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Grant Details

Grant Number: 5R01CA199167-06 Interpret this number
Primary Investigator: Hundley, William
Organization: Wake Forest University Health Sciences
Project Title: Understanding and Predicting Fatigue, Cv Decline & Events After Breast CA Treatment
Fiscal Year: 2022


 DESCRIPTION (provided by applicant): Though the use of chemotherapy and early detection methods have greatly increased survival rates for women with Stage I-III breast cancer, this progress is threatened by a significant increase in cardiovascular (CV) events for survivors. Over 35% of women experience CV injury, left ventricular (LV) dysfunction, exercise intolerance, or fatigue after receipt of adjuvant chemotherapy (Adj-C) for Stage I-III breast cancer. In addition, CV events are the leading cause of morbidity and mortality for those surviving 5 to 8 years after their breast cancer diagnosis. Currently, little is understood about te origins of CV dysfunction, exercise intolerance, or fatigue in these women, and risk prediction algorithms for CV events do not incorporate breast cancer treatment in their models. We propose a study of baseline and serial longitudinal measures that will determine the influence of Adj-C with and without concomitant radiation treatment on 3 general categories: (1) CV function, (2) exercise capacity and fatigue, and (3) future development of CV events in a cohort of 1,000 women (840 with Stage I-III Breast Cancer and 160 healthy comparators). We also seek to answer questions about the relationship of alterations in LV and aortic function, what demographic risk factors and changes in serum biomarkers precede LV dysfunction, and if risk factor prediction models forecast development of CV events in the same cohort. Our longitudinal study design accounts for pre-existing and dynamic changes in risk factors during receipt of Adj-C and assesses subsequent CV events. This study has secured robust financial and infrastructure support through the Wake Forest NCI Community Oncology Research Program. This partnership reduces the overall cost of the current proposal by funding enrollment, staff reimbursement, regulatory oversight, study database development, echocardiograms, and an active surveillance program to ascertain the occurrence of CV events. This will be the first epidemiologic cohort study designed to fully characterize the time course and define the correlates of subclinical CV dysfunction, exercise intolerance, fatigue and CV events in women treated with Adj-C for breast cancer. A study of this magnitude is important to assess a variety of subjects so that the scientific community may better understand who is at risk and how we can prevent future CV damage. By enrolling patients in community hospitals and utilizing the unique expertise of each Co-Investigator, this study can capture the data needed to make such predictions. The immediate impact of this research will reduce the gaps in knowledge that prevent treatment design and generate risk prediction algorithms to avert CV events in breast cancer survivors. New knowledge from this study will quantify the risk of developing subclinical CV disease and exercise intolerance in this population, identify potential mechanisms, and inform future study development to reduce CV disease and improve overall survival in women with breast cancer.


