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?

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.

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 hormone therapy for breast cancer safe for cardiovascular health?

Hormone therapies like aromatase inhibitors and ovarian function suppression, used in breast cancer treatment, may pose a risk of cardiovascular issues, such as heart disease, especially in premenopausal women. Studies are ongoing to better understand these risks and to find ways to manage them effectively. ^{1 2 3 4 5}

How is Near-Complete Estrogen Deprivation Therapy different from other treatments for breast cancer?

Near-Complete Estrogen Deprivation Therapy is unique because it combines ovarian function suppression with aromatase inhibition, leading to a significant reduction in estrogen levels. This dual approach is newer and may pose a higher risk of cardiovascular issues compared to other hormone therapies, which is why its cardiovascular effects are being closely studied. ^{1 2 4 5 6}

What data supports the effectiveness of the treatment Near-Complete Estrogen Deprivation Therapy for cardiovascular health in breast cancer patients?

The CROWN study is investigating the cardiovascular effects of Near-Complete Estrogen Deprivation Therapy in premenopausal women with breast cancer, focusing on early signs of heart issues to find ways to prevent them. While the study is ongoing, it aims to help balance cancer treatment benefits with potential heart health risks. ^{1 2 4 5 7}

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]

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]

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]

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]

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]

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. United States pubmed.ncbi.nlm.nih.gov

Cardiovascular impact of near complete estrogen deprivation in premenopausal women with breast cancer: The CROWN study. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Tamoxifen treatment in Danish breast cancer patients and 5-year risk of arterial atherosclerotic events: a null association. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Alternating 17β-Estradiol and Aromatase Inhibitor Therapies Is Efficacious in Postmenopausal Women with Advanced Endocrine-Resistant ER+ Breast Cancer. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Long term adjuvant endocrine therapy and risk of cardiovascular disease in female breast cancer survivors: systematic review. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

The Cardiovascular Risks Associated with Aromatase Inhibitors, Tamoxifen, and GnRH Agonists in Women with Breast Cancer. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Adjuvant Hormonotherapy and Cardiovascular Risk in Post-Menopausal Women with Breast Cancer: A Large Population-Based Cohort Study. [2021]

7. Italy pubmed.ncbi.nlm.nih.gov

[Hormone therapy, cardio-metabolic profile and cardiotoxicity. Still a dark side of cardio-oncology. Part 1: Breast cancer]. [2022]