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

NCT06776458 | Recruiting

• 1 other identifier: REB #46819
• Study Type: observational
• Target: 112
• Locations: 1 country
• Sites: 1

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. 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. 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. 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. 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.

Conditions

Breast Cancer Females

Keywords

Aromatase Inhibitors; Breast Cancer Females; Heart Disease Risk Factors

Outcome Measures

Primary Outcomes (1)

• Aortic Stiffness

  Aortic stiffness, measured non-invasively by pulse wave velocity, will be assessed using applanation tonometry.

  Day 2 (In-Person Session)

Secondary Outcomes (13)

• Brachial Artery Endothelial Function

  Day 2 (In-Person Session)

• Carotid Artery Stiffness

  Day 2 (In-Person Session)

• Carotid Intima Media Thickness

  Day 2 (In-Person Session)

• Arterial Stiffness

  Day 2 (In-Person Session)

• Left Ventricular Ejection Fraction (LVEF)

  Day 2 (In-Person Session)

Other Outcomes (36)

• Cardiorespiratory fitness

  Day 2 (In-Person Session)

• Framingham 10-year risk (%)

  Day 2 (In-Person Session)

• Heart Rate Recovery

  Day 2 (In-Person Session)

Study Arms (6)

Aromatase Inhibitors (1 year)

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

Other: N/A - Usual Care

Aromatase Inhibitors (5 year)

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

Other: N/A - Usual Care

Aromatase Inhibitors (10 years)

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

Other: N/A - Usual Care

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)

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)

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)

Interventions

N/A - Usual Care OTHER

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

Aromatase Inhibitors (1 year); Aromatase Inhibitors (10 years); Aromatase Inhibitors (5 year)

Eligibility Criteria

• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants will be recruited from the community in the Greater Toronto Area via posters, newsletters, social media advertisements, and word of mouth.

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Toronto: lead
• Canadian Institutes of Health Research (CIHR): collaborator
• Cancer Research Society: collaborator

Study Sites (1)

University of Toronto

Toronto, Ontario, M5S2C9, Canada

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Participant blood samples will be collected, analyzed, and stored according to study protocol.

Central Study Contacts

Amy A. Kirkham, PhD

CONTACT

416-946-4069; amy.kirkham@utoronto.ca

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: December 30, 2024
• First Posted: January 15, 2025
• Study Start: February 1, 2025
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: January 15, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)