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Does Physical Activity During Cancer Treatment Preserve Exercise Capacity?

2023; Lippincott Williams & Wilkins; Volume: 147; Issue: 7 Linguagem: Inglês

10.1161/circulationaha.122.063192

1524-4539

Wendy Bottinor, W. Gregory Hundley,

Physical Activity and Health

HomeCirculationVol. 147, No. 7Does Physical Activity During Cancer Treatment Preserve Exercise Capacity? Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBDoes Physical Activity During Cancer Treatment Preserve Exercise Capacity? Wendy Bottinor and W. Gregory Hundley Wendy BottinorWendy Bottinor Correspondence to: Wendy Bottinor, MD, MSCI, Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Gateway Building, 1200 E Marshall St, Richmond, VA 23298. Email E-mail Address: [email protected] Department of Internal Medicine, Division of Cardiovascular Medicine, Pauley Heart Center, Virginia Commonwealth University, Richmond. and W. Gregory HundleyW. Gregory Hundley https://orcid.org/0000-0002-2433-8853 Department of Internal Medicine, Division of Cardiovascular Medicine, Pauley Heart Center, Virginia Commonwealth University, Richmond. Originally published13 Feb 2023https://doi.org/10.1161/CIRCULATIONAHA.122.063192Circulation. 2023;147:546–548This article is a commentary on the followingExercise for the Prevention of Anthracycline-Induced Functional Disability and Cardiac Dysfunction: The BREXIT StudyRandomized Controlled Trial of a Smartphone-Based Intervention to Enhance 6-Minute Walk Distance During Breast Cancer Treatment: The SMART-BREAST TrialCardiovascular disease and cancer are leading causes of death globally. Although traditionally considered distinct disease processes, numerous links between the 2 entities have been identified. Physical activity is one of these links. Individuals achieving recommended physical activity targets experience a 40% reduction in cardiovascular disease mortality,1 and physical activity helps prevent breast, prostate, colon, and endometrial cancer.2Physical inactivity, exercise intolerance, dyspnea, and fatigue that affect health-related quality of life are emerging concerns for health care providers treating patients with cancer. In women with breast cancer, receipt of potentially cardiotoxic treatments, such as anthracyclines, can promote exercise intolerance. This is frequently manifested by difficulty in performing activities of daily living and is quantified through assessment of peak oxygen consumption (peak VO2) and declines in 6-minute walk distance (6MWD). Up to 46% of breast cancer survivors experience low cardiorespiratory fitness (peak VO2 ≤18 mL/kg per minute).3 Compared with healthy controls, 6MWD is, on average, 103 meters lower among breast cancer survivors.4Articles, see p 532 and p 614This issue of Circulation features 2 studies that examine the potential benefit of performing physical activity during receipt of anthracycline-based chemotherapy for breast cancer. In one randomized clinical trial, Foulkes et al5 examined the usefulness of a 12-month exercise intervention in preserving exercise capacity among women with breast cancer receiving anthracycline-based chemotherapy. A total of 104 participants were randomized to either usual care, which consisted of encouragement and referral to written recommendations for physical activity, or an individualized multicomponent exercise program consisting of endurance, tempo, and both high-intensity interval and resistance training. This exercise program included 12 weeks of directly supervised exercise followed by 14 weeks of semisupervised exercise, and concluded with 26 weeks of maintenance that included remote support through weekly messages and 6 face-to-face review appointments. The primary outcome, prevention of a peak VO2 ≤18 mL/kg per minute at 12 months, was not significantly different between the 2 groups. However, there was a modest improvement in peak VO2 from baseline to 12 months (+2.0 mL/kg per minute) in the intervention group compared with a decline in peak VO2 (−1.5 mL/kg per minute) in the usual care group (P<0.001). Also at this 12-month time point, there were no differences in resting left ventricular ejection fraction, global longitudinal strain, or brain natriuretic peptide among individuals within the 2 groups. However, there was improvement in cardiac reserve (as measured by changes in cardiac output, left ventricular stroke volume and ejection fraction, and right ventricular ejection fraction from rest to peak exercise; P<0.001) in those randomized to the intervention. Troponin increase at 4 months was significantly lower (P=0.002) among those randomized to the exercise program.In contrast to the directly supervised intervention performed by Foulkes et al,5 Murphy et al6 used smartphone technology to