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| Name | Class |
|---|---|
| Canadian Institutes of Health Research (CIHR) | OTHER_GOV |
| Cancer Research Society | OTHER |
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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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Aromatase Inhibitors (1 year) | Breast cancer patients at 1-year post-diagnosis, who were treated with aromatase inhibitors |
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| Aromatase Inhibitors (5 year) | Breast cancer patients at 5-year post-diagnosis, who were treated with aromatase inhibitors |
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| Aromatase Inhibitors (10 years) | Breast cancer patients at 10-years post-diagnosis, who were treated with aromatase inhibitors |
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| 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) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| N/A - Usual Care | Other | Breast cancer survivors will have received usual care aromatase inhibitors for up to 10 years post-diagnosis. |
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| Measure | Description | Time Frame |
|---|---|---|
| Aortic Stiffness | Aortic stiffness, measured non-invasively by pulse wave velocity, will be assessed using applanation tonometry. | Day 2 (In-Person Session) |
| Measure | Description | Time Frame |
|---|---|---|
| Brachial Artery Endothelial Function | Endothelial function will be assessed using the gold standard method of flow mediated dilation (FMD) using non-invasive duplex ultrasound (GE Vivid IQ) and edge-tracking software. | Day 2 (In-Person Session) |
| Carotid Artery Stiffness |
| Measure | Description | Time Frame |
|---|---|---|
| Cardiorespiratory fitness | Measured as peak volume of oxygen consumption via indirect calorimetry during a cardiopulmonary exercise test on a cycle ergometer. | Day 2 (In-Person Session) |
| Framingham 10-year risk (%) |
Inclusion Criteria:
Case group:
Control group:
Exclusion Criteria:
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Participants will be recruited from the community in the Greater Toronto Area via posters, newsletters, social media advertisements, and word of mouth.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Amy A. Kirkham, PhD | Contact | 416-946-4069 | amy.kirkham@utoronto.ca |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Toronto | Recruiting | Toronto | Ontario | M5S2C9 | Canada |
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Participant blood samples will be collected, analyzed, and stored according to study protocol.
Functional assessment of the carotid artery stiffness will be assessed using B-mode ultrasound and artery edge-tracking software |
| Day 2 (In-Person Session) |
| Carotid Intima Media Thickness | Structural assessment of the carotid artery thickness will be assessed using B-mode ultrasound and artery edge-tracking software | Day 2 (In-Person Session) |
| Arterial Stiffness | Measured by Pulse Wave Velocity (PWV) of the arm and leg | Day 2 (In-Person Session) |
| Left Ventricular Ejection Fraction (LVEF) | Cardiac outcomes will be assessed via echocardiography (GE Vivid IQ) and analyzed using Echopac software, represented as a % using the following formula: stroke volume/end diastolic volume x 100%. | Day 2 (In-Person Session) |
| Global Longitudinal Strain | Cardiac outcomes will be assessed via echocardiography (GE Vivid IQ) and analyzed using Echopac software, expressed as a percentage of the relative change in length of the left ventricle through a cardiac cycle. | Day 2 (In-Person Session) |
| Left Ventricular Diastolic Function | Cardiac outcomes will be assessed via echocardiography (GE Vivid IQ) and analyzed using Echopac software, assessed by the ratio of peak early diastolic velocity to peak mitral valve velocity (E/A ratio). | Day 2 (In-Person Session) |
| Cerebrovascular Response | Cerebral blood flow velocity response (delta change compared to rest) of the middle cerebral artery will be assessed using transcranial Doppler ultrasound (Neurovision Transcranial Doppler System Model 500M) in accordance with recent guidelines, in response to postural changes (sit-to-stand) and exercise (squatting). | Day 2 (In-Person Session) |
| Brain derived neurotrophic factor | Brain derived neurotrophic factor will be assessed via fasted venipuncture using in-house assays. | Day 2 (In-Person Session) |
| Lipid profile | HDL, LDL, total Cholesterol, Triglycerides analyzed from blood serum using a clinical assay at a core lab. | Day 2 (In-Person Session) |
| Hemoglobin A1c | Analyzed from blood plasma using a clinical assay at a core lab. | Day 2 (In-Person Session) |
| Insulin resistance | Calculated as Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) from fasting blood measures of glucose and insulin, analyzed using a clinical assay at a core lab. | Day 2 (In-Person Session) |
| Protein metabolism | Analyzed from breathing test and urine sample before and after the participant consume a test protein drink. | Day 1 (At-Home Session) |
Calculated using the standardized scoring system where sex-specific points are assigned to age, systolic blood pressure (dependent on treatment status), HDL, total cholesterol, smoking and diabetes status. The range for females is 0-30% where a higher score indicates a greater risk of cardiovascular disease in the next 10 years.
