Cardiorespiratory fitness (VO2peak) is a clinical endpoint of immense importance following a diagnosis of breast cancer (BC). VO2peak is a strong predictor of overall quality of life, fatigue and other patient-reported outcomes (PROs) among women with early-stage BC. Furthermore, VO2peak is also strongly correlated with biomarkers of BC prognosis and cardiovascular disease. Finally, VO2peak and other measures of cardiorespiratory fitness are well-established predictors of cardiovascular and all-cause mortality in noncancer populations while regular exercise (a major determinant of VO2peak) is associated with a 50% reduction in the risk of mortality, relative to inactive women, following a BC diagnosis. Clearly, interventions that optimally improve VO2peak stand to have considerable clinical benefit for women with BC. Moderate-intensity aerobic training is associated with statistically significant but modest improvements in VO2peak among women with early BC. Based on this data, the American Cancer Society and Institute of Medicine issued guidelines recommending that all cancer patients should exercise e5 days/week for e30 minutes at a moderate intensity. However, no study to date has investigated the level and format of aerobic training that produces optimal improvements in VO2peak and other endpoints in any cancer population. We propose a prospective, three-arm, randomized trial to compare the effects of two aerobic training interventions relative to an attention-control group among early-stage BC patients who have completed primary cancer therapy. This grant will have the following primary and secondary aims: Primary aim: To compare the effect of high-intensity training to moderate-intensity training, relative to attention-control, on VO2peak. Secondary aims: (1) to examine the effects on physiological mediators of VO2peak, (2) To compare the effects on PROs, (3) to compare the effects on biomarkers of BC recurrence and mortality (i.e., metabolic homeostasis and systemic inflammation). This study will address several fundamental but, currently unanswered questions regarding the role of exercise training in the management of breast cancer. Information gained from this clinical trial will inform the design in future-planned studies further investigating the role of exercise training across the breast cancer survivorship continuum. Finally, the mechanistic findings will provide insight into how to refine exercise training interventions to maximize improvements in VO2peak and associated outcomes.

Public Health Relevance

PUBLIC HEATH STATEMENT Cardiorespiratory fitness is a clinical endpoint of immense importance following a diagnosis of breast cancer. No study to date has investigated the level and format of aerobic training that produces optimal improvements in VO2peak and other endpoints in any cancer population. This project will compare the effects of two aerobic training interventions on changes in cardiorespiratory fitness in 174 breast cancer patients following the completion of primary therapy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA142566-03
Application #
8215895
Study Section
Behavioral Medicine, Interventions and Outcomes Study Section (BMIO)
Program Officer
Alfano, Catherine M
Project Start
2010-04-01
Project End
2016-01-31
Budget Start
2012-02-01
Budget End
2013-01-31
Support Year
3
Fiscal Year
2012
Total Cost
$172,950
Indirect Cost
$62,085
Name
Duke University
Department
Surgery
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Scott, Jessica M; Jones, Lee W; Hornsby, Whitney E et al. (2014) Cancer therapy-induced autonomic dysfunction in early breast cancer: implications for aerobic exercise training. Int J Cardiol 171:e50-1
Jones, Lee W; Douglas, Pamela S; Khouri, Michel G et al. (2014) Safety and efficacy of aerobic training in patients with cancer who have heart failure: an analysis of the HF-ACTION randomized trial. J Clin Oncol 32:2496-502
Hornsby, Whitney E; Douglas, Pamela S; West, Miranda J et al. (2014) Safety and efficacy of aerobic training in operable breast cancer patients receiving neoadjuvant chemotherapy: a phase II randomized trial. Acta Oncol 53:65-74
Tonorezos, Emily S; Jones, Lee W (2013) Energy balance and metabolism after cancer treatment. Semin Oncol 40:745-56
Scott, Jessica M; Koelwyn, Graeme J; Hornsby, Whitney E et al. (2013) Exercise therapy as treatment for cardiovascular and oncologic disease after a diagnosis of early-stage cancer. Semin Oncol 40:218-28
Maddocks, Matthew; Jones, Lee W; Wilcock, Andrew (2013) Immunological and hormonal effects of exercise: implications for cancer cachexia. Curr Opin Support Palliat Care 7:376-82
Jones, Lee W; Alfano, Catherine M (2013) Exercise-oncology research: past, present, and future. Acta Oncol 52:195-215
Scott, Jessica M; Lakoski, Susan; Mackey, John R et al. (2013) The potential role of aerobic exercise to modulate cardiotoxicity of molecularly targeted cancer therapeutics. Oncologist 18:221-31
Dolinsky, Vernon W; Rogan, Kyle J; Sung, Miranda M et al. (2013) Both aerobic exercise and resveratrol supplementation attenuate doxorubicin-induced cardiac injury in mice. Am J Physiol Endocrinol Metab 305:E243-53
Lakoski, Susan G; Barlow, Carolyn E; Koelwyn, Graeme J et al. (2013) The influence of adjuvant therapy on cardiorespiratory fitness in early-stage breast cancer seven years after diagnosis: the Cooper Center Longitudinal Study. Breast Cancer Res Treat 138:909-16

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