated Aging in Survivors of Childhood Cancer-Early Onset and Excess Risk of Chronic Conditions. JAMA Oncol 2025;11:535-43. 5. Carreira H, Williams R, Funston G, Stanway S, Bhaskaran K. Associations between breast cancer survivorship and adverse mental health outcomes: A matched population-based cohort study in the United Kingdom. PLoS Med 2021;18:e1003504. 6. Johansen SH, Wisløff T, Edvardsen E, et al. Effects of Systemic Anticancer Treatment on Cardiorespiratory Fitness: A Systematic Review and Meta-Analysis. JACC CardioOncol 2025;7:96-106. 7. Galimzhanov A, Istanbuly S, Tun HN, et al. Cardiovascular outcomes in breast cancer survivors: a systematic review and meta-analysis. Eur J Prev Cardiol 2023;30:2018-31. 8. Bhalraam U, Veerni RB, Paddock S, et al. Impact of sodium-glucose cotransporter-2 inhibitors on heart failure outcomes in cancer patients and survivors : a systematic review and meta - analysis . Eur J Prev Cardiol 2025;zwaf026. 9. Szabo L, Cooper J, Condurache DG, et al. Cardiovascular disease burden and risk factor management in cancer survivors: insights into a multiethnic, socioeconomically deprived urban population. Heart 2025;heartjnl-2024-325309. 10. Coughlin SS, Ayyala D, Majeed B, Cortes L, Kapuku G. Cardiovascular Disease among Breast Cancer Survivors. Cardiovasc Disord Med 2020;2:10.31487/j.cdm.2020.01.01. 11. Fillon M. Breast cancer survivors face greater cardiometabolic risks. CA Cancer J Clin 2022;72:303-4. 12. Ali E, Ur Rahman HA, Kamal UH, et al. Trends and regional variations in chronic ischemic heart disease and lung cancer-related mortality among American adults: Insights from retrospective CDC wonder analysis. Int J Cardiol Cardiovasc Risk Prev 2025;24:200377. 13. Kidane RD, Ruddy KJ, Lin G, Sandhu NP. Cardiovascular Health Considerations for Primary Care Physicians Treating Breast Cancer Survivors. Mayo Clin Proc 2025;100:124-40. 14. Velusamy R, Nolan M, Murphy A, Thavendiranathan P, Marwick TH. Screening for Coronary Artery Disease in Cancer Survivors: JACC: CardioOncology State-of-the-Art Review. JACC CardioOncol 2023;5:22-38. 15. Meattini I, Poortmans PM, Aznar MC, et al. Association of Breast Cancer Irradiation With Cardiac Toxic Effects: A Narrative Review. JAMA Oncol 2021;7:924-32. 16. Wilson OWA, Wojcik KM, Cohen CM, et al. Exercise and cardiovascular health among breast cancer survivors: a scoping review of current observational evidence. Cardiooncology 2025;11:24. 17. Glen C, Morrow A, Roditi G, et al. Cardiovascular sequelae of trastuzumab and anthracycline in long-term survivors of breast cancer. Heart. 2024;110(9):650-656. 18. Nohara S, Mok Y, Van’t Hof JR, et al. Subsequent risk of cancer among adults with peripheral artery disease in the community: The atherosclerosis risk in communities (ARIC) study. Int J Cardiol 2025;418:132577. 19. Yogeswaran V, Wadden E, Szewczyk W, et al. A narrative review of heart failure with preserved ejection fraction in breast cancer survivors. Heart 2023;109:1202-7. 20. Park YM, Jung W, Yeo Y, et al. Mid- and long-term risk of atrial fibrillation among breast cancer surgery survivors. BMC Med 2024;22:88. 21. Florido R, Daya NR, Ndumele CE, et al. Cardiovascular Disease Risk Among Cancer Survivors: The Atherosclerosis Risk In Communities (ARIC) Study. J Am Coll Cardiol 2022;80:22-32. 22. Krug P, Geets X, Berlière M, et al. FESC FACC FAHA. Coronary artery calcification severity in long term breast cancer survivors treated with isolated contemporary radiotherapy: Relation to dose and CV risk factors. Eur J Radiol 2025;183:111909. 23. Kim JS, Song J, Choi S, et al. Association between body composition and subsequent cardiovascular diseases among 5-year breast cancer survivors. Nutr Metab Cardiovasc Dis 2024;34:1787-97. 24. Khubchandani J, Banerjee S, Batra K, Beydoun MA. Depression Is Associated with a Higher Risk of Mortality among Breast Cancer Survivors: Results from the National Health and Nutrition Examination Survey-National Death Index Linked Study. Brain Sci 2024;14:732. 