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Cardiovascular impact of near complete estrogen deprivation in premenopausal women with breast cancer: The CROWN study - 07/12/23

Doi : 10.1016/j.ahj.2023.10.007 
Alexandra Thomas, MD a, b, Nathaniel S. O'Connell, PhD b, Emily Douglas, MD a, b, Sarah Hatcher, MPH a, b, Carolyn J. Park, MD a, Susan Dent, MD c, Katherine Ansley, MD a, b, Igor Klem, MD d, Rani Bansal, MD c, Kelly Westbrook, MD c, W. Gregory Hundley, MD e, Wendy Bottinor, MD e, Mary Helen Hackney, MD f, Karl M. Richardson, MD a, Sherona R. Sirkisoon, PhD b, Ralph B. D'Agostino, PhD b, Jennifer H. Jordan, PhD e, g,
a Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 
b Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC 
c Duke Cancer Institute, Department of Medicine, Duke University, Durham, NC 
d Duke Cardiovascular Magnetic Resonance Center, Duke University Medical Center, Durham, NC 
e Division of Cardiology, Pauley Heart Center, Virginia Commonwealth University, Richmond, VA 
f Division of Hematology, Oncology and Palliative Care, Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA 
g Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 

Reprint requests: Jennifer H. Jordan PhD, MS, FSCMR, Suite 8-119, West Hospital, 1200 E. Broad Street, Richmond, VA 23298.Suite 8-119, West Hospital, 1200 E. Broad StreetRichmondVA23298

Riassunto

Survival with operable breast cancer has improved markedly in recent decades, however, treatment-related cardiovascular toxicities threaten to offset these gains. Ovarian function suppression paired with aromatase inhibition, for premenopausal women with hormone receptor (HR)-positive breast cancer, is a newer widely adopted therapy with the potential for significant long-term cardiovascular toxicity. Abrupt estrogen deprivation for non-cancer reasons is associated with accelerated coronary artery disease. Women with breast cancer treated with aromatase inhibition in addition to ovarian function suppression experience a dual hit with regards to estrogen exposure. The CaRdiac Outcomes With Near-complete estrogen deprivation (CROWN) study seeks to understand the early, subclinical natural history of cardiovascular compromise in young women undergoing near-complete estrogen deprivation (NCED) therapy. It is critical to understand the early subclinical development of cardiovascular disease to identify a window for therapeutic intervention before overt cardiovascular events occur. This three-site regional study (Atrium Health Wake Forest, Duke, and Virginia Commonwealth University) uses serial stress cardiac magnetic resonance (CMR) imaging and cardiac computed tomography angiography (CCTA) obtained during the initial two years of NCED therapy to study myocardial prefusion reserve (MPR), large cardiovascular vessel changes, left ventricular function, and other cardiovascular parameters. The CROWN cohort will consist of 90 premenopausal women with breast cancer, 67 with HR-positive disease receiving NCED and 23 comparators with HR-negative disease. Participants will undergo three annual CMR scans and 2 CCTA scans during the 2-year study period. After initial activation hurdles, accrual has been brisk, and the study is expected to complete accrual in December 2024. Efforts are in place to encourage participant retention with the study primary outcome, change in MPR between the two groups, to be reported in 2026 to 2027. The results of this study will enable premenopausal women with breast cancer to balance the health burdens of cancer at a young age and treatment-related cardiovascular morbidity. Finally, the tools developed here can be utilized to study cardiovascular risk across a range of cancer types and cancer therapies with the ultimate goals of both developing generalizable risk stratification tools as well as validating interventions which prevent overt cardiovascular compromise.

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P. 33-43 - Gennaio 2024 Ritorno al numero
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