Grant Number:	1R01CA142566-01A1 Interpret this number
Primary Investigator:	Jones, Lee
Organization:	Duke University
Project Title:	Randomized Trial of Optimal Type of Aerobic Training in Breast Cancer
Fiscal Year:	2010

DESCRIPTION (provided by applicant): 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.




Mechanisms of Exercise Intolerance Across the Breast Cancer Continuum: A Pooled Analysis of Individual Patient Data.
Authors: Scott J.M. , Lee J. , Michalski M.G. , Batch K. , Simpson A.L. , Peoples J. , Lee C.P. , Harrison J.N. , Yu A.F. , Sasso J.P. , et al. .
Source: Medicine And Science In Sports And Exercise, 2024-04-01 00:00:00.0; 56(4), p. 590-599.
EPub date: 2023-11-27 00:00:00.0.
PMID: 38485730
Related Citations

Effects of Exercise Therapy Dosing Schedule on Impaired Cardiorespiratory Fitness in Patients With Primary Breast Cancer: A Randomized Controlled Trial.
Authors: Scott J.M. , Thomas S.M. , Peppercorn J.M. , Herndon J.E. , Douglas P.S. , Khouri M.G. , Dang C.T. , Yu A.F. , Catalina D. , Ciolino C. , et al. .
Source: Circulation, 2020-02-18 00:00:00.0; 141(7), p. 560-570.
EPub date: 2020-02-17 00:00:00.0.
PMID: 32065769
Related Citations

Exercise as a Candidate Antitumor Strategy: A Window into the Future.
Authors: Koelwyn G.J. , Jones L.W. .
Source: Clinical Cancer Research : An Official Journal Of The American Association For Cancer Research, 2019-09-01 00:00:00.0; 25(17), p. 5179-5181.
EPub date: 2019-06-21 00:00:00.0.
PMID: 31227498
Related Citations

Exploration Of Exercise Outcome Expectations Among Breast Cancer Survivors
Authors: Hirschey R. , Docherty S.L. , Pan W. , Lipkus I. .
Source: Cancer Nursing, 2016-02-26 00:00:00.0; , .
PMID: 26925999
Related Citations

Precision Oncology Framework for Investigation of Exercise As Treatment for Cancer.
Authors: Jones L.W. .
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2015-12-10 00:00:00.0; 33(35), p. 4134-7.
EPub date: 2015-12-10 00:00:00.0.
PMID: 26460301
Related Citations

Physical Activity and Prostate Tumor Vessel Morphology: Data from the Health Professionals Follow-up Study.
Authors: Van Blarigan E.L. , Gerstenberger J.P. , Kenfield S.A. , Giovannucci E.L. , Stampfer M.J. , Jones L.W. , Clinton S.K. , Chan J.M. , Mucci L.A. .
Source: Cancer Prevention Research (philadelphia, Pa.), 2015 Oct; 8(10), p. 962-7.
PMID: 26276753
Related Citations

Safety and efficacy of aerobic training in patients with cancer who have heart failure: an analysis of the HF-ACTION randomized trial.
Authors: Jones L.W. , Douglas P.S. , Khouri M.G. , Mackey J.R. , Wojdyla D. , Kraus W.E. , Whellan D.J. , O'Connor C.M. .
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2014-08-10 00:00:00.0; 32(23), p. 2496-502.
EPub date: 2014-08-10 00:00:00.0.
PMID: 25002717
Related Citations

Cancer Therapy-induced Autonomic Dysfunction In Early Breast Cancer: Implications For Aerobic Exercise Training
Authors: Scott J.M. , Jones L.W. , Hornsby W.E. , Koelwyn G.J. , Khouri M.G. , Joy A.A. , Douglas P.S. , Lakoski S.G. .
Source: International Journal Of Cardiology, 2014-02-01 00:00:00.0; 171(2), p. e50-1.
PMID: 24365613
Related Citations

Safety and efficacy of aerobic training in operable breast cancer patients receiving neoadjuvant chemotherapy: a phase II randomized trial.
Authors: Hornsby W.E. , Douglas P.S. , West M.J. , Kenjale A.A. , Lane A.R. , Schwitzer E.R. , Ray K.A. , Herndon J.E. , Coan A. , Gutierrez A. , et al. .
Source: Acta Oncologica (stockholm, Sweden), 2014 Jan; 53(1), p. 65-74.
PMID: 23957716
Related Citations

Immunological and hormonal effects of exercise: implications for cancer cachexia.
Authors: Maddocks M. , Jones L.W. , Wilcock A. .
Source: Current Opinion In Supportive And Palliative Care, 2013 Dec; 7(4), p. 376-82.
PMID: 24157716
Related Citations

