{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:33:01Z","timestamp":1792787581475,"version":"4.5.0"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","funder":[{"name":"World Health Organization's World Cancer Research Fund","award":["IIG_2019_1948"],"award-info":[{"award-number":["IIG_2019_1948"]}]}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2023,2,14]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      Breast cancer survivors treated with anthracycline-based chemotherapy (AC) have increased risk of functional limitation and cardiac dysfunction. We conducted a 12-month randomized controlled trial in 104 patients with early-stage breast cancer scheduled for AC to determine whether 12 months of exercise training (ExT) could attenuate functional disability (primary end point), improve cardiorespiratory fitness (VO\n                      <jats:sub>2<\/jats:sub>\n                      peak), and prevent cardiac dysfunction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Women 40 to 75 years of age with stage I to III breast cancer scheduled for AC were randomized to 3 to 4 days per week aerobic and resistance ExT for 12 months (n=52) or usual care (UC; n=52). Functional measures were performed at baseline, at 4 weeks after AC (4 months), and at 12 months, comprising: (1) cardiopulmonary exercise testing to quantify VO\n                      <jats:sub>2<\/jats:sub>\n                      peak and functional disability (VO\n                      <jats:sub>2<\/jats:sub>\n                      peak \u226418.0 mL\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      \u00b7min\n                      <jats:sup>\u22121<\/jats:sup>\n                      ); (2) cardiac reserve (response from rest to peak exercise), quantified with exercise cardiac magnetic resonance measures to determine changes in left and right ventricular ejection fraction, cardiac output, and stroke volume; (3) standard-of-care echocardiography-derived resting left ventricular ejection fraction and global longitudinal strain; and (4) biochemistry (troponin and BNP [B-type natriuretic peptide]).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Among 104 participants randomized, greater study attrition was observed among UC participants (\n                      <jats:italic>P<\/jats:italic>\n                      =0.031), with 93 women assessed at 4 months (ExT, n=49; UC, n=44) and 87 women assessed at 12 months (ExT, n=49; UC, n=38). ExT attenuated functional disability at 4 months (odds ratio, 0.32 [95% CI, 0.11\u20130.94];\n                      <jats:italic>P<\/jats:italic>\n                      =0.03) but not at 12 months (odds ratio, 0.27 [95% CI, 0.06\u20131.12];\n                      <jats:italic>P<\/jats:italic>\n                      =0.07). In a per-protocol analysis, functional disability was prevented entirely at 12 months among participants adherent to ExT (ExT, 0% versus UC, 20%;\n                      <jats:italic>P<\/jats:italic>\n                      =0.005). Compared with UC at 12 months, ExT was associated with a net 3.5-mL\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      \u00b7min\n                      <jats:sup>\u22121<\/jats:sup>\n                      improvement in VO\n                      <jats:sub>2<\/jats:sub>\n                      peak that coincided with greater cardiac output, stroke volume, and left and right ventricular ejection fraction reserve (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.001 for all). There was no effect of ExT on resting measures of left ventricular function. Postchemotherapy troponin increased less in ExT than in UC (8-fold versus 16-fold increase;\n                      <jats:italic>P<\/jats:italic>\n                      =0.002). There were no changes in BNP in either group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      In women with early-stage breast cancer undergoing AC, 12 months of ExT did not attenuate functional disability, but provided large, clinically meaningful benefits on VO\n                      <jats:sub>2<\/jats:sub>\n                      peak and cardiac reserve.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Registration:<\/jats:title>\n                    <jats:p>\n                      URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.anzctr.org.au\/\">https:\/\/www.anzctr.org.au\/<\/jats:ext-link>\n                      ; Unique identifier: ACTRN12617001408370.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.122.062814","type":"journal-article","created":{"date-parts":[[2022,11,7]],"date-time":"2022-11-07T09:24:06Z","timestamp":1667813046000},"page":"532-545","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":142,"title":["Exercise for the Prevention of Anthracycline-Induced Functional Disability and Cardiac Dysfunction: The BREXIT Study"],"prefix":"10.1161","volume":"147","author":[{"given":"Stephen J.","family":"Foulkes","sequence":"first","affiliation":[{"name":"Sports Cardiology (S.J.F., K.J., A.M.M., L.W., B.T.C., A.L., L.B., I.W., A.L.G.), Baker Heart and Diabetes Institute, Melbourne, VIC, Australia."