Hormone Therapy for Cardiovascular Health in Breast Cancer Patients

(CROWN Trial)

Recruiting at 2 trial locations

Overseen By Sarah Hatcher, MPH

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: Duke University

Must be taking: Aromatase inhibitors, SERD

Disqualifiers: Pregnancy, Cardiac arrhythmia, Uncontrolled illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how near-complete estrogen deprivation (NCED) therapy affects the heart in breast cancer patients. Researchers will monitor heart function using imaging and lab tests to determine if this hormone therapy alters heart function over time. Women diagnosed with Stage I-III breast cancer and planning to undergo NCED therapy might be suitable candidates for this study.

As an unphased trial, this study offers patients a unique opportunity to contribute to important research that could enhance future breast cancer treatments.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it allows certain treatments like CDK-inhibitors, PARP inhibitors, and SERDs, so you might be able to continue some medications. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that near-complete estrogen deprivation therapy is likely to be safe for humans?

Research has shown that near-complete estrogen deprivation (NCED) therapy might pose risks to heart health. Studies have found that women who suddenly lose estrogen, particularly those with breast cancer, may face a higher risk of heart problems. These issues can include heart disease or even heart failure over time. While NCED helps reduce the chance of breast cancer recurrence, awareness of these potential heart-related side effects is crucial. Discuss any concerns with a healthcare provider to understand the benefits and risks. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for cardiovascular health in breast cancer patients, which typically include medications like beta-blockers and ACE inhibitors, Near-Complete Estrogen Deprivation Therapy offers a novel approach. Researchers are excited about this treatment because it targets estrogen levels, which can be pivotal in managing heart health for breast cancer patients. This therapy involves monitoring patients through cardiac imaging stress tests and laboratory tests to observe heart changes, providing a comprehensive understanding of how reducing estrogen impacts cardiovascular health. This innovative focus on estrogen deprivation could lead to more personalized and effective care for patients balancing cancer treatment and heart health.

What evidence suggests that near-complete estrogen deprivation therapy might be an effective treatment for cardiovascular health in breast cancer patients?

Research shows that treatments causing almost complete loss of estrogen can affect heart health, especially in breast cancer patients. Studies indicate that women who suddenly lose estrogen may face a higher risk of heart problems, such as heart disease and heart failure. Previous research in women without cancer found that sudden menopause can lead to more heart issues. This trial will study Near-Complete Estrogen Deprivation Therapy to monitor its effects on heart health in breast cancer patients. However, the long-term impact of these treatments on heart health remains unclear, and more research is needed to understand these possible risks. ^{1 2 3 4 6}

Who Is on the Research Team?

Alexandra Thomas, MD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

This trial is for women ≤55 years old, premenopausal at breast cancer diagnosis, with Stage I-III HER2 negative or positive breast cancer. They must be starting NCED therapy soon and have an ECOG performance status of 0-2. Patients on certain other non-chemotherapy treatments are eligible. Exclusions include men, those with renal insufficiency, severe heart conditions, metal implants incompatible with MRI, pregnancy, asthma/COPD requiring medication, or allergies to study substances.

Inclusion Criteria

I am starting or have started breast cancer treatment with hormone therapy after menopause induction.

Ability to understand and the willingness to sign an IRB-approved informed consent document

I am being treated with SERD instead of an aromatase inhibitor.

Exclusion Criteria

You are allergic to gadolinium or other contrast agents.

I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

I am experiencing heart symptoms that need urgent investigation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive near complete estrogen deprivation therapy and undergo cardiac imaging stress tests

24 months

Regular visits for imaging and laboratory tests

Follow-up

Participants are monitored for safety and effectiveness after treatment, including annual long-term follow-up

Up to 5 years

Annual visits

What Are the Treatments Tested in This Trial?

Interventions

• Near-Complete Estrogen Deprivation Therapy

Trial Overview The study aims to assess the impact of near-complete estrogen deprivation (NCED) therapy on heart function in breast cancer patients using various diagnostic tools like electrocardiograms (ECGs), stress cardiac MRIs, CT angiograms and lab tests alongside quality of life surveys.

How Is the Trial Designed?

Group I: Near-Complete Estrogen Deprivation Therapy Participants Experimental Treatment 5 Interventions

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.

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The CROWN study is investigating the cardiovascular effects of near-complete estrogen deprivation therapy in 90 premenopausal women with breast cancer, focusing on early signs of cardiovascular disease using advanced imaging techniques over a two-year period.

Understanding the cardiovascular risks associated with aromatase inhibition and ovarian function suppression is crucial for developing strategies to prevent heart-related complications in young women undergoing breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular impact of near complete estrogen deprivation in premenopausal women with breast cancer: The CROWN study. Thomas, A., O'Connell, NS., Douglas, E., et al.[2023]

Tamoxifen may provide short-term heart protection for women undergoing treatment for breast cancer, but its long-term cardiovascular effects are less favorable.