25. Ohno R, Kaneko H, Ueno K, et al. Subjective Gait Speed and Risk of Developing Cardiovascular Events in 56,589 Cancer Survivors. Int Heart J 2023;64:672-7. 26. Hu CS, Wu QH, Hu DY. Cardiovascular, diabetes, and cancer strips: evidences, mechanisms, and classifications. J Thorac Dis 2014;6:1319-28. 27. Hu CS, Wu QH, Hu DY, Tkebuchava T. Novel strategies halt cardiovascular, diabetes, and cancer strips. Chronic Dis Transl Med 2017;3:159-64. 28. Hu CS. Intervention of RT-ABCDEF for cancer. Croat Med J 2019;60:55-7. 29. Hu C, Tkebuchava T, Wu Q. A Novel Comprehensive Program Combining Optimal Medical Treatment with Lifestyle Modification for Type 2 Diabetes. Cardiovasc Sci 2024;1:10004. doi.org/10.35534/cvs.2024.10004. 30. Shibata T, Nohara S, Morikawa N, et al. Cardiovascular adverse events and prognosis in patients with haematologic malignancies and breast cancer receiving anticancer agents: Kurume-CREO Registry insights. Eur J Prev Cardiol 2023;30:1941-9. 31. Hu C. Nomogram: A better method for evaluating MVD risk. Int J Cardiol 2024;411:132283. 32. Tawfiq E, Selak V, Elwood JM, et al. Performance of cardiovascular disease risk prediction equations in more than 14 000 survivors of cancer in New Zealand primary care: a validation study. Lancet 2023;401:357-65. 33. Weaver KE, Dressler EV, Klepin HD, et al. AH-HA Study Team. Effectiveness of a Cardiovascular Health Electronic Health Record Application for Cancer Survivors in Community Oncology Practice: Results From WF-1804CD. J Clin Oncol 2025;43:46-56. 34. Murphy AC, Koshy AN, Farouque O, et al. Cardiovascular Disease in Patients With Breast Cancer Treated in the Modern Era. Heart Lung Circ 2024;33:648-56. 35. Cousin L. Cardio-oncology disparities: Interplay of psychosocial stress, inflammation, and cardiometabolic health among Black breast cancer survivors. Am Heart J Plus 2024;38:100366. 36. Vasbinder A, Cheng RK, Heckbert SR, et al. Chronic Oxidative Stress as a Marker of Long-term Radiation-Induced Cardiovascular Outcomes in Breast Cancer. J Cardiovasc Transl Res 2023;16:403-13. 37. Hu C. TyGi: A broad-spectrum clinical marker beyond CVD. Int J Cardiol 2025;420:132750. 38. Jacobse JN, Steggink LC, Sonke GS, et al. Myocardial dysfunction in long-term breast cancer survivors treated at ages 40-50 years. Eur J Heart Fail 2020;22:338-46. 39. Yadalam AK, Liu C, Sun YV, Mandawat A, Quyyumi AA, Hayek SS. Proteomics-Based Soluble Urokinase Plasminogen Activator Receptor Levels and Long-Term Cardiovascular Outcomes in Survivors of Breast Cancer: A UK Biobank Study. J Am Heart Assoc 2025;14:e039728. 40. Ositelu KC, Peesay T, Garcia C, Akhter N. Life’s Essential 8 and Cardiovascular Disease in Breast Cancer Survivors. Curr Cardiol Rep 2025;27:55. 41. Bisceglia I, Mistrulli R, Cartoni D, Matera S, Petrolati S, Canale ML. Cardiac toxicity of chemotherapy for breast cancer: do angiotensin-converting enzyme inhibitors and beta blockers protect? Eur Heart J Suppl 2023;25:B25-7. 42. Huang YJ, Lin JA, Chen WM, Shia BC, Wu SY. Statin Therapy Reduces Radiation-Induced Cardiotoxicity in Patients With Breast Cancer Receiving Adjuvant Radiotherapy. J Am Heart Assoc 2024;13:e036411. 43. Naaktgeboren WR, Groen WG, Jacobse JN, et al. Physical Activity and Cardiac Function in Long-Term Breast Cancer Survivors: A Cross-Sectional Study. JACC CardioOncol 2022;4:183-91. 44. D’Elia E, Zucchetti O, Pedrazzoli F, et al. Assessing palliative care needs in worsening heart failure patients: Insights from OPPORTUNITIES registry. Int J Cardiol 2025;437:133491. 45. Berlin E, Ko K, Ma L, et al. Cardiac Effects of Modern Breast Radiation Therapy in Patients Receiving Systemic Cancer Therapy. JACC CardioOncol 2025; 7 :219-30. 