},{"name":"Faculty of Nursing, College of Health Sciences, University of Alberta, Edmonton, Canada (M.J.H., S.J.F.)."},{"name":"Baker Department of Cardiometabolic Health (S.J.F., E.J.H., A.L.G.), University of Melbourne, Parkville, VIC, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6657-4395","authenticated-orcid":true,"given":"Erin J.","family":"Howden","sequence":"additional","affiliation":[{"name":"Human Integrative Physiology (E.J.H., L.B., I.W.), Baker Heart and Diabetes Institute, Melbourne, VIC, Australia."},{"name":"Baker Department of Cardiometabolic Health (S.J.F., E.J.H., A.L.G.), University of Melbourne, Parkville, VIC, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Haykowsky","sequence":"additional","affiliation":[{"name":"Faculty of Nursing, College of Health Sciences, University of Alberta, Edmonton, Canada (M.J.H., S.J.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoland","family":"Antill","sequence":"additional","affiliation":[{"name":"Cabrini Health, Melbourne, VIC, Australia (Y.A.)."},{"name":"Faculty of Medicine, Dentistry and Health Sciences, Monash University, Melbourne, VIC, Australia (Y.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agus","family":"Salim","sequence":"additional","affiliation":[{"name":"Epidemiology (A.S.), Baker Heart and Diabetes Institute, Melbourne, VIC, Australia."},{"name":"Melbourne School of Population and Global Health (A.S.), University of Melbourne, Parkville, VIC, Australia."},{"name":"School of Mathematics and Statistics (A.S.), University of Melbourne, Parkville, VIC, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie S.","family":"Nightingale","sequence":"additional","affiliation":[{"name":"Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (S.S.N., S.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherene","family":"Loi","sequence":"additional","affiliation":[{"name":"Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (S.S.N., S.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piet","family":"Claus","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, KU Leuven, Belgium (P.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristel","family":"Janssens","sequence":"additional","affiliation":[{"name":"Sports Cardiology (S.J.F., K.J., A.M.M., L.W., B.T.C., A.L., L.B., I.W., A.L.G.), Baker Heart and Diabetes Institute, Melbourne, VIC, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy M.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Sports Cardiology (S.J.F., K.J., A.M.M., L.W., B.T.C., A.L., L.B., I.W., A.L.G.), Baker Heart and Diabetes Institute, Melbourne, VIC, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah","family":"Wright","sequence":"additional","affiliation":[{"name":"Sports Cardiology (S.J.F., K.J., A.M.M., L.W., B.T.C., A.L., L.B., I.W., A.L.G.), Baker Heart and Diabetes Institute, Melbourne, VIC, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben T.","family":"Costello","sequence":"additional","affiliation":[{"name":"Sports Cardiology (S.J.F., K.J., A.M.M., L.W., B.T.C., A.L., L.B., I.W., A.L.G.), Baker Heart and Diabetes Institute, Melbourne, VIC, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7771-0620","authenticated-orcid":true,"given":"Anniina","family":"Lindqvist","sequence":"additional","affiliation":[{"name":"Sports Cardiology (S.J.F., K.J., A.M.M., L.W., B.T.C., A.L., L.B., I.W., A.L.G.), Baker Heart and Diabetes Institute, Melbourne, VIC, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Burnham","sequence":"additional","affiliation":[{"name":"Human Integrative Physiology (E.J.H., L.B., I.W.), Baker Heart and Diabetes Institute, Melbourne, VIC, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imogen","family":"Wallace","sequence":"additional","affiliation":[{"name":"Sports Cardiology (S.J.F., K.J., A.M.M., L.W., B.T.C., A.L., L.B., I.W., A.L.G.), Baker Heart and Diabetes Institute, Melbourne, VIC, Australia."},{"name":"Human Integrative Physiology (E.J.H., L.B., I.W.), Baker Heart and Diabetes Institute, Melbourne, VIC, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9897-1598","authenticated-orcid":true,"given":"Robin M.","family":"Daly","sequence":"additional","affiliation":[{"name":"Institute for Physical Activity and Nutrition, Deakin University, Melbourne, VIC, Australia (R.M.D., S.F.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0202-9619","authenticated-orcid":true,"given":"Steve F.","family":"Fraser","sequence":"additional","affiliation":[{"name":"Institute for Physical Activity 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