Clinical trial NCT06776458: Chronic Impacts of Endocrine Therapy on Cardiovascular and Brain Health Outcomes in Breast Cancer
Official title: Beyond Cardiotoxicity: Characterizing the Long-term Cardiovascular Side Effects of Breast Cancer Endocrine Treatment
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Breast Cancer Females
Keywords: Aromatase Inhibitors
Breast Cancer Females
Heart Disease Risk Factors
Lead sponsor: University of Toronto
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: Cancer Research Society
First posted: 2025-01-15
Enrollment: 112
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: Participants will be recruited from the community in the Greater Toronto Area via posters, newsletters, social media advertisements, and word of mouth.

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.


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

Primary outcomes:
measure: Aortic Stiffness
timeFrame: Day 2 (In-Person Session)
Secondary outcomes:
measure: Brachial Artery Endothelial Function
timeFrame: Day 2 (In-Person Session)
measure: Carotid Artery Stiffness
timeFrame: Day 2 (In-Person Session)
measure: Carotid Intima Media Thickness
timeFrame: Day 2 (In-Person Session)
measure: Arterial Stiffness
timeFrame: Day 2 (In-Person Session)
measure: Left Ventricular Ejection Fraction (LVEF)
timeFrame: Day 2 (In-Person Session)
measure: Global Longitudinal Strain
timeFrame: Day 2 (In-Person Session)
measure: Left Ventricular Diastolic Function
timeFrame: Day 2 (In-Person Session)
measure: Cerebrovascular Response
timeFrame: Day 2 (In-Person Session)
measure: Brain derived neurotrophic factor
timeFrame: Day 2 (In-Person Session)
measure: Lipid profile
timeFrame: Day 2 (In-Person Session)
measure: Hemoglobin A1c
timeFrame: Day 2 (In-Person Session)
measure: Insulin resistance
timeFrame: Day 2 (In-Person Session)
measure: Protein metabolism
timeFrame: Day 1 (At-Home Session)
Other outcomes:
measure: Cardiorespiratory fitness
timeFrame: Day 2 (In-Person Session)
measure: Framingham 10-year risk (%)
timeFrame: Day 2 (In-Person Session)
measure: Heart Rate Recovery
timeFrame: Day 2 (In-Person Session)
measure: Heart Rate Variability
timeFrame: Day 2 (In-Person Session)
measure: avO2 difference
timeFrame: Day 2 (In-Person Session)
measure: Cardiac Output
timeFrame: Day 2 (In-Person Session)
measure: Stroke Volume
timeFrame: Day 2 (In-Person Session)
measure: Resting Blood Pressure
timeFrame: Day 2 (In-Person Session)
measure: Beat-by-beat Blood Pressure
timeFrame: Day 2 (In-Person Session)
measure: Hemoglobin
timeFrame: Day 2 (In-Person Session)
measure: Whole-body fat and fat-free mass
timeFrame: Day 2 (In-Person Session)
measure: Body circumferences
timeFrame: Day 2 (In-Person Session)
measure: Bone Mineral Density
timeFrame: Day 2 (In-Person Session)
measure: Body weight
timeFrame: Day 2 (In-Person Session)
measure: Body mass index (BMI)
timeFrame: Day 2 (In-Person Session)
measure: Dietary intake
timeFrame: Day 1 (At-Home Session)
measure: Diet quality
timeFrame: Day 1 (At-Home Session)
measure: Depression & Anxiety
timeFrame: Day 1 (At-Home Session)
measure: Autonomic symptoms
timeFrame: Day 1 (At-Home Session)
measure: Cognitive Function: Verbal Fluency
timeFrame: Day 2 (In-Person Session)
measure: Cognitive Function: Verbal Learning & Memory
timeFrame: Day 2 (In-Person Session)
measure: Cognitive Function: Processing Speed
timeFrame: Day 2 (In-Person Session)
measure: Cognitive Impairment
timeFrame: Day 2 (In-Person Session)
measure: Cancer-specific Quality of life (only measured in cancer group)
timeFrame: Day 1 (At-Home Session)
measure: Musculoskeletal health
timeFrame: Day 1 (At-Home Session)
measure: Musculoskeletal pain
timeFrame: Day 1 (At-Home Session)
measure: Musculoskeletal osteoarthritis risk
timeFrame: Day 1 (At-Home Session)
measure: Musculoskeletal disability
timeFrame: Day 1 (At-Home Session)
measure: Cardiovascular risk
timeFrame: Day 1 (At-Home Session)
measure: Gender Factors
timeFrame: Day 1 (At-Home Session)
measure: Health-related quality of life
timeFrame: Day 1 (At-Home Session)
measure: Psychosocial stress
timeFrame: Day 1 (At-Home Session)
measure: Sleep quality - subjective
timeFrame: Day 1 (At-Home Session)
measure: Sleep quantity and quality - device measured
timeFrame: Day 1 (At-Home Session)
measure: Physical activity
timeFrame: Day 1 (At-Home Session)
measure: Sedentary time
timeFrame: Day 1 (At-Home Session)
Locations:
city: Toronto
country: Canada
facility: University of Toronto
state: Ontario
Study officials:
References: