Chronic Impacts of Endocrine Therapy on Cardiovascular and Brain Health Outcomes in Breast Cancer

NCT ID: NCT06776458

Last Updated: 2025-01-15

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 112 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-02-01
• Study Completion Date: 2026-09-30

Brief Summary

Aromatase inhibitors are the most used endocrine therapy for hormone-positive breast cancer. Despite the evidence that aromatase inhibitor therapy is associated with increased risk of cardiovascular events, potentially related to the duration of use, no studies have been conducted to characterize the long-term effects of aromatase inhibitor therapy on the heart or vessel structure and function as underlying determinants of cardiovascular mortality. This study will characterize the long-term effects of aromatase inhibitor therapy on established and novel health indices for CVD in breast cancer patients, by examining cross-sectionally compare health indices 1-, 5- and 10-years post-diagnosis in breast cancer survivors to controls. Specifically, our objectives are as follows:

1. To examine the effects of aromatase inhibitor therapy on early risk indicators for cardiovascular disease in the peripheral vasculature and heart, including aortic stiffness (primary outcome) and secondary outcomes of peripheral and carotid artery stiffness, blood biomarkers (lipids), blood pressure, carotid intima media thickness, endothelial function, and left ventricular ejection fraction, global longitudinal strain, and left ventricular diastolic function, in breast cancer survivors compared to controls.

2. To examine the effects of aromatase inhibitor therapy on factors related to cerebrovascular health, autonomic regulation, and cognitive function, including BDNF, heart rate variability, cerebrovascular function in response to a supine-sit-stand maneuver and squatting challenge, and a core battery of cognitive function tests, in breast cancer survivors compared to controls.

3. To examine the effects of aromatase inhibitor therapy on body composition, bone mineral density, and protein metabolism, in breast cancer survivors compared to controls.

4. To examine the effects of aromatase inhibitor therapy on lifestyle factors (behavioural), including diet, physical activity (including cardiorespiratory fitness), sleep, stress, and quality of life, in breast cancer survivors compared to controls.

The investigators hypothesize that biologic and behavioural cardiovascular health indices will be deteriorated relative to controls as early as 1 year post-diagnosis and that prolonged use will further accelerate aging-related impairments.

Conditions

Breast Cancer Females

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Aromatase Inhibitors (1 year)

Breast cancer patients at 1-year post-diagnosis, who were treated with aromatase inhibitors

N/A - Usual Care

Intervention Type: OTHER

Breast cancer survivors will have received usual care aromatase inhibitors for up to 10 years post-diagnosis.

Aromatase Inhibitors (5 year)

Breast cancer patients at 5-year post-diagnosis, who were treated with aromatase inhibitors

N/A - Usual Care

Intervention Type: OTHER

Breast cancer survivors will have received usual care aromatase inhibitors for up to 10 years post-diagnosis.

Aromatase Inhibitors (10 years)

Breast cancer patients at 10-years post-diagnosis, who were treated with aromatase inhibitors

N/A - Usual Care

Intervention Type: OTHER

Breast cancer survivors will have received usual care aromatase inhibitors for up to 10 years post-diagnosis.

Matched Controls (1 year)

A woman without a history of cancer will be recruited to match each breast cancer patient will be matched on age and BMI (within 3 years and 3 kg/m2, whenever possible)

No interventions assigned to this group

Matched Controls (5 years)

A woman without a history of cancer will be recruited to match each breast cancer patient will be matched on age and BMI (within 3 years and 3 kg/m2, whenever possible)

No interventions assigned to this group

Matched Controls (10 years)

A woman without a history of cancer will be recruited to match each breast cancer patient will be matched on age and BMI (within 3 years and 3 kg/m2, whenever possible)

No interventions assigned to this group

Interventions

N/A - Usual Care

Breast cancer survivors will have received usual care aromatase inhibitors for up to 10 years post-diagnosis.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

Case group:

• Biologically female
• Post-menopausal with natural (no bilateral oophorectomy) amenorrhea for at least 1 year
• If using hormone replacement therapy, limit of a maximum of 3 years of treatment but not within the last 6 months.
• Diagnosis of stage I, II, or III breast cancer
• Hormone receptor positive breast cancer
• HER negative (ER+/PR+/HER-) breast cancer
• Breast cancer patients ~1 post-diagnosis who have received aromatase inhibitor therapy
• Breast cancer patients ~5 and ~10 years post-diagnosis who have received aromatase inhibitor therapy for at least 2 years
• Received surgery/radiation therapies

Control group:

• Biologically female
• Post-menopausal with natural (no bilateral oophorectomy) amenorrhea for at least 1 year
• If using hormone replacement therapy, limit of a maximum of 3 years of treatment but not within the last 6 months.

Exclusion Criteria

• Previous treatment using tamoxifen endocrine therapy in a pre-or peri-menopausal setting
• Major signs or symptoms of cardiovascular diseases, diabetes, or renal disease (taken from the American College of Sports Medicine's Guidelines for Exercise Testing and Prescription 11th edition Table 2.1: pain or discomfort in the chest, neck, jaw, arms with rest or exercise, shortness of breath at rest or with mild exertion, dizziness or syncope, loss of balance or passing out, ankle edema, palpitations or tachycardia, intermittent claudication, known heart murmur, unusual fatigue with usual activities.)
• American Heart Association's absolute or relative contraindications for symptom-limited maximal exercise testing (myocardial infarction, aortic or coronary artery stenosis, heart failure, pulmonary embolism or deep vein thrombosis, inflammation of the heart (myocarditis, pericarditis, and/or endocarditis), uncontrolled cardiac arrythmia, advanced or complete electrical heart block, stroke or transient ischemia attack, blood pressure >200mmHg/100mmHg, a cancer diagnosis other than skin cancer)
• Unable to provide informed consent or communicate in English
• Mobility limitations to exercise testing (i.e., wheelchair, walker use, limp impeding walking)
• Extreme claustrophobia

• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Cancer Research Society

OTHER

Sponsor Role: collaborator

University of Toronto

OTHER

Sponsor Role: lead

Responsible Party

Amy Kirkham

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Toronto

Toronto, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Amy A. Kirkham, PhD

Role: CONTACT

amy.kirkham@utoronto.ca

416-946-4069

Facility Contacts

Amy A. Kirkham, PhD

Role: primary

amy.kirkham@utoronto.ca

416-946-4069

Amy A. Kirkham, PhD

Role: backup

Other Identifiers

REB #46819

Identifier Type: -

Identifier Source: org_study_id