Energy Balance And Metabolism After Cancer Treatment
Authors: Tonorezos E.S. , Jones L.W. .
Source: Seminars In Oncology, 2013 Dec; 40(6), p. 745-56.
PMID: 24331194
Related Citations

Efficacy Of Multimodal Exercise-based Rehabilitation On Physical Activity, Cardiorespiratory Fitness, And Patient-reported Outcomes In Cancer Survivors: A Randomized, Controlled Trial
Authors: Midtgaard J. , Christensen J.F. , Tolver A. , Jones L.W. , Uth J. , Rasmussen B. , Tang L. , Adamsen L. , Rørth M. .
Source: Annals Of Oncology : Official Journal Of The European Society For Medical Oncology / Esmo, 2013 Sep; 24(9), p. 2267-73.
PMID: 23704198
Related Citations

Both aerobic exercise and resveratrol supplementation attenuate doxorubicin-induced cardiac injury in mice.
Authors: Dolinsky V.W. , Rogan K.J. , Sung M.M. , Zordoky B.N. , Haykowsky M.J. , Young M.E. , Jones L.W. , Dyck J.R. .
Source: American Journal Of Physiology. Endocrinology And Metabolism, 2013-07-15 00:00:00.0; 305(2), p. E243-53.
EPub date: 2013-07-15 00:00:00.0.
PMID: 23695218
Related Citations

The influence of adjuvant therapy on cardiorespiratory fitness in early-stage breast cancer seven years after diagnosis: the Cooper Center Longitudinal Study.
Authors: Lakoski S.G. , Barlow C.E. , Koelwyn G.J. , Hornsby W.E. , Hernandez J. , Defina L.F. , Radford N.B. , Thomas S.M. , Herndon J.E. , Peppercorn J. , et al. .
Source: Breast Cancer Research And Treatment, 2013 Apr; 138(3), p. 909-16.
PMID: 23504137
Related Citations

Exercise Therapy As Treatment For Cardiovascular And Oncologic Disease After A Diagnosis Of Early-stage Cancer
Authors: Scott J.M. , Koelwyn G.J. , Hornsby W.E. , Khouri M. , Peppercorn J. , Douglas P.S. , Jones L.W. .
Source: Seminars In Oncology, 2013 Apr; 40(2), p. 218-28.
PMID: 23540747
Related Citations

Effects And Potential Mechanisms Of Exercise Training On Cancer Progression: A Translational Perspective
Authors: Betof A.S. , Dewhirst M.W. , Jones L.W. .
Source: Brain, Behavior, And Immunity, 2013 Mar; 30 Suppl, p. S75-87.
PMID: 22610066
Related Citations

Exercise-oncology research: past, present, and future.
Authors: Jones L.W. , Alfano C.M. .
Source: Acta Oncologica (stockholm, Sweden), 2013 Feb; 52(2), p. 195-215.
PMID: 23244677
Related Citations

The potential role of aerobic exercise to modulate cardiotoxicity of molecularly targeted cancer therapeutics.
Authors: Scott J.M. , Lakoski S. , Mackey J.R. , Douglas P.S. , Haykowsky M.J. , Jones L.W. .
Source: The Oncologist, 2013; 18(2), p. 221-31.
PMID: 23335619
Related Citations

Running on empty: cardiovascular reserve capacity and late effects of therapy in cancer survivorship.
Authors: Koelwyn G.J. , Khouri M. , Mackey J.R. , Douglas P.S. , Jones L.W. .
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2012-12-20 00:00:00.0; 30(36), p. 4458-61.
EPub date: 2012-12-20 00:00:00.0.
PMID: 23045598
Related Citations

Cancer Therapy-induced Cardiac Toxicity In Early Breast Cancer: Addressing The Unresolved Issues
Authors: Khouri M.G. , Douglas P.S. , Mackey J.R. , Martin M. , Scott J.M. , Scherrer-Crosbie M. , Jones L.W. .
Source: Circulation, 2012-12-04 00:00:00.0; 126(23), p. 2749-63.
PMID: 23212997
Related Citations

Cardiopulmonary Function And Age-related Decline Across The Breast Cancer Survivorship Continuum
Authors: Jones L.W. , Courneya K.S. , Mackey J.R. , Muss H.B. , Pituskin E.N. , Scott J.M. , Hornsby W.E. , Coan A.D. , Herndon J.E. , Douglas P.S. , et al. .
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2012-07-10 00:00:00.0; 30(20), p. 2530-7.
PMID: 22614980
Related Citations

Exercise Modulation Of The Host-tumor Interaction In An Orthotopic Model Of Murine Prostate Cancer
Authors: Jones L.W. , Antonelli J. , Masko E.M. , Broadwater G. , Lascola C.D. , Fels D. , Dewhirst M.W. , Dyck J.R. , Nagendran J. , Flores C.T. , et al. .
Source: Journal Of Applied Physiology (bethesda, Md. : 1985), 2012 Jul; 113(2), p. 263-72.
PMID: 22604887
Related Citations