encourage physical activity among women with breast cancer. Murphy et al6 randomized 103 individuals to either standard of care or a multifaceted smartphone-based intervention. The primary outcome of this study was the 6MWD, a validated tool for predicting morbidity and mortality among individuals with cardiopulmonary disease that also reflects the ability to perform activities of daily living.7 Whereas participants who received standard of care did not demonstrate a significant increase in 6MWD, among those who received the smartphone application, 6MWD increased by 46 meters (P<0.001).The results of these 2 studies highlight the potential benefit of exercise training and increased activity to preserve exercise tolerance during breast cancer therapy. Exercise intolerance in the setting of breast cancer treatment stems from adverse effects on multiple biological systems. In the heart, anthracycline therapy can promote myocyte necrosis, fibrosis, inflammation, and mitochondrial disruption.8 Vascular toxicity, including endothelial dysfunction and increased aortic stiffness, can also occur.9,10 Skeletal muscle toxicity leads to decreased muscle mass and increased intermuscular fat.11 Deleterious metabolic changes such as insulin resistance have also been associated with anthracycline therapy.12As shown in the Figure, exercise may counteract several of the untoward effects of breast cancer therapies that contribute to exercise intolerance. Exercise training is associated with increased cardiac output, cardiac mitochondrial biogenesis, reduced inflammation, increased vascular density, improved vasodilatory responses, reduced aortic stiffness, decreased myosteatosis, and improved insulin sensitivity.13–15Download figureDownload PowerPointFigure. Factors influencing exercise tolerance among cancer survivors. Left, Potential multisystem consequences of anthracycline therapy that contribute to exercise intolerance. Right, Potential multisystem benefits of exercise training. Created with BioRender.com.Whereas these 2 studies address the importance of combating exercise intolerance in breast cancer survivors, there are several limitations that should be considered. First, attrition rates at 12 months exceeded 10%. Identifying programs to enhance continued participation for these patients would be helpful. Second, the generalizability of these interventions to populations with a high burden of cardiovascular comorbidities or challenges related to social determinants of health is not defined. For example, socioeconomic factors that may influence ease of transportation for frequent visits to an exercise facility represent important considerations. In addition, for those using smartphone-based applications, logistical issues regarding accessibility to internet and cellular-based interventions across diverse communities will need to be examined.These 2 research teams are to be congratulated for addressing one of the most common adverse conditions associated with breast cancer treatment—exercise intolerance. These very early results suggest the potential for increasing activity and aerobic and strength training during the several months during which women with breast cancer receive potentially cardiotoxic chemotherapy. These studies also highlight opportunities for future research endeavors. Topics for further exploration include behavioral interventions to promote regular participation in exercise, home-based interventions, and engagement of more diverse patient communities. These efforts will help ensure that patients not only survive but thrive after cancer therapy.Article InformationSources of FundingThis publication was supported by Clinical and Translational Science Award KL2TR002648 from the National Center for Advancing Translational Sciences, To-morrow's Research Fund St Baldrick's scholar award 636214, American Heart Association award 19CDA34760181, and National Institutes of Health awards 1R01HL118740, 1R01CA199167, and R21CA226960-01A1. The contents are solely the responsibility of the authors and do not necessarily represent the official views of St Baldrick's Foundation, the American Heart Association, or the National Institutes of Health.Disclosures None.FootnotesThis article is part of the Science Goes Red™ collection. Science Goes Red™ is an initiative of Go Red for Women®, the American Heart Association's global movement to end heart disease and stroke in women.The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.For Sources of Funding and Disclosures, see page 548.Circulation is available at www.ahajournals.org/journal/circCorrespondence to: Wendy Bottinor, MD, MSCI, Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Gateway Building, 1200 E Marshall St, Richmond, VA 23298. Email wendy.bottinor@vcuhealth.orgReferences1. Piercy KL, Troiano RP. Physical activity guidelines for Americans from the US Department of Health and Human Services.CircCardiovascQual Outcomes. 