46. Hu C. Prevention of cardiovascular disease for healthy aging and longevity: A new scoring system and related “mechanisms-hallmarks-biomarkers”. Ageing Res Rev 2025;107:102727. 47. Sánchez-Díaz CT, Babel RA, Iyer HS, et al. Neighborhood Archetypes and Cardiovascular Health in Black Breast Cancer Survivors. JACC CardioOncol 2024;6:405-18. 48. Fanaroff AC, Orr JA, Anucha C, et al. A randomized controlled trial of gamification to increase physical activity among black and Hispanic breast and prostate cancer survivors: Rationale and design of the ALLSTAR clinical trial. Am Heart J 2025;280:42-51. 49. Bellissimo MP, Carbone S, He J, et al. Higher diet quality relates to better cardiac function in cancer survivors: The multi-ethnic study of atherosclerosis. Prog Cardiovasc Dis 2023;81:10-6. 50. Peng H, Wang S, Wang M, et al. Lifestyle Factors, Genetic Risk, and Cardiovascular Disease Risk among Breast Cancer Survivors: A Prospective Cohort Study in UK Biobank. Nutrients 2023;15:864. 51. Yandrapalli S, Malik AH, Pemmasani G, et al. Risk Factors and Outcomes During a First Acute Myocardial Infarction in Breast Cancer Survivors Compared with Females Without Breast Cancer. Am J Med 2020;133:444-51. 52. Murphy AC, Farouque O, Yeo B, et al. SMARTphone Based Cardiovascular Risk Reduction in BREAST Cancer Patients (SMART-BREAST): A Randomised Controlled Trial Protocol. Heart Lung Circ 2021;30:1314-9. 53. Hollings M, Gordon N, Redfern J, et al. Characteristics and Outcomes of Cardiac Rehabilitation Patients With and Without Cancer: Insights From Western Sydney. Heart Lung Circ 2024;33:730-7. 54. Kidane RD, Ruddy KJ, Lin G, Sandhu NP. Cardiovascular Health Considerations for Primary Care Physicians Treating Breast Cancer Survivors. Mayo Clin Proc 2025;100:124-40. 55. Bisceglia I, Canale ML, Silvestris N, et al. Cancer survivorship at heart: a multidisciplinary cardio-oncology roadmap for healthcare professionals. Front Cardiovasc Med 2023;10:1223660. 56. Parashar S, Akhter N, Paplomata E, et al. Cancer Treatment-Related Cardiovascular Toxicity in Gynecologic Malignancies: JACC: CardioOncology State-of-the-Art Review. JACC CardioOncol 2023;5:159-73. 57. Wang Z, Fan Z, Yang L, et al. Higher risk of cardiovascular mortality than cancer mortality among long-term cancer survivors. Front Cardiovasc Med 2023;10:1014400. 58. Weaver KE, Dressler EV, Smith S, et al. Cardiovascular health assessment in routine cancer follow-up in community settings: survivor risk awareness and perspectives. BMC Cancer 2024;24:158. 59. Dieffenbach BV, Murphy AJ, Liu Q, et al. Cumulative burden of late, major surgical intervention in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study (CCSS) cohort. Lancet Oncol 2023;24:691-700. 60. Lu D, Chatterjee S, Xiao K, et al. A circular RNA derived from the insulin receptor locus protects against doxorubicin-induced cardiotoxicity. Eur Heart J 2022;43:4496-511. 61. Adams SC, Rivera-Theurel F, Scott JM, et al. Cardio-oncology rehabilitation and exercise: evidence, priorities, and research standards from the ICOS-CORE working group. Eur Heart J 2025;ehaf100. 62. Ma Y, Wang Y, Chen R, et al. Exosomal transfer of pro-pyroptotic miR-216a-5p exacerbates anthracycline cardiotoxicity through breast cancer-heart pathological crosstalk. Signal Transduct Target Ther 2025;10:157. 63. Zhu M, Yang Y, Fang H, Chen R. Inetetamab triggers cardiotoxicity through its interaction with apoptosis, oxidative stress and autophagy pathways. Sci Rep 2025;15:20987. 