Statins for Cardiac and Vascular Protection During and After Cancer Therapy.
Authors: Heiston E.M. , Hundley W.G. .
Source: Current oncology reports, 2022 May; 24(5), p. 555-561.
EPub date: 2022-02-24.
PMID: 35199294
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Automated Noncontrast Myocardial Tissue Characterization for Hypertrophic Cardiomyopathy: Holy Grail or False Prophet?
Authors: Manisty C.H. , Jordan J.H. , Hundley W.G. .
Source: Circulation, 2021-08-24; 144(8), p. 600-603.
EPub date: 2021-08-23.
PMID: 34424773
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Both intermuscular fat and LVEF decline promote heart failure symptoms in cancer survivors.
Authors: Reding K.W. , O'Connell N.S. , D'Agostino R.B. , Hundley W. , Lucas A.R. , Ladd A.C. , Jordan J.H. , Heiston E.M. , Ge Y. , Hundley W.G. .
Source: Cardio-oncology (London, England), 2021-05-08; 7(1), p. 16.
EPub date: 2021-05-08.
PMID: 33964981
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The relationship between abdominal fat and change in left ventricular ejection fraction in cancer patients.
Authors: Reding K.W. , Ghemigian K. , Carbone S. , D'Agostino R. , Jordan J.H. , Meléndez G. , Lamar Z.S. , Klepin H.D. , Thomas A. , Langford D. , et al. .
Source: Obesity science & practice, 2021 Feb; 7(1), p. 82-90.
EPub date: 2020-10-16.
PMID: 33680495
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The Role of Cardiovascular MRI in Cardio-Oncology.
Authors: Bottinor W. , Trankle C.R. , Hundley W.G. .
Source: Heart failure clinics, 2021 Jan; 17(1), p. 121-133.
EPub date: 2020-10-28.
PMID: 33220881
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Mid-Cancer Left Ventricular Function Measures Predict Long-Term Post-Cancer Left Ventricular Ejection Fraction.
Authors: Hundley W.G. , D'Agostino R.B. .
Source: JACC. Cardiovascular imaging, 2020 Dec; 13(12), p. 2697.
EPub date: 2020-08-26.
PMID: 32861650
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Effect at One Year of Adjuvant Trastuzumab for HER2+ Breast Cancer Combined with Radiation or an Anthracycline on Left Ventricular Ejection Fraction.
Authors: Andersen M.M. , Ayala-Peacock D. , Bowers J. , Kooken B.W. , D'Agostino R.B. , Jordan J.H. , Vasu S. , Thomas A. , Klepin H.D. , Brown D.R. , et al. .
Source: The American journal of cardiology, 2020-06-15; 125(12), p. 1906-1912.
EPub date: 2020-04-02.
PMID: 32331711
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MRI of Cardiotoxicity.
Authors: Jordan J.H. , Hundley W.G. .
Source: Cardiology clinics, 2019 Nov; 37(4), p. 429-439.
EPub date: 2019-08-31.
PMID: 31587784
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Exercise Capacity Is Reduced in Cancer Survivors Previously Treated With Anthracycline-Based Chemotherapy Despite a Preserved Cardiac Output Response.
Authors: Brubaker P. , Jensen A. , Jordan J. , Lamar Z. , Mihalko S. , Haykowsky M. , Jones L. , D Agostino R. , Kitzman D. , Reding K. , et al. .
Source: JACC. Cardiovascular imaging, 2019 Nov; 12(11 Pt 1), p. 2267-2269.
EPub date: 2019-07-17.
PMID: 31326490
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The Evolving Design of NIH-Funded Cardio-Oncology Studies to Address Cancer Treatment-Related Cardiovascular Toxicity.
Authors: Minasian L. , Dimond E. , Davis M. , Adhikari B. , Fagerstrom R. , Fabian C. , Floyd J. , Unger J.M. , Douglas P.S. , Mustian K.M. , et al. .
Source: JACC. CardioOncology, 2019 Sep; 1(1), p. 105-113.
EPub date: 2019-09-24.
PMID: 32529192
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Increased skeletal intermuscular fat is associated with reduced exercise capacity in cancer survivors: a cross-sectional study.
Authors: Reding K.W. , Brubaker P. , D'Agostino R. , Kitzman D.W. , Nicklas B. , Langford D. , Grodesky M. , Hundley W.G. .
Source: Cardio-oncology (London, England), 2019; 5, p. 3.
EPub date: 2019-05-03.
PMID: 32154010
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The Role of Cardiovascular Magnetic Resonance for Surveillance of Cardiac Performance upon Receipt of Potentially Cardiotoxic Cancer Therapeutics.
Authors: Parashar A. , Hundley W.G. .
Source: Current cardiology reports, 2018-10-26; 20(12), p. 142.
EPub date: 2018-10-26.
PMID: 30367282
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Accelerated Left Ventricular Interstitial Collagen Deposition After Receiving Doxorubicin in Hypertension.
Authors: Meléndez G.C. , Jordan J.H. , D'Agostino R.B. , Lesnefsky E.J. , Hundley W.G. .
Source: Journal of the American College of Cardiology, 2018-09-25; 72(13), p. 1555-1557.
PMID: 30236317
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Cardiovascular Magnetic Resonance in the Oncology Patient.
Authors: Jordan J.H. , Todd R.M. , Vasu S. , Hundley W.G. .
Source: JACC. Cardiovascular imaging, 2018 Aug; 11(8), p. 1150-1172.
PMID: 30092971
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When Left Ventricular Extracellular Volume Fraction Changes After Anthracyclines: Is it Due to a Change in the Numerator, Denominator, or Both?
Authors: Hundley W.G. , Jordan J.H. .
Source: JACC. Cardiovascular imaging, 2018 Aug; 11(8), p. 1056-1058.
PMID: 30092966
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Left Ventricular Mass Change After Anthracycline Chemotherapy.
Authors: Jordan J.H. , Castellino S.M. , Meléndez G.C. , Klepin H.D. , Ellis L.R. , Lamar Z. , Vasu S. , Kitzman D.W. , Ntim W.O. , Brubaker P.H. , et al. .
Source: Circulation. Heart failure, 2018 Jul; 11(7), p. e004560.
PMID: 29991488
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Early Myocardial Strain Changes During Potentially Cardiotoxic Chemotherapy May Occur as a Result of Reductions in Left Ventricular End-Diastolic Volume: The Need to Interpret Left Ventricular Strain With Volumes.
Authors: Jordan J.H. , Sukpraphrute B. , Meléndez G.C. , Jolly M.P. , D'Agostino R.B. , Hundley W.G. .
Source: Circulation, 2017-06-20; 135(25), p. 2575-2577.
PMID: 28630272
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Progressive 3-Month Increase in LV Myocardial ECV After Anthracycline-Based Chemotherapy.
Authors: Meléndez G.C. , Jordan J.H. , D'Agostino R.B. , Vasu S. , Hamilton C.A. , Hundley W.G. .
Source: JACC. Cardiovascular imaging, 2017 Jun; 10(6), p. 708-709.
EPub date: 2016-08-17.
PMID: 27544895
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Is Myocardial Fibrosis a New Frontier for Discovery in Cardiotoxicity Related to the Administration of Anthracyclines?
Authors: Meléndez G.C. , Hundley W.G. .
Source: Circulation. Cardiovascular imaging, 2016 Dec; 9(12), .
PMID: 27923797
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Anthracycline-Associated T1 Mapping Characteristics Are Elevated Independent of the Presence of Cardiovascular Comorbidities in Cancer Survivors.
Authors: Jordan J.H. , Vasu S. , Morgan T.M. , D'Agostino R.B. , Meléndez G.C. , Hamilton C.A. , Arai A.E. , Liu S. , Liu C.Y. , Lima J.A. , et al. .
Source: Circulation. Cardiovascular imaging, 2016 Aug; 9(8), .
PMID: 27502058
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