| Day 2 (In-Person Session) |
| Heart Rate Recovery | Measured as the difference between peak heart rate during the cardiorespiratory fitness test and heart rate 2-minutes into active recovery after stopping the exercise test. | Day 2 (In-Person Session) |
| Heart Rate Variability | Measured as the variability in beat-to-beat heart rate during supine rest. | Day 2 (In-Person Session) |
| avO2 difference | Measured by a non-invasive optical technique used to assess tissue oxygenation and hemodynamics (Near-Infrared Spectroscopy - NIRS) at rest, and during cycling exercise at ventilatory threshold, respiratory compensation point, and peak oxygen uptake. | Day 2 (In-Person Session) |
| Cardiac Output | Measured continuously by a finger cuff (Finger Arterial Pressure - Finapres) at rest, and during cycling exercise at ventilatory threshold, respiratory compensation point, and peak oxygen uptake. | Day 2 (In-Person Session) |
| Stroke Volume | Measured continuously by a finger cuff (Finger Arterial Pressure - Finapres) at rest, and during cycling exercise at ventilatory threshold, respiratory compensation point, and peak oxygen uptake. | Day 2 (In-Person Session) |
| Resting Blood Pressure | Measured as the average of the last 5 of 6 blood pressure measurements taken 60 seconds apart using an automatic blood pressure device. | Day 2 (In-Person Session) |
| Beat-by-beat Blood Pressure | Measured continuously by a finger cuff (Finger Arterial Pressure - Finapres) at rest, and during cycling exercise at ventilatory threshold, respiratory compensation point, and peak oxygen uptake. | Day 2 (In-Person Session) |
| Hemoglobin | Analyzed from blood plasma using a clinical assay at a core lab. | Day 2 (In-Person Session) |
| Whole-body fat and fat-free mass | Measured using a body composition device (BodPod) to estimate whole body fat (in kg and %) and fat free mass (in kg and %). | Day 2 (In-Person Session) |
| Body circumferences | Circumferences of the waist, hip and neck, measured using an inelastic tape | Day 2 (In-Person Session) |
| Bone Mineral Density | Assessed using a dual x-ray absorptiometry scan. | Day 2 (In-Person Session) |
| Body weight | Assessed fasted in lab using a calibrated scale | Day 2 (In-Person Session) |
| Body mass index (BMI) | Calculated from a measurement of height using a stadiometer and body weight (detailed above). | Day 2 (In-Person Session) |
| Dietary intake | Various components of dietary intake including macronutrients and micronutrients will be assessed through 3-day food records over 2 weekdays and 1 weekend collected using ASA-24 online system. | Day 1 (At-Home Session) |
| Diet quality | An overall measure of alignment with Canada's dietary guidelines measured via the Healthy Eating Food Index-2019 calculated from 3-day diet records | Day 1 (At-Home Session) |
| Depression & Anxiety | Measured by the Hospital Anxiety and Depression Scale (HADS); score ranges from 0-21 for each of depression and anxiety with a higher score indicating more severe depression or anxiety | Day 1 (At-Home Session) |
| Autonomic symptoms | Assessed by the COMPASS 31 (Composite Autonomic Symptom Score) questionnaire. This questionnaire provides clinically relevant scores of autonomic symptom severity. Scores range from 0 to 31 with questions in six domains: orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor, with a higher scoring indicating worse autonomic dysfunction. | Day 1 (At-Home Session) |
| Cognitive Function: Verbal Fluency | Assessed using the Controlled Oral Word Association of the Multilingual Aphasia Exam (verbal fluency), with higher number of words produced indicative of better cognitive health. | Day 2 (In-Person Session) |
| Cognitive Function: Verbal Learning & Memory | Assessed the Hopkins Verbal Learning Test (learning, memory) with an immediate recall, delayed recall, and recognition accuracy from a list of 12 words. Higher number of words are indicative of better cognitive health. | Day 2 (In-Person Session) |
| Cognitive Function: Processing Speed | Assessed by the Trail Making Test (attention, speed, executive function). Shorter test time on 2 forms of the test is indicative of better cognitive health. | Day 2 (In-Person Session) |
