Hormone Therapy for Cardiovascular Health in Breast Cancer Patients

(CROWN Trial)

Recruiting in Palo Alto (17 mi)

+2 other locations

Overseen by Alexandra Thomas, MD

Age: 18 - 65

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Duke University

Must be taking: Aromatase inhibitors, SERD

Disqualifiers: Pregnancy, Cardiac arrhythmia, Uncontrolled illness, others

No Placebo Group

Trial Summary

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.

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 3 4 5}

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 4 5 6}

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 7}

Research Team

Alexandra Thomas, MD

Principal Investigator

Duke University

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Near-Complete Estrogen Deprivation Therapy (Hormone 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.

Participant Groups

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.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Duke Cancer Center Durham, NC

Virginia Commonwealth University Massey Cancer Center Richmond, VA

Wake Forest Baptist Comprehensive Cancer Center Winston-Salem, NC

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2495

Patients Recruited

5,912,000+

Wake Forest University Health Sciences

Lead Sponsor

Trials

1432

Patients Recruited

2,506,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3987

Patients Recruited

47,860,000+

National Cancer Institute (NCI)

Collaborator

Trials

14080

Patients Recruited

41,180,000+

Findings from Research

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]

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]

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]

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]

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]

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]

References

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]