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Current Vascular Pharmacology

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ISSN (Print): 1570-1611
ISSN (Online): 1875-6212

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Review Article

Effects of Exercise on Vascular Toxicity Associated with Breast Cancer Treatment: A Narrative Review

Author(s): Marina L.D. Pera and Guilherme F. Speretta*

Volume 21, Issue 1, 2023

Published on: 18 January, 2023

Page: [42 - 50] Pages: 9

DOI: 10.2174/1570161121666221228141150

Price: $65

Abstract

Breast cancer is the most common cancer among women worldwide, and its incidence is linearly associated with age. The development of cancer treatments has changed the prognosis of this disease. Despite effective treatments, cardiovascular complications in middle-aged and older women have become challenging. Physical exercise is a powerful tool to prevent senescence symptoms and diseases, besides being an essential component for cardiovascular diseases and cancer prevention and treatment. The present narrative review considers the vascular dysfunction associated with breast cancer treatment, specifically chemotherapy and radiotherapy, and the effects of exercise on vascular toxicity. We also explored the mechanisms involved in these responses. The search strategy involved three databases (Pubmed, Scielo, and Web of Science) with the following descriptors: breast cancer, vascular toxicity, physical exercise, chemotherapy, and radiotherapy. The evidence showed that breast cancer patients, especially those under chemotherapy and over 50 years old, have a potential risk of developing vascular dysfunction, which may persist in the long term. Decreases in nitric oxide bioavailability and increases in oxidative stress and pro-inflammatory cytokines might mediate the chemotherapy and radiotherapy- induced vascular dysfunction. Exercise seems to be a promising strategy for managing this risk. However, there is a need for well-constructed studies evaluating vascular toxicity in breast cancer, especially in middle-aged and elderly patients, to establish whether exercise is beneficial.

Keywords: Aging, cardiotoxicity, chemotherapy, physical activity, radiotherapy, breast cancer, vascular dysfunction.