2018; 11:e005263. doi: 10.1161/CIRCOUTCOMES.118.005263LinkGoogle Scholar2. Rock CL, Thomson C, Gansler T, Gapstur SM, McCullough ML, Patel AV, Andrews KS, Bandera EV, Spees CK, Robien K, et al. American Cancer Society guideline for diet and physical activity for cancer prevention.CA Cancer J Clin. 2020; 70:245–271. doi: 10.3322/caac.21591CrossrefMedlineGoogle Scholar3. Jones LW, Haykowsky M, Peddle CJ, Joy AA, Pituskin EN, Tkachuk LM, Courneya KS, Slamon DJ, Mackey JR. Cardiovascular risk profile of patients with HER2/neu-positive breast cancer treated with anthracycline-taxane-containing adjuvant chemotherapy and/or trastuzumab.Cancer Epidemiol BiomarkersPrev. 2007; 16:1026–1031. doi: 10.1158/1055-9965.EPI-06-0870CrossrefMedlineGoogle Scholar4. But-Hadzic J, Dervisevic M, Karpljuk D, Videmsek M, Dervisevic E, Paravlic A, Hadzic V, Tomazin K. Six-minute walk distance in breast cancer survivors: a systematic review with meta-analysis.Int J Environ Res Public Health. 2021; 18:2591. doi: 10.3390/ijerph18052591CrossrefMedlineGoogle Scholar5. Foulkes SJ, Howden EJ, Haykowsky MJ, Antill Y, Salim A, Nightingale SS, Loi S, Claus P, Janssens K, Mitchell AM, et al. Exercise for the prevention of anthracycline-induced functional disability and cardiac dysfunction: the BREXIT study.Circulation. 2023; 147:532–545. doi: 10.1161/CIRCULATIONAHA.122.062814LinkGoogle Scholar6. Murphy AC, Farouque O, Koshy AN, Yeo B, Dick R, Nadurata V, Roccisano L, Reid C, Yudi MB. Randomized controlled trial of a smartphone-based intervention to enhance 6-minute walk distance during breast cancer treatment: the SMART-BREAST trial.Circulation. 2023; 147:614–616. doi: 10.1161/CIRCULATIONAHA.122.062946LinkGoogle Scholar7. Cahalin LP, Mathier MA, Semigran MJ, Dec GW, DiSalvo TG. The six-minute walk test predicts peak oxygen uptake and survival in patients with advanced heart failure.Chest. 1996; 110:325–332. doi: 10.1378/chest.110.2.325CrossrefMedlineGoogle Scholar8. Narezkina A, Narayan HK, Zemljic-Harpf AE. Molecular mechanisms of anthracycline cardiovascular toxicity.ClinSci. 2021; 135:1311–1332. doi: 10.1042/CS20200301CrossrefGoogle Scholar9. Campia U, Moslehi JJ, Amiri-Kordestani L, Barac A, Beckman JA, Chism DD, Cohen P, Groarke JD, Herrmann J, Reilly CM, et al. Cardio-oncology: vascular and metabolic perspectives: a scientific statement from the American Heart Association.Circulation. 2019; 139:e579–e602doi: 10.1161/CIR.0000000000000641LinkGoogle Scholar10. Chaosuwannakit N, D'Agostino R, Hamilton CA, Lane KS, Ntim WO, Lawrence J, Melin SA, Ellis LR, Torti FM, Little WC, et al. Aortic stiffness increases upon receipt of anthracycline chemotherapy.J ClinOncol. 2010; 28:166–172. doi: 10.1200/JCO.2009.23.8527CrossrefGoogle Scholar11. Reding KW, Brubaker P, D'Agostino R, Kitzman DW, Nicklas B, Langford D, Grodesky M, Hundley WG. Increased skeletal intermuscular fat is associated with reduced exercise capacity in cancer survivors: a cross-sectional study.Cardio-Oncology. 2019; 5:3. doi: 10.1186/s40959-019-0038-5CrossrefMedlineGoogle Scholar12. Russo M, Della Sala A, Tocchetti CG, Porporato PE, Ghigo A. Metabolic aspects of anthracycline cardiotoxicity.Curr Treat Options Oncol. 2021; 22:18. doi: 10.1007/s11864-020-00812-1CrossrefMedlineGoogle Scholar13. Nystoriak MA, Bhatnagar A. Cardiovascular effects and benefits of exercise.Front CardiovascMed. 2018; 5:135. doi: 10.3389/fcvm.2018.00135CrossrefMedlineGoogle Scholar14. Ramírez-Vélez R, Ezzatvar Y, Izquierdo M, García-Hermoso A. Effect of exercise on myosteatosis in adults: a systematic review and meta-analysis.J ApplPhysiol. 2021; 130:245–255. doi: 10.1152/japplphysiol.00738.2020CrossrefMedlineGoogle Scholar15. Brinkley TE, Leng I, Bailey MJ, Houston DK, Hugenschmidt CE, Nicklas BJ, Hundley WG. Effects of exercise and weight loss on proximal aortic stiffness in older adults with obesity.Circulation. 2021; 144:684–693. doi: 10.1161/circulationaha.120.051943LinkGoogle Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesExercise for the Prevention of Anthracycline-Induced Functional Disability and Cardiac Dysfunction: The BREXIT StudyStephen J. Foulkes, et al. Circulation. 2023;147:532-545Randomized Controlled Trial of a Smartphone-Based Intervention to Enhance 6-Minute Walk Distance During Breast Cancer Treatment: The SMART-BREAST TrialAlexandra C. Murphy, et al. Circulation. 2023;147:614-616 February 14, 2023Vol 147, Issue 7 Advertisement Article InformationMetrics © 2023 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.122.063192PMID: 36780389 Originally publishedFebruary 13, 2023 KeywordsEditorialsdrug therapyexerciseneoplasmsPDF download Advertisement SubjectsCardio-Oncology