• Mitchell, Amy M.
• Wright, Leah
• Foulkes, Stephen J.
• Lindqvist, Anniina
• Costello, Ben T.
• La Gerche, Andre
• Daly, Robin M.
• Loi, Sherene
• Nightingale, Sophie S.
• Burnham, Lauren
• Janssens, Kristel
• Wallace, Imogen
• Claus, Piet
• Haykowsky, Mark J.
• Salim, Agus
• Antill, Yoland

Abstract

<jats:sec><jats:title>Background:</jats:title><jats:p>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<jats:sub>2</jats:sub>peak), and prevent cardiac dysfunction.</jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p>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<jats:sub>2</jats:sub>peak and functional disability (VO<jats:sub>2</jats:sub>peak ≤18.0 mL·kg<jats:sup>−1</jats:sup>·min<jats:sup>−1</jats:sup>); (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]).</jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p>Among 104 participants randomized, greater study attrition was observed among UC participants (<jats:italic>P</jats:italic>=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];<jats:italic>P</jats:italic>=0.03) but not at 12 months (odds ratio, 0.27 [95% CI, 0.06–1.12];<jats:italic>P</jats:italic>=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%;<jats:italic>P</jats:italic>=0.005). Compared with UC at 12 months, ExT was associated with a net 3.5-mL·kg<jats:sup>−1</jats:sup>·min<jats:sup>−1</jats:sup>improvement in VO<jats:sub>2</jats:sub>peak that coincided with greater cardiac output, stroke volume, and left and right ventricular ejection fraction reserve (<jats:italic>P</jats:italic>&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;<jats:italic>P</jats:italic>=0.002). There were no changes in BNP in either group.</jats:p></jats:sec><jats:sec><jats:title>Conclusions:</jats:title><jats:p>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<jats:sub>2</jats:sub>peak and cardiac reserve.</jats:p></jats:sec><jats:sec><jats:title>Registration:</jats:title><jats:p>URL:<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>; Unique identifier: ACTRN12617001408370.</jats:p></jats:sec>

Topics

• laser emission spectroscopy
• size-exclusion chromatography
• chemical ionisation