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.