64. Zhu M, Yang Y, Fang H, Chen R. Exploring the mechanism of action of trastuzumab-induced cardiomyocyte atrophy based on the FN1/PI3K/AKT-mediated mTOR-independent signaling pathway. Genomics 2025;117:111087. Table 1. E(e)SEEDi-related major cardiovascular risk and evaluation in BCS. E(e)SEEDi Major Cardiovascular Risk Methods & Tools of Risk Assessment Environment (external) Social determinants of health (SDoH) A greater number of unfavorable SDoH was associated with increased risks of mortality from all causes and cancer Air pollution E-noise Environmental radiation Residential and working environments Socio-ecological frameworks link to poorer outcomes and higher mortality among black women Neighborhood archetypes, integrating social and built environment factors, may represent crucial targets for promoting cardiovascular health among BCS Environment (internal) Cardiometabolic risks diabetes and hypertension subclinical myocardial damage (such as heart attack, angina pectoris, myocardial infarction, congestive heart failure, or ischemic stroke), subclinical LV dysfunction Cardiotoxicity Cancer multimodal treatment-related short and long-term side effects due to changing patients’ internal environment, including cardiac injury, CT and/or RT related major adverse cardiovascular events (MACE), such as treatment-resistant hypertension, acute myocarditis, acute coronary ischemia with plaque rupture or vasospasm, thromboembolism, arrhythmia, pulmonary hypertension, diastolic dysfunction, heart failure, and others (aging-related diseases) Comorbidities (the number and types) Preexisting CVD, such as hypertension, hypercholesterolemia, diabetes, myocardial infarction, congestive heart failure, cerebrovascular disease, peripheral vascular disease, etc. Non-cardiac diseases, such as Hodgkin lymphoma Complications of cancer and its therapies Abdominal adiposity (Excessive abdominal fat) & overweight Altered lipid profile Subclinical LV dysfunction Stroke incidence significantly increased Conventional cardiovascular risks A family history of cancer or CVD Cancer or CVD individual history (such as coronary artery disease, hypertension and stroke history) Depression and anxiety Fasting blood sugar High BMI, obesity in African American Hypertension Increased HF risk in rural residence (particularly HFpEF) Metabolic syndrome (overweight, general obesity, abdominal obesity, diabetes) linked to increased breast cancer incidence and worse survival Older women Systolic blood pressure TyGi Waist circumference triglycerides Women with lower education attainment Vascular calcification (e.g., thoracic aortic calcification) Artificial intelligence application (e.g., machine learning models) AI can enhance the accuracy and efficiency of cardiotoxicity assessments in BCS Biomarkers in serum Oxidative stress (such as myeloperoxidase, GDF-15, 8-OH-dG, placental growth factor), cardiac injury (cTnI, cTnT, cystatin-C), inflammation (CRP, IL-6, TNF-α), myocardial fibrosis (TGF-ß), and cardiac disfunction (TyGi, NT-proBNP) Cardiac imaging CT, ECHO, PET, cardiac magnetic resonance (CMR), SPECT as diagnostic assessment E.g., echocardiographic surveillance for LVEF Clinical Guidelines & Expert Consensus and Statement Electronic health record-enabled tools For categorization of cardiovascular risk factors (the integration of such apps), the automated heart-health assessment (AH-HA) clinical decision support tool Function assessment such as cancer-related fatigue, handgrip strength, subjective slow gait speed Genetic testing BRCA1/2 mutations, carriers of any mosaic chromosomal alterations/mCA = an increased risk of CAD death HFA-ICOS risk tools Heart Failure Association & International Cardio-Oncology Society risk assessment tools Polygenic risk scores Nomogram for ageing-related diseases, such as MVD Prediction score models Such as conventional risk factors and treatment-related risk factors (e.g., the CHEMO-RADIAT score) Risk prediction equations of CVD A reasonable clinical tool in New Zealand Self-reported questionnaire BMI, financial or psychological distress, fear of cancer recurrence, physical activity, diet, quality of life, and endocrine therapy adherence Smartphone-based program Sleep Poor sleep quality & short sleep time (insomnia, OSA, stay up later) Emotion Cancer-related long-term, severe fatigue Psychological