Clinical trial NCT06781762: Short-term Impacts of Endocrine Therapy on Cardiovascular and Brain Health Outcomes in Breast Cancer
Official title: Beyond Cardiotoxicity: Characterizing the Short-term Cardiovascular Side Effects of Breast Cancer Endocrine Treatment
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Breast Cancer Females
Keywords: Aromatase Inhibitors
Breast Cancer Females
Heart Disease Risk Factors
Obesity
Lead sponsor: University of Toronto
Sponsor class: OTHER
Collaborators: name: Cancer Research Society
name: Canadian Institutes of Health Research (CIHR)
name: UHN - Princess Margaret Cancer Centre, Toronto, Canada
First posted: 2025-01-17
Enrollment: 40
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

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. 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. 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 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. 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 cardiovascular and metabolic health outcomes will be similar between breast cancer survivors and controls at baseline but will deteriorate relative to controls within the first 6 months of aromatase inhibitor therapy.


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
* 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.

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

Primary outcomes:
measure: Aortic Stiffness
timeFrame: Baseline, 6 months
Secondary outcomes:
measure: Brachial Artery Endothelial Function
timeFrame: Baseline, 6 months
measure: Carotid Artery Stiffness
timeFrame: Baseline, 6 months
measure: Carotid Intima Media Thickness
timeFrame: Baseline, 6 months
measure: Left Ventricular Ejection Fraction (LVEF)
timeFrame: Baseline, 6 months
measure: Global Longitudinal Strain
timeFrame: Baseline, 6 months
measure: Left Ventricular Diastolic Function
timeFrame: Baseline, 6 months
measure: Arterial Stiffness
timeFrame: Baseline, 6 months
measure: Cerebrovascular Response
timeFrame: Baseline, 6 months
measure: Brain Derived Neurotrophic Factor
timeFrame: Baseline, 6 months
measure: Lipid profile
timeFrame: Baseline, 6 months
measure: Hemoglobin A1c
timeFrame: Baseline, 6 months
measure: Insulin resistance
timeFrame: Baseline, 6 months
Other outcomes:
measure: Cardiorespiratory fitness
timeFrame: Baseline, 6 months
measure: Framingham 10-year cardiovascular risk (%)
timeFrame: Baseline, 6 months
measure: Heart Rate Recovery
timeFrame: Baseline, 6 months
measure: Heart Rate Variability
timeFrame: Baseline, 6 months
measure: avO2 difference
timeFrame: Baseline, 6 months
measure: Cardiac Output
timeFrame: Baseline, 6 months
measure: Stroke Volume
timeFrame: Baseline, 6 months
measure: Resting Blood Pressure
timeFrame: Baseline, 6 months
measure: Beat-by-beat Blood Pressure
timeFrame: Baseline, 6 months
measure: Glucose Levels
timeFrame: Baseline, 6 months
measure: Hemoglobin
timeFrame: 6 months
measure: Whole-body fat mass
timeFrame: Baseline, 6 months
measure: Whole-body fat-free mass
timeFrame: Baseline, 6 months
measure: Waist Circumference
timeFrame: Baseline, 6 months
measure: Hip Circumference
timeFrame: Baseline, 6 months
measure: Neck Circumference
timeFrame: Baseline, 6 months
measure: Body weight
timeFrame: Baseline, 6 months
measure: Body mass index (BMI)
timeFrame: Baseline, 6 months
measure: Dietary intake
timeFrame: Baseline, 6 months
measure: Diet quality
timeFrame: Baseline, 6 months
measure: Depression & Anxiety
timeFrame: Baseline, 6 months
measure: Autonomic symptoms
timeFrame: Baseline, 6 months
measure: Cognitive Function: Verbal Fluency
timeFrame: Baseline, 6 months
measure: Cognitive Function: Verbal Learning & Memory
timeFrame: Baseline, 6 months
measure: Cognitive Function: Processing Speed
timeFrame: Baseline, 6 months
measure: Cognitive Impairment (Composite Measure)
timeFrame: Baseline, 6 months
measure: Cancer-specific Quality of life (only assessed in cancer group): General
timeFrame: Baseline, 6 months
measure: Cancer-specific Quality of life (only assessed in cancer group): Endocrine
timeFrame: Baseline, 6 months
measure: Cancer-specific Quality of life (only assessed in cancer group): Cognitive
timeFrame: Baseline, 6 months
measure: Cancer-specific Quality of life (only assessed in cancer group): Fatigue
timeFrame: Baseline, 6 months
measure: Musculoskeletal health
timeFrame: Baseline, 6 months
measure: Musculoskeletal pain
timeFrame: Baseline, 6 months
measure: Musculoskeletal osteoarthritis risk
timeFrame: Baseline, 6 months
measure: Musculoskeletal disability
timeFrame: Baseline, 6 months
measure: Cardiovascular risk
timeFrame: Baseline, 6 months
measure: Gender-Related Factors
timeFrame: Baseline
measure: Health-related quality of life
timeFrame: Baseline, 6 months
measure: Psychosocial stress
timeFrame: Baseline, 6 months
measure: Sleep quality - subjective
timeFrame: Baseline, 6 months
measure: Sleep quantity - device measured
timeFrame: Baseline, 6 months
measure: Sleep quality - device measured
timeFrame: Baseline, 6 months
measure: Moderate-Vigorous Physical Activity
timeFrame: Baseline, 6 months
measure: Physical activity: step counts
timeFrame: Baseline, 6 months
measure: Sedentary time
timeFrame: Baseline, 6 months
Locations:
city: Toronto
country: Canada
facility: University of Toronto
state: Ontario
Study officials:
References: