Abstract PO3-19-04: The CROWN STUDY: A multicenter prospective cohort study of cardiovascular outcomes in premenopausal women with hormone receptor positive breast cancer treated with ovarian suppression and an aromatase inhibitor
Authors: Dent Susan , Douglas Emily , Hatcher Sarah , Ansley Katherine , Park Carolyn , O'Connell Nathaniel , Hackney Mary , D'Agostino Ralph , Bansal Rani , Avecilla Renee , Brown Monica , Clayton-Stiglbauer Kacey , Klem Igor , Jordan Jennifer , Thomas Alexandra 
Published: May 2024

Background: Treatment for premenopausal women with high or intermediate risk hormone receptor (HR)+ breast cancer (BC) includes the concurrent use of ovarian function suppression (OFS) and an aromatase inhibitor (AI) to induce near complete estrogen deprivation (NCED). The long-term cardiovascular (CV) sequela for women treated with NCED is unknown. Premature menopause in non-cancer populations is associated with CV disease. The CROWN study (CaRdiac Outcomes With Near complete estrogen deprivation) will use sophisticated imaging assessments of cardiac dysfunction to understand the evolution of CV injury, as well as biomarker and demographic correlates, with the goal of developing tools to assess and mitigate CV risk.

Methods: This is a NIH funded prospective cohort study conducted at 3 regional NCI-supported Cancer Centers (Atrium Health Wake Forest Baptist, Virginia Commonwealth and Duke) that will include premenopausal women, age ≤ 55, with Stage I-III BC following completion of planned chemotherapy, surgery and radiation with an ECOG 0-1. HR+ BC patients will receive an AI and OFS. Women with HR- BC are included as comparators. CV imaging and biomarkers will be obtained at baseline, 1 year and 2 years (Table 1). These assessments will include serial cardiac magnetic resonance (CMR) and coronary computed tomography angiography (CCTA) imaging as well as laboratory measurements, including exploratory biomarkers. The primary objective is to determine the 24-month difference in stress myocardial blood flow as measured by adenosine CMR imaging in both groups. We will correlate CMR imaging with CCTA to provide complementary detail of coronary plaque changes. The study will also assess the relevance of pre-existing risk factors on study outcomes, including an emphasis on racial disparities, and dynamic change in modifiable and treatment related risk factors.

We plan to enroll 90 women, 67 in the NCED group and 23 in the HR-group, allowing for a 10% drop out rate. There are two primary types of statistical analyses. The first includes testing hypotheses between group (NCED vs HR-) and within group (longitudinal changes within the NCED group). The second analyses, involve developing predictive equations utilizing a stepwise linear regression approach to determine if patient demographics, clinical parameters and serum biomarkers are associated with cardiovascular changes over time. A total of 17 patients are enrolled as of 07/2023. NCT05309655

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Citation Format: Susan Dent, Emily Douglas, Sarah Hatcher, Katherine Ansley, Carolyn Park, Nathaniel O'Connell, Mary Hackney, Ralph D'Agostino, Rani Bansal, Renee Avecilla, Monica Brown, Kacey Clayton-Stiglbauer, Igor Klem, Jennifer Jordan, Alexandra Thomas. The CROWN STUDY: A multicenter prospective cohort study of cardiovascular outcomes in premenopausal women with hormone receptor positive breast cancer treated with ovarian suppression and an aromatase inhibitor [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-19-04.