factors Sexual inactivity Stressful events Exercise Long-term sitting for a long time Physical inactivity Diet Alcoholism or heavy drinking Inadequate diet (e.g., animal food pattern) Low nutritional status (lack of Vitamin D or Omega-3 fat acid) Smoking or passive smoke exposure The Mediterranean or a low-fat diet, and a higher intake of fruits and vegetables are beneficial for various outcomes Notes: Risk assessment by the CHEMO-RADIAT score mainly based on congestive heart failure, hypertension, elderly, myocardial infarction/peripheral artery occlusive disease, obesity, renal failure, abnormal lipid profile, diabetes mellitus, irradiation of the left breast, anthracycline dose, and transient ischemic attack/stroke for overall cardiovascular risk stratification at early-stage. Table 2. Main Treatments of Breast Cancer and Related Cardiotoxicity. Types of Treatment Main Therapies for Breast Cancer Cardiotoxicity: treatment-related side effects Notes Systemic anticancer therapies (single or combination therapy) Chemotherapy (CT): conventional or targeted Anthracyclines Cisplatin Endothelial growth factor inhibitors Fluorouracil Platinum agents Tamoxifen Trastuzumab Endocrine therapy or hormone therapy Aromatase inhibitors (AI) Tyrosine kinase inhibitors Immune checkpoint inhibitors Biological therapy (Antiproliferative cancer drugs) Systemic anticancer therapies can lead to substantial and sustained impairments in cardiorespiratory fitness, and cognitive disorders are common, especially after treated with chemotherapy. Angina is the most common Any type of stroke (ischemic or hemorrhagic) Diabetes Dyslipidemia (the changes in lipid profile) HDL-cholesterol (-) LDL-cholesterol (+) Total cholesterol (+) Hypertension Myocardial infarction Venous thromboembolism The combination therapy may aggravate or alleviate side-effects, for example, trastuzumab± anthracycline The combination of endocrine therapy and chemotherapy is effective in treating breast cancer, but it simultaneously increases the risk of developing a secondary primary cancer (SPC), specifically endometrial cancer. Hydrophilic statins (e.g., rosuvastatin and pravastatin) exhibit the most pronounced cardioprotective effects Local anticancer therapies Whole breast radiation therapy (RT, e.g., thoracic RT) Breast-conserving surgery Radiotherapy-related or radiation-induced endothelial injury, inflammation, and myocardial injury or cardiac damage Preclinical or accelerated atherosclerosis Atherosclerotic plaque The late effects higher accelerated coronary artery calcification (CAC) burden Coronary artery stenosis Treatment-resistant hypertension Acute myocarditis Acute coronary ischemia with plaque rupture or vasospasm Thromboembolism Arrhythmia Pulmonary hypertension Diastolic dysfunction Heart failure, and others Higher risk of contralateral breast cancer and lung cancer Atrial fibrillation after surgery Other adjunct therapies Non-pharmacological intervention Cardiac rehabilitation (CR) (e.g., combined aerobic and resistance training, CART) Healthy E(e)SEEDi lifestyle Pain Management Anesthetic Opioid therapy Revascularization (e.g., PCI) No cardiotoxicity CART may improves body composition, alters cardiometabolic risk, and ameliorates cancer-related indicators in BCS with overweight/obesity, it’s a valuable intervention to lower aggressive pharmacologic use. And there is significant and clinically relevant improvements in peak exercise capacity and waist circumference after CR. No cardiotoxicity The healthy lifestyle can enhance the quality of life and substantially reduce mortality risk in women BCS. Addiction Serious opioid-related harms after long-term opioid therapy This is very helpful but sometimes has a low hazard. Physical rehabilitation program for cardiorespiratory health and quality of life among BCS Notes: Cardiotoxicity is the most common cancer multimodal