Recruiting

Observational Study

Sponsor:

University of Toronto

Code:

NCT06776458

Conditions

Breast Cancer Females

Eligibility Criteria

Sex: Female

Age: 0+

Healthy Volunteers: Accepted

Interventions

N/A - Usual Care

Study Details

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 ID

NCT06776458

Start date

Feb 1, 2025

Status verified date

Jan, 2025

Completion date

Sep 30, 2026

Anticipated

Primary completion date

Sep 30, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: Female

Age: 0+

Healthy Volunteers: Accepted

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

Study Design

Enrollment

112 participants

Anticipated

Interventions and Outcome Measures

Arms

Aromatase Inhibitors (1 year)

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

Aromatase Inhibitors (5 year)

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

Aromatase Inhibitors (10 years)

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

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

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

Primary outcome measure

  • Aortic Stiffness [ Time Frame: Day 2 (In-Person Session) ]

Central Contacts and Locations

Central contacts

Amy A. Kirkham, PhD

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

Locations

University of Toronto

Recruiting

Toronto, Ontario, Canada, M5S2C9

Contacts

Amy A. Kirkham, PhD

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

More Information

Sponsor

University of Toronto

Last update posted

Jan 15, 2025

Last verified

Jan, 2025

Keywords

  • Aromatase Inhibitors
  • Breast Cancer Females
  • Heart Disease Risk Factors

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-24. This information was provided to ClinicalTrials.gov by University of Toronto on 2025-01-15. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.