Brain Health in Breast Cancer Survivors

Study Overview
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Brief Summary
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Endocrine therapy (ET) is widely used to treat hormone receptor positive breast cancer and prevent recurrence by downregulating estrogen function. However, ETs readily cross the blood brain barrier and interfere with the action of estrogen in the brain. Estrogen supports cognition and menopausal status is closely linked to cognitive health in women. This has raised concern that anti-estrogen ETs may affect cognition and brain health in breast cancer survivors. However, evidence across existing studies is inconsistent and these effects remain poorly understood. The incomplete understanding of the effects of ET are likely due to limitations of earlier studies - namely, the under-appreciation of the role of menopausal status and insensitivity of standard cognitive measures. This research project will address these earlier limitations by specifically comparing ET effects by menopausal status, and using highly sensitive, task-related functional magnetic resonance imaging (fMRI) measures to assess the effects of ET on brain function.

Detailed Description
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Endocrine therapy (ET) is widely used to treat hormone receptor positive breast cancer and prevent recurrence by downregulating estrogen function. However, ETs readily cross the blood brain barrier and interfere with the action of estrogen in the brain. Estrogen supports cognition and menopausal status is closely linked to cognitive health in women. This has raised concern that anti-estrogen ETs may affect cognition and brain health in breast cancer survivors. However, evidence across existing studies is inconsistent and these effects remain poorly understood. The incomplete understanding of the effects of ET are likely due to limitations of earlier studies - namely, the under-appreciation of the role of menopausal status and insensitivity of standard cognitive measures. This research project will address these earlier limitations by specifically comparing ET effects by menopausal status, and using highly sensitive, task-related fMRI measures to assess the effects of ET on brain function. This study is a cross-sectional study in a 2x2 factorial design comparing menopausal status (pre and post) and patient group (breast cancer survivors on ET and healthy controls matched on age, race, education, and time since final menstrual period (post only)). The investigators will use sensitive fMRI measures of brain activity during a working memory task - measures successfully used to reveal the effects of menopause and estrogen changes in healthy women, but yet to be extensively used to study the effects of ET.

Official Title
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Brain Health in Breast Cancer Survivors: Interaction of Menopause and Endocrine Therapy

Conditions
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Cognitive Impairment, Cognitive Function

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 35-65 Fluent in English Adequate vision/hearing to complete testing Exclusion Criteria: History of major or mild neurocognitive disorder or dementia Diagnosis of major neurological condition (e.g., epilepsy, Parkinson's Disease, stroke) Diagnosis of a major psychiatric disorder (e.g., bipolar disorder, schizophrenia) Untreated/unstable unipolar depression or anxiety Prior history of cancer or chemotherapy (for controls, any history) History of a learning disorder History of head injury with loss of consciousness >20 minutes History of salpingo-oophorectomy or hysterectomy A cardiac pacemaker Implanted electronic device Claustrophobia Currently pregnant Orbital metal implant or other metallic foreign bodies Additional exclusion criteria for controls: current use of a contraceptive agent that interferes with endogenous hormonal fluctuation (e.g., oral contraceptive pill) or precludes determination of menstrual pattern (e.g., hormonally secreting intrauterine device), or current treatment with systemic estrogen replacement therapy.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pre-menopausal BCS + ET<br>Pre-menopausal Breast Cancer Survivor (BCS) who have undergone Endocrine Therapy (ET) | |
| Post-menopausal BCS + ET<br>Post-menopausal Breast Cancer Survivor (BCS) who have undergone Endocrine Therapy (ET) | |
| Pre-menopausal Healthy Control<br>Pre-menopausal healthy control group | |
| Post-menopausal Healthy Control<br>Post-menopausal healthy control group | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain activity comparison between breast cancer survivors undergoing endocrine therapy and healthy matched control subject. | To compare brain activity using fMRI during a working memory task between breast cancer survivors on ET and matched healthy controls, and examine the interaction of menopausal status. | Day 1 | 
| Cognitive function comparison between breast cancer survivors undergoing endocrine therapy and healthy matched control subject. | To compare cognitive function between breast cancer survivors on ET and matched healthy controls, and examine the interaction of menopausal status. | Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast cancer, endocrine therapy