Short-term Impacts of Endocrine Therapy on Cardiovascular and Brain Health Outcomes in Breast Cancer

NCT06781762 | Recruiting

• 1 other identifier: REB #46818
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Aromatase inhibitors are the most used endocrine therapy for hormone-positive breast cancer. While there is a clear linear relationship between the duration of aromatase inhibitor use and the cumulative incidence of cardiovascular events and mortality, the underlying mechanisms contributing to this risk remain unknown. This study will characterize the short-term effects of aromatase inhibitor therapy on established and novel health indices for cardiovascular diseases in breast cancer patients. Using a longitudinal case-control design this study will assess the effects of short-term (first 6 months) aromatase inhibitor use in breast cancer patients compared to age- and BMI-matched controls, aiming to determine the cardiovascular, metabolic, and behavioural health impacts of endocrine treatment during this early period. 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 blood biomarkers (lipids), blood pressure, aortic and peripheral stiffness, carotid artery stiffness and intima media thickness, endothelial function, and left ventricular ejection fraction, longitudinal strain, volumes, and mass, including the responsiveness of the cardiovascular system to an oral glucose tolerance test, 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 and bone mineral density, along with assessments of glycemic regulation in response to an oral glucose tolerance test and in 24h periods of free-living (continuous glucose monitoring), 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; Obesity

Outcome Measures

Primary Outcomes (1)

• Aortic Stiffness

  Aortic stiffness, measured non-invasively by pulse wave velocity, will be assessed using applanation tonometry. Measurements will be taken at rest and every 30min during a 2h oral glucose tolerance test.

  Baseline, 6 months

Secondary Outcomes (12)

• Brachial Artery Endothelial Function

  Baseline, 6 months

• Carotid Artery Stiffness

  Baseline, 6 months

• Carotid Intima Media Thickness

  Baseline, 6 months

• Left Ventricular Ejection Fraction (LVEF)

  Baseline, 6 months

• Global Longitudinal Strain

  Baseline, 6 months

Other Outcomes (44)

• Cardiorespiratory fitness

  Baseline, 6 months

• Framingham 10-year cardiovascular risk (%)

  Baseline, 6 months

• Heart Rate Recovery

  Baseline, 6 months

Study Arms (2)

Breast Cancer Patients Receiving Aromatase Inhibitor

Breast Cancer patients using aromatase inhibitors for 6 months

Other: N/A (Usual Care)

Matched Non-Cancer Controls

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

Interventions

N/A (Usual Care) OTHER

BC survivors will be using aromatase inhibitors as prescribed in their usual care treatment.

Breast Cancer Patients Receiving Aromatase Inhibitor

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

Case participants will be recruited from Princess Margaret Cancer Centre in Toronto. Control participants will be local participants in the greater Toronto area, recruited through 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
• Confirmed to start aromatase inhibitor therapy for the first time in next 2-3 months
• 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
• Cancer Research Society: collaborator
• Canadian Institutes of Health Research (CIHR): collaborator
• Princess Margaret Hospital, Canada: collaborator

Study Sites (1)

University of Toronto

Toronto, Ontario, M5S2C9, Canada

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples will be collected and used for biochemical analysis outlined in the study protocol.

MeSH Terms

Conditions

Obesity

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

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 17, 2025
• Study Start: June 6, 2025
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: October 1, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)