Cardiac Outcomes With Near-Complete Estrogen Deprivation

NCT05309655 | Recruiting DMC

• 3 other identifiers: Pro00110774WFBCCC 98122R01HL159393
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this research study is to understand what effect near complete estrogen deprivation (NCED) therapy has on the heart in breast cancer patients. Investigators want to understand if NCED changes how the heart works.

Conditions

Breast Cancer; Triple Negative Breast Cancer; Cardiovascular Complications

Outcome Measures

Primary Outcomes (1)

• Change in Myocardial Blood Flow - 24 months

  Change in myocardial blood flow will be measured by adenosine CMR imaging. Comparisons will be made using longitudinal mixed models to examine within- and between- group effects on outcomes measured. These mixed models will include fixed effects for group (NCED/TNBC), baseline assessment of the outcome of interest (i.e. MPR) to adjust for potential risk-factor profile differences between groups and the time point at which the measurements are made relative to the baseline assessment.

  At baseline and at 24 months

Secondary Outcomes (6)

• Change in Myocardial Blood Flow - 12 months

  At baseline and at 12 months

• Change in Stiffness - Thoracic Pulse Wave Velocity

  At 12 months and at 24 months

• Change in Myocardial Perfusion Reserves

  At 12 months and at 24 months

• Number of Women at High Risk for Developing Deficits in Myocardial Blood Flow

  At 24 months

• Overall Survival

  Up to 5 years

Study Arms (1)

Near-Complete Estrogen Deprivation Therapy Participants

EXPERIMENTAL

Participants will receive cardiac imaging stress tests as well as study laboratory tests to monitor for changes in heart as well 30-day at the end of the study along with annual long-term follow up to 5 years from baseline imaging.

Drug: Adenosine Stress Cardiac Magnetic Resonance Imaging; Diagnostic Test: Electrocardiogram; Diagnostic Test: Computed Tomography Angiogram; Other: Laboratory Testing; Behavioral: Quality of Life Survey

Interventions

Adenosine Stress Cardiac Magnetic Resonance Imaging DRUG

Adenosine stress CMR test with contrast to include cardiovascular structural and functional measures including myocardial blood flow through quantitative perfusion mapping. Participants will have 3 stress tests as a part of this research. These tests will happen when at the beginning of the study, and then every year for 2 years.

Near-Complete Estrogen Deprivation Therapy Participants

Electrocardiogram DIAGNOSTIC_TEST

A 12-lead electrocardiogram will be done when at the start of the study and at the participant's 2 year stress test to look at the electrical signals of your heart.

Near-Complete Estrogen Deprivation Therapy Participants

Computed Tomography Angiogram DIAGNOSTIC_TEST

Contrasted coronary CT angiography will be performed for visual and quantitative analysis of coronary artery plaque burdens.

Near-Complete Estrogen Deprivation Therapy Participants

Laboratory Testing OTHER

10 teaspoons of blood will be withdrawn at every visit that participants receive a stress test. Participants may have up to six blood draws associated with each imaging visit.

Near-Complete Estrogen Deprivation Therapy Participants

Quality of Life Survey BEHAVIORAL

A general health status survey with 10 questions and should take about 5-10 minutes to finish. This survey is related to research.

Near-Complete Estrogen Deprivation Therapy Participants

Eligibility Criteria

• Age: 18 Years - 55 Years
• Gender Eligibility Details: Premenopausal women that are receiving or have received therapy for breast cancer.
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Duke University: lead
• National Cancer Institute (NCI): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (3)

Duke Cancer Center

Durham, North Carolina, 27710, United States

RECRUITING

Wake Forest Baptist Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157, United States

RECRUITING

Virginia Commonwealth University Massey Cancer Center

Richmond, Virginia, 23298, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

Electrocardiography

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Electrodiagnosis

Study Officials

• Alexandra Thomas, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sarah Hatcher, MPH

CONTACT

9196840591; sarah.hatcher@duke.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Investigators will recruit 90 women, 67 who will be in the near-complete estrogen deprivation (NCED) group and 23 in the triple-negative breast cancer (TNBC) group. This will allow for approximately a 10% loss-to-follow-up rate and will allow investigators to have 60 participants in the NCED group and 20 in the TNBC with 2-year of data. There are 2 primary types of statistical analyses to address the study questions. The first includes testing hypotheses concerning between group (NCED vs TNBC) and within group (i.e. longitudinal changes within the NCED group) comparisons (Aims 1 and 2). The second analyses involve developing predictive equations among the NCED patients to determine if patient demographics including age, race, ethnicity, social determinants of health, clinical parameters, serum biomarkers and/or markers of inflammation are associated with cardiovascular changes over time.

Study Record Dates

• First Submitted: March 25, 2022
• First Posted: April 4, 2022
• Study Start: September 2, 2022
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: March 16, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)