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[1]
World Health Organization. Cancer Today International Agency for research on cancer. Available from 2020.gco.iarc.fr/today/
[2]
National Cancer Institute. Surveillance, Epidemiology, and End Results Program. 2000-2019. Available from: https://seer.cancer.gov/statistics-network/.
[3]
Chang L, Weiner LS, Hartman SJ, et al. Breast cancer treatment and its effects on aging. J Geriatr Oncol 2019; 10(2): 346-55.
[http://dx.doi.org/10.1016/j.jgo.2018.07.010] [PMID: 30078714]
[4]
Wang S, Prizment A, Thyagarajan B, Blaes A. Cancer treatment-induced accelerated aging in cancer survivors: Biology and assessment. Cancers 2021; 13(3): 427.
[http://dx.doi.org/10.3390/cancers13030427] [PMID: 33498754]
[5]
Peel AB, Thomas SM, Dittus K, Jones LW, Lakoski SG. Cardiorespiratory fitness in breast cancer patients: A call for normative values. J Am Heart Assoc 2014; 3(1): e000432.
[http://dx.doi.org/10.1161/JAHA.113.000432] [PMID: 24419734]
[6]
Bouvard B, Soulié P, Hoppé E, et al. Fracture incidence after 3 years of aromatase inhibitor therapy. Ann Oncol 2014; 25(4): 843-7.
[http://dx.doi.org/10.1093/annonc/mdu008] [PMID: 24608193]
[7]
Hurria A, Soto-Perez-de-Celis E, Allred JB, et al. Functional decline and resilience in older women receiving adjuvant chemotherapy for breast cancer. J Am Geriatr Soc 2019; 67(5): 920-7.
[http://dx.doi.org/10.1111/jgs.15493] [PMID: 30146695]
[8]
Wefel JS, Kesler SR, Noll KR, Schagen SB. Clinical characteristics, pathophysiology, and management of noncentral nervous system cancer-related cognitive impairment in adults. CA Cancer J Clin 2015; 65(2): 123-38.
[http://dx.doi.org/10.3322/caac.21258] [PMID: 25483452]
[9]
Albini A, Pennesi G, Donatelli F, Cammarota R, De Flora S, Noonan DM. Cardiotoxicity of anticancer drugs: The need for cardio-oncology and cardio-oncological prevention. J Natl Cancer Inst 2010; 102(1): 14-25.
[http://dx.doi.org/10.1093/jnci/djp440] [PMID: 20007921]
[10]
Fitzmaurice C, Allen C, Barber RM. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: A Systematic analysis for the global burden of disease study global burden of disease cancer collaboration. JAMA Oncol 2017; 3: 524-48.
[http://dx.doi.org/10.1001/jamaoncol.2016.5688] [PMID: 27918777]
[11]
Park NJ, Chang Y, Bender C, et al. Cardiovascular disease and mortality after breast cancer in postmenopausal women: Results from the Women’s Health Initiative. PLoS One 2017; 12(9): e0184174.
[http://dx.doi.org/10.1371/journal.pone.0184174] [PMID: 28934233]
[12]
Kalil Filho R, Hajjar LA, Bacal F, et al. I diretriz brasileira de cardiooncologia da sociedade brasileira de cardiologia. Arq Bras Cardiol 2011; 96(2): 01-52.
[http://dx.doi.org/10.1590/S0066-782X2011000700001] [PMID: 21468528]
[13]
Sandoo A, Kitas G, Carmichael A. Breast cancer therapy and cardiovascular risk: focus on trastuzumab. Vasc Health Risk Manag 2015; 11: 223-8.
[http://dx.doi.org/10.2147/VHRM.S69641] [PMID: 25897242]
[14]
Katzmarzyk PT, Powell K, Jakicic JM, Troiano RP, Piercy K, Tennant B. Sedentary behavior and health: Update from the 2018 physical activity guidelines advisory committee. Med Sci Sports Exerc 2019; 51(6): 1227-41.
[http://dx.doi.org/10.1249/MSS.0000000000001935] [PMID: 31095080]
[15]
Man AWC, Li H, Xia N. Impact of lifestyles (diet and exercise) on vascular health: Oxidative stress and endothelial function. Oxid Med Cell Longev 2020; 2020: 1496462.
[http://dx.doi.org/10.1155/2020/1496462] [PMID: 33062134]
[16]
Ferroni P, Formica V, Roselli M, et al. Thromboembolic events in patients treated with anti-angiogenic drugs 2010; 8: 102-3.