Exercise Therapy In The Management Of Dyspnea In Patients With Cancer
Authors: Koelwyn G.J. , Jones L.W. , Hornsby W. , Eves N.D. .
Source: Current Opinion In Supportive And Palliative Care, 2012 Jun; 6(2), p. 129-37.
PMID: 22516976
Related Citations

Prognostic Significance Of Functional Capacity And Exercise Behavior In Patients With Metastatic Non-small Cell Lung Cancer
Authors: Jones L.W. , Hornsby W.E. , Goetzinger A. , Forbes L.M. , Sherrard E.L. , Quist M. , Lane A.T. , West M. , Eves N.D. , Gradison M. , et al. .
Source: Lung Cancer (amsterdam, Netherlands), 2012 May; 76(2), p. 248-52.
PMID: 22112290
Related Citations

Exercise Rehabilitation In Patients With Cancer
Authors: Lakoski S.G. , Eves N.D. , Douglas P.S. , Jones L.W. .
Source: Nature Reviews. Clinical Oncology, 2012 May; 9(5), p. 288-96.
PMID: 22392097
Related Citations

Modulation Of Anthracycline-induced Cardiotoxicity By Aerobic Exercise In Breast Cancer: Current Evidence And Underlying Mechanisms
Authors: Scott J.M. , Khakoo A. , Mackey J.R. , Haykowsky M.J. , Douglas P.S. , Jones L.W. .
Source: Circulation, 2011-08-02 00:00:00.0; 124(5), p. 642-50.
PMID: 21810673
Related Citations

Exercise Behavior, Functional Capacity, And Survival In Adults With Malignant Recurrent Glioma
Authors: Ruden E. , Reardon D.A. , Coan A.D. , Herndon J.E. , Hornsby W.E. , West M. , Fels D.R. , Desjardins A. , Vredenburgh J.J. , Waner E. , et al. .
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2011-07-20 00:00:00.0; 29(21), p. 2918-23.
PMID: 21690470
Related Citations

Effects Of Aerobic Training On Oxidative Status In Postsurgical Non-small Cell Lung Cancer Patients: A Pilot Study
Authors: Jones L.W. , Eves N.D. , Spasojevic I. , Wang F. , Il'yasova D. .
Source: Lung Cancer (amsterdam, Netherlands), 2011 Apr; 72(1), p. 45-51.
PMID: 20863590
Related Citations

Effect Of Exercise Training On Peak Oxygen Consumption In Patients With Cancer: A Meta-analysis
Authors: Jones L.W. , Liang Y. , Pituskin E.N. , Battaglini C.L. , Scott J.M. , Hornsby W.E. , Haykowsky M. .
Source: The Oncologist, 2011; 16(1), p. 112-20.
PMID: 21212429
Related Citations

Association between body mass index and mortality in patients with glioblastoma mutliforme.
Authors: Jones L.W. , Ali-Osman F. , Lipp E. , Marcello J.E. , McCarthy B. , McCoy L. , Rice T. , Wrensch M. , Il'yasova D. .
Source: Cancer Causes & Control : Ccc, 2010 Dec; 21(12), p. 2195-201.
PMID: 20838873
Related Citations

Erratum To: Exercise Therapy In The Management Of Solid Tumors
Authors: Jones L.W. , Peppercorn J. , Scott J.M. , Battaglini C. .
Source: Current Treatment Options In Oncology, 2010 Dec; 11(3-4), p. 73-86.
PMID: 21107922
Related Citations

Pre-exercise Screening And Prescription Guidelines For Cancer Patients
Authors: Jones L.W. , Eves N.D. , Peppercorn J. .
Source: The Lancet. Oncology, 2010 Oct; 11(10), p. 914-6.
PMID: 20708967
Related Citations

Exercise Therapy In The Management Of Solid Tumors
Authors: Jones L.W. , Peppercom J. , Scott J.M. , Battaglini C. .
Source: Current Treatment Options In Oncology, 2010 Jun; 11(1-2), p. 45-58.
PMID: 20645033
Related Citations

Rationale And Design Of The Exercise Intensity Trial (excite): A Randomized Trial Comparing The Effects Of Moderate Versus Moderate To High-intensity Aerobic Training In Women With Operable Breast Cancer
Authors: Jones L.W. , Douglas P.S. , Eves N.D. , Marcom P.K. , Kraus W.E. , Herndon J.E. , Inman B.A. , Allen J.D. , Peppercorn J. .
Source: Bmc Cancer, 2010; 10, p. 531.
PMID: 20925920
Related Citations