Scott, Jessica M.

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.

12081 Background: A common conception is that exercise training is cardioprotective for patients with breast cancer receiving adjuvant chemotherapy, but evidence to support this assertion is limited. This study aims to evaluate the effect of exercise training during adjuvant chemotherapy for breast cancer on long-term structural and functional cardiac outcomes. Methods: This is a follow-up study of two previously performed randomized studies in breast cancer patients; the PACT (N = 204) and PACES (N = 230) study. Cardiac outcomes, including extracellular volume fraction (ECV), left ventricular ejection fraction (LVEF) on cardiac MRI and global longitudinal strain (GLS) on echocardiography, were evaluated in patients allocated to moderate-to high-intensity exercise and non-exercise controls using linear and logistic regression models, adjusted for relevant confounders. Additionally, we explored the influence of self-reported PA during chemotherapy on cardiac outcomes, regardless of treatment allocation. Results: In total, 185 breast cancer survivors were included (mean age 58.9±7.8 years, mean time since treatment 8.5±1.1 years). Mean ECV was 25.3±2.5 in the control group and 24.6±2.8 in the exercise group. Mean LVEF was borderline normal in both (54.6±4.9 and 53.0±7.8) with an LVEF < 50% of 17.1% and 27.8% in control and exercise group, respectively. Compared to control, no significant effect of exercise during chemotherapy on ECV (β = -0.61, 95%CI: -1.55;0.32) or on abnormal ECV (OR = 0.80, 95%CI: 0.26;2.45) was found. Native T1 was statistically significantly lower in the exercise group compared to control (β = -16.75%CI: -31.5 ;-1.93). The odds of having an abnormal native T1 appeared lower in the exercise group (OR 0.58, 95%CI: 0.28;1.17). We found no benefit of exercise for LVEF or GLS (β = -1.82, 95%CI: -4.06;0.42 and β = 0.21, 95%CI: -0.87;1.28), nor on the likelihood of having an abnormal LVEF or GLS (OR = 1.78, 95%CI: 0.79;4.16); OR = 1.21, 95%CI: 0.56;2.63), respectively. Higher self-reported physical activity levels during chemotherapy tended to be associated with better cardiac outcomes. Conclusions: Exercise training during chemotherapy was not associated with long-term cardioprotection in patients with early-stage breast cancer. The high prevalence of cardiac abnormalities years post-chemotherapy suggests the need to include cardiac assessment in long-term follow-up programs for breast cancer survivors and calls for more research on cardioprotective measures during adjuvant chemotherapy, including alternative exercise dosing regimens and pharmacological adjuncts. Clinical trial information: NTR7247.

Abstract Up to 85% of adult cancer survivors and 99% of adult survivors of childhood cancer live with an accumulation of chronic conditions, frailty, and/or cognitive impairments resulting from cancer and its treatment. Thus, survivors often show an accelerated development of multiple geriatric syndromes and need therapeutic interventions. To advance progress in this area, the National Cancer Institute convened the second of 2 think tanks under the auspices of the Cancer and Accelerated Aging: Advancing Research for Healthy Survivors initiative. Experts assembled to share evidence of promising strategies to prevent, slow, or reverse the aging consequences of cancer and its treatment. The meeting identified research and resource needs, including geroscience-guided clinical trials; comprehensive assessments of functional, cognitive, and psychosocial vulnerabilities to assess and predict age-related outcomes; preclinical and clinical research to determine the optimal dosing for behavioral (eg, diet, exercise) and pharmacologic (eg, senolytic) therapies; health-care delivery research to evaluate the efficacy of integrated cancer care delivery models; optimization of intervention implementation, delivery, and uptake; and patient and provider education on cancer and treatment-related late and long-term adverse effects. Addressing these needs will expand knowledge of aging-related consequences of cancer and cancer treatment and inform strategies to promote healthy aging of cancer survivors.