treatment-related short and long-term side effects due to changing patients’ internal environment and the pro-inflammatory microenvironment, but different anti-cancer treatment strategies can lead to different cardiovascular risks. Herein, crucial comprehensive management strategies include risk stratification, appropriate cardiovascular monitoring, primary prevention, pharmacologic management, and lifestyle interventions (e.g., urban greenspace, tailored exercise programs or continued physical activity, avoidance of smoking, and control of lipids and blood pressure) are beneficial to achieve guideline-recommended targets. In fact, the physiological benefits of the exercise program could improve their quality-of-life domains including physical, mental, and social well-being. Information & Authors Information Version history V1 Version 1 03 December 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Authors Affiliations Chunsong Hu [email protected] Nanchang University View all articles by this author Metrics & Citations Metrics Article Usage 234 views 88 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Chunsong Hu. How to comprehensively evaluate & manage cardiovascular risk in breast cancer survivors?. Authorea . 03 December 2025. DOI: https://doi.org/10.22541/au.176477051.10389885/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . Format Please select one from the list RIS (ProCite, Reference Manager) EndNote BibTex Medlars RefWorks Direct import Tips for downloading citations document.getElementById('citMgrHelpLink').addEventListener('click', function() { popupHelp(this.href); return false; }); $(".js__slcInclude").on("change", function(e){ if ($(this).val() == 'refworks') $('#direct').prop("checked", false); $('#direct').prop("disabled", ($(this).val() == 'refworks')); }); View Options View options PDF View PDF Figures Tables Media Share Share Share article link Copy Link Copied! Copying failed. Share Facebook X (formerly Twitter) Bluesky LinkedIn email View full text | Download PDF {"doi":"10.22541/au.176477051.10389885/v1","type":"Article"} Now Reading: Share Figures Tables Close figure viewer Back to article Figure title goes here Change zoom level Go to figure location within the article Download figure Toggle share panel Toggle share panel Share Toggle information panel Toggle information panel Go to previous graphic Go to next graphic Go to previous table Go to next table All figures All tables View all material View all material xrefBack.goTo xrefBack.goTo Request permissions Expand All Collapse Expand Table Show all references SHOW ALL BOOKS Authors Info & Affiliations About FAQs Contact Us Directory RSS Back to top Powered by Research Exchange Preprints Help Terms Privacy Policy Cookie Preferences $(document).ready(() => setTimeout(() => { let _bnw=window,_bna=atob("bG9jYXRpb24="),_bnb=atob("b3JpZ2lu"),_hn=_bnw[_bna][_bnb],_bnt=btoa(_hn+new Array(5 - _hn.length % 4).join(" ")); $.get("/resource/lodash?t="+_bnt); },4000)); (function(){function c(){var b=a.contentDocument||a.contentWindow.document;if(b){var d=b.createElement('script');d.innerHTML="window.__CF$cv$params={r:'9ffc08b0d9f6f047',t:'MTc3OTQ1NTE0Mg=='};var a=document.createElement('script');a.src='/cdn-cgi/challenge-platform/scripts/jsd/main.js';document.getElementsByTagName('head')[0].appendChild(a);";b.getElementsByTagName('head')[0].appendChild(d)}}if(document.body){var a=document.createElement('iframe');a.height=1;a.width=1;a.style.position='absolute';a.style.top=0;a.style.left=0;a.style.border='none';a.style.visibility='hidden';document.body.appendChild(a);if('loading'!==document.readyState)c();else if(window.addEventListener)document.addEventListener('DOMContentLoaded',c);else{var e=document.onreadystatechange||function(){};document.onreadystatechange=function(b){e(b);'loading'!==document.readyState&&(document.onreadystatechange=e,c())}}}})();