Exercise for the Prevention of Anthracycline-Induced Functional Disability and Cardiac Dysfunction: The BREXIT Study. Issue 7 (7th November 2022)

• Record Type: Journal Article
• Authors: Foulkes, Stephen J.; Howden, Erin J.; Haykowsky, Mark J.; Antill, Yoland; Salim, Agus; Nightingale, Sophie S.; Loi, Sherene; Claus, Piet; Janssens, Kristel; Mitchell, Amy M.; Wright, Leah; Costello, Ben T.; Lindqvist, Anniina; Burnham, Lauren; Wallace, Imogen; Daly, Robin M.; Fraser, Steve F.; La Gerche, André
• Is Part Of: Circulation. Volume 147:Issue 7(2023)
• Page Start: 532
• Page End: 545
• Publication Date: 2022-11-07
• Subjects: cancer -- cardiorespiratory fitness -- cardiotoxicity -- drug therapy; Blood -- Circulation -- Periodicals; Cardiovascular system -- Periodicals; Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; Blood Circulation; Cardiovascular System; Vascular Diseases; 616.1
• DOI: 10.1161/CIRCULATIONAHA.122.062814
• Languages: English
• ISSNs: 0009-7322

Abstract

Abstract : Background: 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 (VO2 peak), and prevent cardiac dysfunction. Methods: 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 VO2 peak and functional disability (VO2 peak ≤18.0 mL·kg −1 ·min −1 ); (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]). Results: Among 104 participants randomized, greater study attrition was observed among UC participants ( P =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, 0.11–0.94]; P =0.03) but not at 12 months (odds ratio, 0.27 [95% CI, 0.06–1.12]; P =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%; P =0.005). Compared with UC at 12 months, ExT was associated with a net 3.5-mL·kg −1 ·min −1 improvement in VO2 peak that coincided with greater cardiac output, stroke volume, and left and right ventricular ejection fraction reserve ( P <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; P =0.002). There were no changes in BNP in either group. Conclusions: 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 VO2 peak and cardiac reserve. Registration: URL: https://www.anzctr.org.au/ ; Unique identifier: ACTRN12617001408370.