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.

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.

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.

Pre-menopausal and post-menopausal breast cancer survivors who are undergoing endocrine therapy.

Pre-menopausal and post-menopausal breast cancer survivors who are undergoing endocrine therapy will be compared to healthy control group matched by age, race, education and time since final menstrual period (post only).