[17]
Baethge C, Goldbeck-Wood S, Mertens S. SANRA—a scale for the quality assessment of narrative review articles. Res Integr Peer Rev 2019; 4(1): 5.
[http://dx.doi.org/10.1186/s41073-019-0064-8] [PMID: 30962953]
[18]
Carmeliet P, Jain RK. Molecular mechanisms and clinical applications of angiogenesis. Nature 2011; 473(7347): 298-307.
[http://dx.doi.org/10.1038/nature10144] [PMID: 21593862]
[19]
Touyz RM, Lang NN, Herrmann J, van den Meiracker AH, Danser AHJ. Recent advances in hypertension and cardiovascular toxicities with vascular endothelial growth factor inhibition. Hypertension 2017; 70(2): 220-6.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.117.08856] [PMID: 28630211]
[20]
Pucci G, Milan A, Paini A, Salvetti M, Cerasari A, Vaudo G. Acute blood pressure elevation associated with biological therapies for cancer: A focus on VEGF signaling pathway inhibitors. Expert Opin Biol Ther 2019; 19(5): 433-42.
[http://dx.doi.org/10.1080/14712598.2019.1594770] [PMID: 30888868]
[21]
Renni MJP, Cerqueira MH, Trugilho IA, Araujo MLC Junior, Marques MA, Koch HA. Mechanisms of venous thromboembolism in cancer: A literature review. J Vasc Bras 2017; 16(4): 308-13.
[http://dx.doi.org/10.1590/1677-5449.007817] [PMID: 29930665]
[22]
Kappers MHW, van Esch JHM, Sluiter W, Sleijfer S, Danser AHJ, van den Meiracker AH. Hypertension induced by the tyrosine kinase inhibitor sunitinib is associated with increased circulating endothelin-1 levels. Hypertension 2010; 56(4): 675-81.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.109.149690] [PMID: 20733093]
[23]
Pandey AK, Singhi EK, Arroyo JP, et al. Mechanisms of VEGF (vascular endothelial growth factor) inhibitor-associated hypertension and vascular disease. Hypertension 2018; 71(2): e1-8.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.117.10271] [PMID: 29279311]
[24]
Vassilakopoulou M, Mountzios G, Papamechael C, et al. Paclitaxel chemotherapy and vascular toxicity as assessed by flow-mediated and nitrate-mediated vasodilatation. Vascul Pharmacol 2010; 53(3-4): 115-21.
[http://dx.doi.org/10.1016/j.vph.2010.05.002] [PMID: 20470900]
[25]
Brinda BJ, Viganego F, Vo T, Dolan D, Fradley MG. Anti-VEGF-induced hypertension: A review of pathophysiology and treatment options. Curr Treat Options Cardiovasc Med 2016; 18(5): 33.
[http://dx.doi.org/10.1007/s11936-016-0452-z] [PMID: 26932588]
[26]
Agarwal M, Thareja N, Benjamin M, Akhondi A, Mitchell GD. Tyrosine kinase inhibitor-induced hypertension. Curr Oncol Rep 2018; 20(8): 65.
[http://dx.doi.org/10.1007/s11912-018-0708-8] [PMID: 29931399]
[27]
Vahdat LT, Layman R, Yardley DA, et al. Randomized phase II study of ramucirumab or icrucumab in combination with capecitabine in patients with previously treated locally advanced or metastatic breast cancer. Oncologist 2017; 22(3): 245-54.
[http://dx.doi.org/10.1634/theoncologist.2016-0265] [PMID: 28220020]
[28]
Miles D, Cameron D, Bondarenko I, et al. Bevacizumab plus paclitaxel versus placebo plus paclitaxel as first-line therapy for HER2-negative metastatic breast cancer (MERiDiAN): A double-blind placebo-controlled randomised phase III trial with prospective biomarker evaluation. Eur J Cancer 2017; 70: 146-55.
[http://dx.doi.org/10.1016/j.ejca.2016.09.024] [PMID: 27817944]
[29]
Bai ZG, Zhang ZT. A systematic review and meta-analysis on the effect of angiogenesis blockade for the treatment of gastric cancer. OncoTargets Ther 2018; 11: 7077-87.
[http://dx.doi.org/10.2147/OTT.S169484] [PMID: 30410364]
[30]
Veronese ML, Mosenkis A, Flaherty KT, et al. Mechanisms of hypertension associated with BAY 43-9006. J Clin Oncol 2006; 24(9): 1363-9.
