Brain Health in Breast Cancer Survivors

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

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.

Study Overview

• Status: Recruiting
• Conditions: Cognitive Impairment; Cognitive Function

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

• Study Contact: Name: Kathleen Van Dyk, PhD; Phone Number: 310 825-2719; Email: KVanDyk@mednet.ucla.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • University of California at Los Angeles
      • Contact: Kathleen Van Dyk; Phone Number: 310-825-2719; Email: kvandyk@mednet.ucla.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

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).

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Pre-menopausal BCS + ET; Pre-menopausal Breast Cancer Survivor (BCS) who have undergone Endocrine Therapy (ET)
Post-menopausal BCS + ET; Post-menopausal Breast Cancer Survivor (BCS) who have undergone Endocrine Therapy (ET)
Pre-menopausal Healthy Control; Pre-menopausal healthy control group
Post-menopausal Healthy Control; Post-menopausal healthy control group

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Jonsson Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Kathleen Van Dyk, PhD, University of California at Los Angeles

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2020
• Primary Completion (Estimated): March 15, 2025
• Study Completion (Estimated): March 15, 2026

Study Registration Dates

• First Submitted: February 28, 2020
• First Submitted That Met QC Criteria: March 4, 2020
• First Posted (Actual): March 5, 2020

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Breast cancer; endocrine therapy
• Additional Relevant MeSH Terms: Mental Disorders; Skin Diseases; Neoplasms; Neoplasms by Site; Neurocognitive Disorders; Breast Diseases; Cognition Disorders; Breast Neoplasms; Cognitive Dysfunction
• Other Study ID Numbers: 19-001004; K08CA241337 (U.S. NIH Grant/Contract); NCI-2020-01501 (Registry Identifier: CTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No