The impact of aromatase inhibitors (AIs) on heart health is still debated, and more research is needed to understand the cardiovascular risks associated with gonadotrophin-releasing hormone agonists (GNRHa), especially since they may increase cardiac event risks in men.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Cardiovascular Risks Associated with Aromatase Inhibitors, Tamoxifen, and GnRH Agonists in Women with Breast Cancer. Alfaris, I., Asselah, J., Aziz, H., et al.[2023]

In a study of 34,946 women with breast cancer, those treated with aromatase inhibitors (AIs) showed a 20% increased risk of heart failure and a 14% increased risk of any cardiovascular event compared to those treated with tamoxifen over a median follow-up of 5.8 years.

The risk of cardiovascular events was notably higher in women with pre-existing conditions such as hypertension, diabetes, and dyslipidemia, indicating that AIs may pose additional risks for patients with these factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant Hormonotherapy and Cardiovascular Risk in Post-Menopausal Women with Breast Cancer: A Large Population-Based Cohort Study. Franchi, M., Tritto, R., Tarantini, L., et al.[2021]

In a study of 16,289 women with early-stage estrogen receptor-positive breast cancer, tamoxifen treatment showed no significant association with the occurrence of serious cardiovascular events like angina, heart attack, heart failure, or stroke during the first five years of therapy.

The findings suggest that tamoxifen does not increase the risk of atherosclerotic events, which is important for evaluating the overall benefits and risks of tamoxifen compared to newer treatments like aromatase inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tamoxifen treatment in Danish breast cancer patients and 5-year risk of arterial atherosclerotic events: a null association. Hernandez, RK., Sørensen, HT., Jacobsen, J., et al.[2022]

Tamoxifen users showed an increased risk of venous thromboembolism compared to non-users and those using aromatase inhibitors, indicating a potential safety concern with this treatment.

Aromatase inhibitor users had a higher risk of myocardial infarction and angina compared to tamoxifen users, suggesting that tamoxifen may offer some protective effects against these cardiovascular issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long term adjuvant endocrine therapy and risk of cardiovascular disease in female breast cancer survivors: systematic review. Matthews, A., Stanway, S., Farmer, RE., et al.[2022]

In a study of 19 postmenopausal women with advanced ER+/HER2- breast cancer, alternating treatment with 17β-estradiol and aromatase inhibitors showed a clinical benefit rate of 42.1%, indicating potential effectiveness for patients who have not responded to previous therapies.

The presence of ESR1 mutations in tumors was associated with better clinical outcomes, as 57.1% of patients with these mutations experienced clinical benefit from the treatment, suggesting that genetic profiling may help tailor therapy for improved results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alternating 17β-Estradiol and Aromatase Inhibitor Therapies Is Efficacious in Postmenopausal Women with Advanced Endocrine-Resistant ER+ Breast Cancer. Schwartz, GN., Kaufman, PA., Giridhar, KV., et al.[2023]

Hormone therapy for breast cancer, particularly anti-estrogen treatments, is essential for managing estrogen receptor-positive cases but can negatively impact cardiovascular health over time.

The review suggests a personalized management approach for women undergoing hormone therapy, incorporating cardiovascular risk assessments and potentially using new antidiabetic medications to address metabolic syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hormone therapy, cardio-metabolic profile and cardiotoxicity. Still a dark side of cardio-oncology. Part 1: Breast cancer]. Tarantini, L., Foglietta, J., Gori, S., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37890547/

Cardiovascular impact of near complete estrogen deprivation ... The CaRdiac Outcomes With Near-complete estrogen deprivation (CROWN) study seeks to understand the early, subclinical natural history of cardiovascular ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS12146

The CROWN study: Cardiac outcomes with near-complete ... The long-term cardiovascular (CV) sequela for women treated with NCED is unknown. Premature menopause in non-cancer populations is associated ...

3. dukecancerinstitute.org dukecancerinstitute.org/center/center-onco-primary-care/cardiac-outcomes-near-complete-estrogen-deprivation-crown-study

The Cardiac Outcomes with Near-complete Estrogen ... The long-term effect of estrogen depletion in young breast cancer survivors puts them at increased risk of heart disease, including heart failure and heart ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT405732

The CROWN study (CaRdiac Outcomes With Near ... The long-term cardiovascular (CV) sequela for women treated with NCED is unknown. Premature menopause in non-cancer populations is associated with CV disease.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10976295/

Cardiovascular Impact of Near Complete Estrogen ... Abrupt estrogen deprivation for non-cancer reasons is associated with accelerated coronary artery disease. Women with breast cancer treated with ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0002870323003009

Cardiovascular impact of near complete estrogen ... The CROWN study seeks to understand the natural history of women embarking on NCED to lower the risk of breast cancer recurrence.