[http://dx.doi.org/10.1200/JCO.2005.02.0503] [PMID: 16446323]
[31]
Abdel-Rahman O, Fouad M. Risk of mucocutaneous toxicities in patients with solid tumors treated with sunitinib: A critical review and meta analysis. Expert Rev Anticancer Ther 2015; 15(1): 129-41.
[http://dx.doi.org/10.1586/14737140.2015.985660] [PMID: 25482593]
[32]
Elice F, Jacoub J, Rickles FR, Falanga A, Rodeghiero F. Hemostatic complications of angiogenesis inhibitors in cancer patients. Am J Hematol 2008; 83(11): 862-70.
[http://dx.doi.org/10.1002/ajh.21277] [PMID: 18819092]
[33]
Nome ME, Euceda LR, Jabeen S, et al. Serum levels of inflammation‐related markers and metabolites predict response to neoadjuvant chemotherapy with and without bevacizumab in breast cancers. Int J Cancer 2020; 146(1): 223-35.
[http://dx.doi.org/10.1002/ijc.32638] [PMID: 31444972]
[34]
Sikov WM, Berry DA, Perou CM, et al. Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance). J Clin Oncol 2015; 33(1): 13-21.
[http://dx.doi.org/10.1200/JCO.2014.57.0572] [PMID: 25092775]
[35]
Sales ARK, Negrão MV, Testa L, et al. Chemotherapy acutely impairs neurovascular and hemodynamic responses in women with breast cancer. Am J Physiol Heart Circ Physiol 2019; 317(1): H1-H12.
[http://dx.doi.org/10.1152/ajpheart.00756.2018] [PMID: 31002284]
[36]
Jacob S, Pathak A, Franck D, et al. Early detection and prediction of cardiotoxicity after radiation therapy for breast cancer: The BACCARAT prospective cohort study. Radiat Oncol 2016; 11(1): 54.
[http://dx.doi.org/10.1186/s13014-016-0627-5] [PMID: 27056179]
[37]
Schlaak RA, SenthilKumar G, Boerma M, Bergom C. Advances in preclinical research models of radiation-induced cardiac toxicity. Cancers 2020; 12(2): 415.
[http://dx.doi.org/10.3390/cancers12020415] [PMID: 32053873]
[38]
Hufnagle JJ, Andersen SN, Maani EV. Radiation Therapy Induced Cardiac Toxicity. Treasure Island: StatPearls Publishing 2022; pp. 1-15.
[39]
Jia G, Aroor AR, Jia C, Sowers JR. Endothelial cell senescence in aging-related vascular dysfunction. Biochim Biophys Acta Mol Basis Dis 2019; 1865(7): 1802-9.
[http://dx.doi.org/10.1016/j.bbadis.2018.08.008] [PMID: 31109450]
[40]
Nagane M, Yasui H, Kuppusamy P, Yamashita T, Inanami O. DNA damage response in vascular endothelial senescence: Implication for radiation-induced cardiovascular diseases. J Radiat Res 2021; 62(4): 564-73.
[http://dx.doi.org/10.1093/jrr/rrab032] [PMID: 33912932]
[41]
Vallerio P, Sarno L, Stucchi M, et al. Long-term effects of radiotherapy on arterial stiffness in breast cancer women. Am J Cardiol 2016; 118(5): 771-6.
[http://dx.doi.org/10.1016/j.amjcard.2016.06.001] [PMID: 27392510]
[42]
Wennstig AK, Garmo H, Isacsson U, et al. The relationship between radiation doses to coronary arteries and location of coronary stenosis requiring intervention in breast cancer survivors. Radiat Oncol 2019; 14(1): 40.
[http://dx.doi.org/10.1186/s13014-019-1242-z] [PMID: 30845947]
[43]
Mast M, Reynders T, Heijenbrok M, et al. Tangential IMRT versus tomo therapy with and without breath-hold in left-sided whole breast irradiation. Acta Oncol 2016; 55(2): 240-3.
[http://dx.doi.org/10.3109/0284186X.2015.1046999] [PMID: 25997704]
[44]
Jacob S, Camilleri J, Derreumaux S, et al. Is mean heart dose a relevant surrogate parameter of left ventricle and coronary arteries exposure during breast cancer radiotherapy: A dosimetric evaluation based on individually-determined radiation dose (BACCARAT study). Radiat Oncol 2019; 14(1): 29.
[http://dx.doi.org/10.1186/s13014-019-1234-z] [PMID: 30732640]
[45]
