Effects of near-complete estrogen deprivation on heart health in breast cancer patients

The Cardiac Outcomes With Near-Complete Estrogen Deprivation (CROWN) Study

This study is testing how near-complete estrogen deprivation therapy affects heart health in premenopausal women with breast cancer compared to those who are not receiving this treatment.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 90 (estimated)
• Ages: 18 Years to 55 Years
• Sex: Female
• Sponsor: Duke University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 3 sites (Durham, North Carolina and 2 other locations)
• Trial ID: NCT05309655 on ClinicalTrials.gov

What this trial studies

This research investigates the impact of near-complete estrogen deprivation (NCED) therapy on cardiac function in premenopausal women diagnosed with breast cancer. The study aims to compare myocardial blood flow and aortic stiffness between women receiving NCED for hormone receptor-positive breast cancer and those not receiving NCED for hormone receptor-negative breast cancer. Using advanced imaging techniques like cardiovascular magnetic resonance imaging (CMR) and computed tomography angiography, the study will assess changes in heart health over a 24-month period. The findings could provide insights into the cardiovascular risks associated with breast cancer treatments.

Who should consider this trial

Good fit: Ideal candidates are premenopausal women aged 55 or younger who are undergoing treatment for breast cancer and are either receiving or not receiving NCED therapy.

Not a fit: Patients who are postmenopausal or those with breast cancer types not specified in the eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could help identify cardiac risks associated with breast cancer treatments, leading to better management strategies for patients.

How similar studies have performed: While the specific approach of this study may be novel, similar studies have indicated potential cardiovascular impacts of breast cancer therapies, suggesting a need for further investigation.

Eligibility criteria

Inclusion Criteria

* Women age ≤55 who were premenopausal at the time of breast cancer diagnosis; (Premenopausal is defined as per NCCN criteria).
* Planned breast cancer treatment with NCED (near-complete estrogen deprivation) therapy that includes aromatase inhibitor therapy (or SERD) with medically or surgically induced menopause within three (3) months of initiating NCED (HR-positive tumor) or, for the cohorts not receiving NCED therapy, within three (3) months of planned chemotherapy, surgery or radiation. Index date for three months is defined as final date of treatment with chemotherapy, surgery or radiation which ever happens last (HR-negative tumor). Treatment with a Gonadotropin Releasing Hormone (GnRH) agonist for fertility preservation during chemotherapy is allowed and is not considered part of the NCED antineoplastic therapy.
* Women with human epidermal growth factor-2 (HER2) negative and women with human epidermal growth factor-2 (HER2) positive breast cancer are eligible.
* Treatment with CDK-inhibitor, PARP inhibitor immunotherapy or biologic (non-chemotherapy) agent as part of anti-neoplastic treatment plan is allowed. These agents are not considered chemotherapy.
* Treatment with selective-estrogen receptor degrader (SERD) rather than aromatase inhibitor is allowed.
* Diagnosed with Stage I-III breast cancer.
* ECOG performance status of 0-2
* Patients with concurrent malignancies are eligible as long as therapies and disease course for these are reasonably expected to not impact cardiovascular function. (Examples of eligible malignancies include: papillary/follicular thyroid cancer, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in-situ and early stage cervical cancers, etc.).
* Patients with prior COVID-19 are eligible if they have recovered from the illness and are free of COVID-related symptoms other than allowable persistent symptoms: loss of taste and smell and/or grade 1 fatigue.
* Ability to understand and the willingness to sign an IRB-approved informed consent document (either directly or via a legally authorized representative).
* The study will allow up to 30% of patients with MRI non-compatible breast expanders recognizing that baseline CMR will be outside of imaging window. Note: Registration of these participants will require study PI approval (Dr. Jordan or Dr. Thomas).

Exclusion Criteria:

* History of allergic reactions attributed to compounds of similar chemical or biologic composition to adenosine
* Active wheezing.
* Those with contraindications for MRI such as ferromagnetic cerebral aneurysm clips or other intracranial metal, pacemakers, defibrillators, functioning neurostimulator devices or other implanted electronic devices, or some breast expanders.
* Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Pregnant women are excluded from this study. Because some methods of birth control are not 100% reliable, a pregnancy test is required, unless the patient has undergone either a bilateral oophorectomy, hysterectomy or both.
* Coronary revascularization in the past 6 months or known severe multi-vessel coronary artery disease previously determined to be not amendable to mechanical intervention.
* Ongoing, unrelieved symptoms thought to represent cardiac ischemia and requiring immediate cardiac catheterization
* Allergy or prior sensitivity to gadolinium or other contrasting agents or their excipients.
* Men with breast cancer.
* Known chronic renal insufficiency or chronic electrolyte abnormalities as determined by the treating physician.

Where this trial is running

Durham, North Carolina and 2 other locations

• Duke Cancer Center — Durham, North Carolina, United States (Recruiting)
• Wake Forest Baptist Comprehensive Cancer Center — Winston-Salem, North Carolina, United States (Recruiting)
• Virginia Commonwealth University Massey Cancer Center — Richmond, Virginia, United States (Recruiting)

Study contacts

• Principal investigator: Alexandra Thomas, MD — Duke University
• Study coordinator: Sarah Hatcher, MPH

Conditions Breast Cancer; Triple Negative Breast Cancer; Cardiovascular Complications