| Cognitive Impairment | Assessed by Global Deficit Score (GDS). GDS is calculated as an average score from 3 tests: 1) Hopkins Verbal Learning Test (learning, memory), 2) Trail Making Test (attention, speed, executive function), 3) Controlled Oral Word Association of the Multilingual Aphasia Exam (verbal fluency). Each subtest of the GDS has a complex scoring system, detailed above, with higher values indicating greater cognitive deficits. | Day 2 (In-Person Session) |
| Cancer-specific Quality of life (only measured in cancer group) | Assessed using the Functional Assessment of Cancer Therapy - General (FACT-G), - Endocrine (FACT-ES), Cognitive (FACT-Cog) and - Fatigue (FACT-F). These are patient-reported outcome measurements used to assess health-related quality of life in patients with a history of cancer. The FACT-G is calculated from the sum of four subscales on general health related quality of life with a range of 0-108 points. The FACT-ES is a score of 19 questions with scores ranging from 0-76. The FACT-Cog contains 37 questions with a score of 0 to 132. FACT-F is calculated from the sum of 13 questions. Higher scores on each scale is indicative of better quality of life. | Day 1 (At-Home Session) |
| Musculoskeletal health | Assessed using the Musculoskeletal Health Questionnaire (MSK-HQ). The MSK-HQ is a series of 15 questions with a range from 0-56 with higher scores being indicative of poorer MSK health. | Day 1 (At-Home Session) |
| Musculoskeletal pain | Assessed using the Brief Pain Inventory (BPI). The BPI is scored as the average of seven pain-related questions with a range of 0-10 with higher scores representing greater pain. | Day 1 (At-Home Session) |
| Musculoskeletal osteoarthritis risk | Assessed using the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index. The WOMAC is a series of 17 questions resulting in a % (0-100) with higher scores indicative of greater osteoarthritis index. | Day 1 (At-Home Session) |
| Musculoskeletal disability | Assessed using the Disabilities of the Arm, Shoulder, and Hand (DASH) Questionnaire. The DASH contains 30 questions with scores of 0 to 100 with higher scores representing higher severity in disability. | Day 1 (At-Home Session) |
| Cardiovascular risk | Assessed using the INTERHEART Risk Score, a validated score for quantifying risk-factor burden without the use of laboratory testing (with higher scores indicating greater risk-factor burden). | Day 1 (At-Home Session) |
| Gender Factors | Assessed by the Stanford Gender-related Variables for Health Research (GVHR) which includes questions related to seven gender-related variables: caregiver strain, work strain, independence, risk-taking, emotional intelligence, social support, and discrimination. | Day 1 (At-Home Session) |
| Health-related quality of life | Assessed by RAND-36, where an independent score is provided for 8 scales ranging from 0 to 100 and 2 component summary scales ranging from 0-50 with a higher score indicating better quality of life. | Day 1 (At-Home Session) |
| Psychosocial stress | Assessed by the perceived stress scale (PSS-14) where individual scores can range from 0 to 56 with higher scores indicating higher perceived stress | Day 1 (At-Home Session) |
| Sleep quality - subjective | Subjectively assessed by the Pittsburgh Sleep Quality Index (PQSI), which measures components of sleep: sleep duration, disturbance, sleep latency, daytime dysfunction due to sleepiness, sleep efficiency, overall sleep quality, and sleep medication use, with higher scores reflecting poorer sleep quality. From these 7 questions, a global score of 0 to 21 is created with higher values indicative of poorer sleep quality. | Day 1 (At-Home Session) |
| Sleep quantity and quality - device measured | Measured via Garmin smartwatch for the total sleep duration and efficiency. | Day 1 (At-Home Session) |
| Physical activity | Measured via Garmin smartwatch for time in moderate-vigorous physical activity, and step counts. | Day 1 (At-Home Session) |
| Sedentary time | Measured via Garmin smartwatch for time spent sitting. | Day 1 (At-Home Session) |