Lee CH, Zhang JF, Yuan KSP, Wu ATH, Wu SY. Risk of cardiotoxicity induced by adjuvant anthracycline-based chemotherapy and radiotherapy in young and old Asian women with breast cancer. Strahlenther Onkol 2019; 195(7): 629-39.
[http://dx.doi.org/10.1007/s00066-019-01428-7] [PMID: 30690687]
[46]
Giordano P, Muggeo P, Delvecchio M, et al. Endothelial dysfunction and cardiovascular risk factors in childhood acute lymphoblastic leukemia survivors. Int J Cardiol 2017; 228: 621-7.
[http://dx.doi.org/10.1016/j.ijcard.2016.11.025] [PMID: 27889551]
[47]
Jones LW, Courneya KS, Mackey JR, et al. Cardiopulmonary function and age-related decline across the breast cancer survivorship continuum. J Clin Oncol 2012; 30(20): 2530-7.
[http://dx.doi.org/10.1200/JCO.2011.39.9014] [PMID: 22614980]
[48]
Naci H, Ioannidis JPA. Comparative effectiveness of exercise and drug interventions on mortality outcomes: Metaepidemiological study. Br J Sports Med 2015; 49(21): 1414-22.
[http://dx.doi.org/10.1136/bjsports-2015-f5577rep] [PMID: 26476429]
[49]
Whayne TF, Mukherjee D. Increased exercise favorably modifies coronary artery disease and peripheral arterial disease outcomes. Curr Vasc Pharmacol 2016; 14(5): 458-65.
[http://dx.doi.org/10.2174/1570161114999160719104936] [PMID: 27456103]
[50]
Eckstrom E, Neukam S, Kalin L, Wright J. Physical activity and healthy aging. Clin Geriatr Med 2020; 36(4): 671-83.
[http://dx.doi.org/10.1016/j.cger.2020.06.009] [PMID: 33010902]
[51]
Jakovljevic DG. Physical activity and cardiovascular aging: Physiological and molecular insights. Exp Gerontol 2018; 109: 67-74.
[http://dx.doi.org/10.1016/j.exger.2017.05.016] [PMID: 28546086]
[52]
Green DJ, Smith KJ. Effects of exercise on vascular function, structure, and health in humans. Cold Spring Harb Perspect Med 2018; 8(4): a029819.
[http://dx.doi.org/10.1101/cshperspect.a029819] [PMID: 28432115]
[53]
Seals DR, Nagy EE, Moreau KL. Aerobic exercise training and vascular function with ageing in healthy men and women. J Physiol 2019; 597(19): 4901-14.
[http://dx.doi.org/10.1113/JP277764] [PMID: 31077372]
[54]
Green DJ, Hopman MTE, Padilla J, Laughlin MH, Thijssen DHJ. Vascular adaptation to exercise in humans: Role of hemodynamic stimuli. Physiol Rev 2017; 97(2): 495-528.
[http://dx.doi.org/10.1152/physrev.00014.2016] [PMID: 28151424]
[55]
Chuong P, Wysoczynski M, Hellmann J. Do changes in innate immunity underlie the cardiovascular benefits of exercise? Front Cardiovasc Med 2019; 6(70): 70.
[http://dx.doi.org/10.3389/fcvm.2019.00070] [PMID: 31192231]
[56]
Le Jemtel TH, Samson R, Milligan G, Jaiswal A, Oparil S. Visceral adipose tissue accumulation and residual cardiovascular risk. Curr Hypertens Rep 2018; 20(9): 77.
[http://dx.doi.org/10.1007/s11906-018-0880-0] [PMID: 29992362]
[57]
Joyner MJ, Green DJ. Exercise protects the cardiovascular system: Effects beyond traditional risk factors. J Physiol 2009; 587(23): 5551-8.
[http://dx.doi.org/10.1113/jphysiol.2009.179432] [PMID: 19736305]
[58]
Laughlin MH, Newcomer SC, Bender SB. Importance of hemodynamic forces as signals for exercise-induced changes in endothelial cell phenotype. J Appl Physiol 2008; 104(3): 588-600.
[http://dx.doi.org/10.1152/japplphysiol.01096.2007] [PMID: 18063803]
[59]
Erkens R, Suvorava T, Kramer CM, Diederich LD, Kelm M, Cortese-Krott MM. Modulation of local and systemic heterocellular communication by mechanical forces: A role of endothelial nitric oxide synthase. Antioxid Redox Signal 2017; 26(16): 917-35.
[http://dx.doi.org/10.1089/ars.2016.6904] [PMID: 27927026]
[60]
