Breast Cancer FemalesSTRIVE-ChronicNCT06776458
Chronic Impacts of Endocrine Therapy on Cardiovascular and Brain Health Outcomes in Breast Cancer
An observational study of Breast Cancer Females, run by University of Toronto at 1 site in Canada.
Trial 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… Read more about this study
- Who is it for?
- Any age, women onlyHealthy volunteers can take part
- Conditions the study is for
- Breast Cancer Females
- How many people
- 112 participants
- Where
- 1 siteCanada
- Study dates
- 1 Feb 2025to 30 Sep 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Women only
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Participants will be recruited from the community in the Greater Toronto Area via posters, newsletters, social media advertisements, and word of mouth.
Who may be able to join
- 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
Show all 14Show fewer
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
University of Toronto
Toronto, Ontario, M5S2C9
Amy A. Kirkham, PhD, 416-946-4069, amy.kirkham@utoronto.ca
Amy A. Kirkham, PhD
About this study
Official title: Beyond Cardiotoxicity: Characterizing the Long-term Cardiovascular Side Effects of Breast Cancer Endocrine Treatment
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:
- 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.
- 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.
- To examine the effects of aromatase inhibitor therapy on body composition, bone mineral density, and protein metabolism, in breast cancer survivors compared to controls.
- 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
- Being tested
- N/A - Usual Care
- Keywords
- Aromatase Inhibitors, Breast Cancer Females, Heart Disease Risk Factors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N/A - Usual CareOther
Breast cancer survivors will have received usual care aromatase inhibitors for up to 10 years post-diagnosis.
| Study group | Role | What they receive |
|---|---|---|
| Aromatase Inhibitors (1 year) | Breast cancer patients at 1-year post-diagnosis, who were treated with aromatase inhibitors Receives: Other: N/A - Usual Care | |
| Aromatase Inhibitors (5 year) | Breast cancer patients at 5-year post-diagnosis, who were treated with aromatase inhibitors Receives: Other: N/A - Usual Care | |
| Aromatase Inhibitors (10 years) | Breast cancer patients at 10-years post-diagnosis, who were treated with aromatase inhibitors Receives: Other: N/A - Usual Care | |
| 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) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Aortic Stiffness
Aortic stiffness, measured non-invasively by pulse wave velocity, will be assessed using applanation tonometry.
Measured: Day 2 (In-Person Session)
Secondary outcomes (13)
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.
Measured: Day 2 (In-Person Session)
Carotid Artery Stiffness
Functional assessment of the carotid artery stiffness will be assessed using B-mode ultrasound and artery edge-tracking software
Measured: 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
Measured: Day 2 (In-Person Session)
Arterial Stiffness
Measured by Pulse Wave Velocity (PWV) of the arm and leg
Measured: 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%.
Measured: 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.
Measured: 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).
Measured: 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).
Measured: Day 2 (In-Person Session)
Brain derived neurotrophic factor
Brain derived neurotrophic factor will be assessed via fasted venipuncture using in-house assays.
Measured: Day 2 (In-Person Session)
Lipid profile
HDL, LDL, total Cholesterol, Triglycerides analyzed from blood serum using a clinical assay at a core lab.
Measured: Day 2 (In-Person Session)
Hemoglobin A1c
Analyzed from blood plasma using a clinical assay at a core lab.
Measured: 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.
Measured: Day 2 (In-Person Session)
Protein metabolism
Analyzed from breathing test and urine sample before and after the participant consume a test protein drink.
Measured: Day 1 (At-Home Session)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2025
- Study start1 Feb 2025 (estimated)
- Primary completion30 Sep 2026 (estimated)
- Study completion30 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast Cancer FemalesStudies of the same condition, open and under way.
- More trials run by University of TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 112 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Cancer Research Society
- Responsible party
- Principal investigator, Amy Kirkham, University of Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06776458
- Sponsor's protocol ID
- REB #46819
- Acronym
- STRIVE-Chronic
- Status last verified
- Jan 2025
- First submitted
- 30 Dec 2024
- Last updated
- 15 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Beyond Cardiotoxicity: Characterizing the Long-term Cardiovascular Side Effects of Breast Cancer Endocrine Treatment
- ClinicalTrials.gov ID
- NCT06776458
- Acronym / sponsor ID
- STRIVE-Chronic / REB #46819
- Conditions
- Breast Cancer Females
- Keywords
- Aromatase Inhibitors, Breast Cancer Females, Heart Disease Risk Factors
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 112 participants (estimated)
- Lead sponsor
- University of TorontoUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Cancer Research Society
- Study start
- 1 Feb 2025 (estimated)
- Primary completion
- 30 Sep 2026 (estimated)
- Study completion
- 30 Sep 2026 (estimated)
- First posted
- 15 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
- 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.
- To examine the effects of aromatase inhibitor therapy on body composition, bone mineral density, and protein metabolism, in breast cancer survivors compared to controls.
- 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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Aromatase Inhibitors (1 year) | – | Other: N/A - Usual CareBreast cancer patients at 1-year post-diagnosis, who were treated with aromatase inhibitors |
| Aromatase Inhibitors (5 year) | – | Other: N/A - Usual CareBreast cancer patients at 5-year post-diagnosis, who were treated with aromatase inhibitors |
| Aromatase Inhibitors (10 years) | – | Other: N/A - Usual CareBreast 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) |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Participants will be recruited from the community in the Greater Toronto Area via posters, newsletters, social media advertisements, and word of mouth.
Key inclusion criteria (14 listed)
- 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
Key exclusion criteria (6 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| N/A - Usual CareBreast cancer survivors will have received usual care aromatase inhibitors for up to 10 years post-diagnosis. | Other | Aromatase Inhibitors (1 year), Aromatase Inhibitors (10 years), Aromatase Inhibitors (5 year) |
Primary outcome
Aortic Stiffness
Time frame: Day 2 (In-Person Session)
Aortic stiffness, measured non-invasively by pulse wave velocity, will be assessed using applanation tonometry.
13 secondary outcomes
Brachial Artery Endothelial Function
Time frame: Day 2 (In-Person Session)
Carotid Artery Stiffness
Time frame: Day 2 (In-Person Session)
Carotid Intima Media Thickness
Time frame: Day 2 (In-Person Session)
Arterial Stiffness
Time frame: Day 2 (In-Person Session)
Left Ventricular Ejection Fraction (LVEF)
Time frame: Day 2 (In-Person Session)
Global Longitudinal Strain
Time frame: Day 2 (In-Person Session)
Left Ventricular Diastolic Function
Time frame: Day 2 (In-Person Session)
Cerebrovascular Response
Time frame: Day 2 (In-Person Session)
Brain derived neurotrophic factor
Time frame: Day 2 (In-Person Session)
Lipid profile
Time frame: Day 2 (In-Person Session)
Hemoglobin A1c
Time frame: Day 2 (In-Person Session)
Insulin resistance
Time frame: Day 2 (In-Person Session)
Protein metabolism
Time frame: Day 1 (At-Home Session)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Breast Cancer Females, run by University of Toronto at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Amy A. Kirkham, PhD (416-946-4069, amy.kirkham@utoronto.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Aortic Stiffness (time frame: Day 2 (In-Person Session)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jan 2025.