Effects of exercise during chemotherapy for breast cancer on long-term cardiovascular toxicity

Abstract

Objective: Animal data suggest that exercise during chemotherapy is cardioprotective, but clinical evidence to support this is limited. This study evaluated the effect of exercise during chemotherapy for breast cancer on long-term cardiovascular toxicity.

Methods: This is a follow-up study of two previously performed randomised trials in patients with breast cancer allocated to exercise during chemotherapy or non-exercise controls. Cardiac imaging parameters, including T1 mapping (native T1, extracellular volume fraction (ECV)), left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS), cardiorespiratory fitness, and physical activity levels, were acquired 8.5 years post-treatment.

Results: In total, 185 breast cancer survivors were included (mean age 58.9±7.8 years), of whom 99% and 18% were treated with anthracyclines and trastuzumab, respectively. ECV and Native T1 were 25.3%±2.5% and 1026±51 ms in the control group, and 24.6%±2.8% and 1007±44 ms in the exercise group, respectively. LVEF was borderline normal in both groups, with an LVEF<50% prevalence of 22.5% (n=40/178) in all participants. Compared with control, native T1 was statistically significantly lower in the exercise group (β=-20.16, 95% CI -35.35 to -4.97). We found no effect of exercise on ECV (β=-0.69, 95% CI -1.62 to 0.25), LVEF (β=-1.36, 95% CI -3.45 to 0.73) or GLS (β=0.31, 95% CI -0.76 to 1.37). Higher self-reported physical activity levels during chemotherapy were significantly associated with better native T1 and ECV.

Conclusions: In long-term breast cancer survivors, exercise and being more physically active during chemotherapy were associated with better structural but not functional cardiac parameters. The high prevalence of cardiac dysfunction calls for additional research on cardioprotective measures, including alternative exercise regimens.

Trial registration number: NTR7247.

Keywords: echocardiography; heart failure; magnetic resonance imaging.

Figure 1

Original PACT and PACES study, and the follow-up Pact-Paces-Heart study. PACES, Physical Exercise during Adjuvant Chemotherapy Effectiveness Study; PACT, Physical Activity during Cancer Treatment.

Figure 2

Flow chart of participants in the Pact-Paces-Heart study. FU, follow-up; PACES, Physical Exercise during Adjuvant Chemotherapy Effectiveness Study; PACT, Physical Activity during Cancer Treatment.

Figure 3

Relationship between structural and functional cardiac parameters using cardiac MRI. In (A, B), the relationship between ECV and native T1 and LVEF is depicted, respectively. The grey lines indicate the thresholds used for cut-off. In (C), the presence and absence of LGE in patients with normal and impaired LVEF is described. Here, each woman symbol represents five participants. ECV, extracellular volume; LGE, late gadolinium enhancement; LVEF, left ventricular ejection fraction.