Spence AL, Carter HH, Naylor LH, Green DJ. A prospective randomized longitudinal study involving 6 months of endurance or resistance exercise. Conduit artery adaptation in humans. J Physiol 2013; 591(5): 1265-75.
[http://dx.doi.org/10.1113/jphysiol.2012.247387] [PMID: 23247114]
[61]
Thijssen DHJ, Dawson EA, Black MA, Hopman MT, Cable NT, Green DJ. Brachial artery blood flow responses to different modalities of lower limb exercise. Med Sci Sports Exerc 2009; 41(5): 1072-9.
[http://dx.doi.org/10.1249/MSS.0b013e3181923957] [PMID: 19346980]
[62]
Schneider CM, Hsieh CC, Sprod LK, Carter SD, Hayward R. Exercise training manages cardiopulmonary function and fatigue during and following cancer treatment in male cancer survivors. Integr Cancer Ther 2007; 6(3): 235-41.
[http://dx.doi.org/10.1177/1534735407305871] [PMID: 17761636]
[63]
Pfannenstiel K, Hayward R. Effects of resistance exercise training on doxorubicin-induced cardiotoxicity. J Cardiovasc Pharmacol 2018; 71(6): 332-9.
[http://dx.doi.org/10.1097/FJC.0000000000000574] [PMID: 29521673]
[64]
Parry TL, Hayward R. Exercise protects against cancer-induced cardiac cachexia. Med Sci Sports Exerc 2018; 50(6): 1169-76.
[http://dx.doi.org/10.1249/MSS.0000000000001544] [PMID: 29315166]
[65]
van der Schoot GGF, Ormel HL, Westerink NDL, et al. Optimal timing of a physical exercise intervention to improve cardiorespiratory fitness. JACC: CardioOncology 2022; 4(4): 491-503.
[http://dx.doi.org/10.1016/j.jaccao.2022.07.006]
[66]
Bigaran A, Howden EJ, Foulkes S, et al. Prescribing exercise in early-stage breast cancer during chemotherapy: A simple periodized approach to align with the cyclic phases of chemotherapy. J Strength Cond Res 2022; 36(10): 2934-41.
[http://dx.doi.org/10.1519/JSC.0000000000003990] [PMID: 36135037]
[67]
Hall SE, Smuder AJ, Hayward R. Effects of calorie restriction and voluntary exercise on doxorubicin-induced cardiotoxicity. Integr Cancer Ther 2019; 18: 1534735419843999.
[http://dx.doi.org/10.1177/1534735419843999] [PMID: 30999765]
[68]
Beaudry RI, Liang Y, Boyton ST, et al. Meta-analysis of exercise training on vascular endothelial function in cancer survivors. Integr Cancer Ther 2018; 17(2): 192-9.
[http://dx.doi.org/10.1177/1534735418756193] [PMID: 29390904]
[69]
Kirkham AA, Shave RE, Bland KA, et al. Protective effects of acute exercise prior to doxorubicin on cardiac function of breast cancer patients: A proof-of-concept RCT. Int J Cardiol 2017; 245: 263-70.
[http://dx.doi.org/10.1016/j.ijcard.2017.07.037] [PMID: 28735755]
[70]
Lee K, Kang I, Mack WJ, et al. Effects of high-intensity interval training on vascular endothelial function and vascular wall thickness in breast cancer patients receiving anthracycline-based chemotherapy: A randomized pilot study. Breast Cancer Res Treat 2019; 177(2): 477-85.
[http://dx.doi.org/10.1007/s10549-019-05332-7] [PMID: 31236810]
[71]
Giallauria F, Maresca L, Vitelli A, et al. Exercise training improves heart rate recovery in women with breast cancer. Springerplus 2015; 4(1): 388.
[http://dx.doi.org/10.1186/s40064-015-1179-0] [PMID: 26240786]
[72]
Scott JM, Jones LW, Hornsby WE, et al. Cancer therapy-induced autonomic dysfunction in early breast cancer: Implications for aerobic exercise training. Int J Cardiol 2014; 171(2): e50-1.
[http://dx.doi.org/10.1016/j.ijcard.2013.11.113] [PMID: 24365613]
[73]
Ergun M, Eyigor S, Karaca B, Kisim A, Uslu R. Effects of exercise on angiogenesis and apoptosis-related molecules, quality of life, fatigue and depression in breast cancer patients. Eur J Cancer Care 2013; 22(5): 626-37.
[http://dx.doi.org/10.1111/ecc.12068] [PMID: 23731173]

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