Older Breast Cancer Patients: Risk for Cognitive Decline

NCT03451383 | Recruiting

• 1 other identifier: 2008-363
• Study Type: observational
• Target: 1,700
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to evaluate the impact of systemic therapy on cognition in older breast cancer patients, explore change in APE, LM and Cognition domains, measure associations between cognitive decline and QOL, and describe how genetic polymorphisms, inflammatory biomarkers, sleep and physical measures moderate cognitive outcomes. This study is being done nationally, with recruiting sites at Georgetown University, Montgomery General Hospital, Virginia Cancer Specialists, Washington Hospital Center, Reston Breast Care Specialists, Memorial Sloan-Kettering, Moffitt Cancer Center, City of Hope National Medical Center, Hackensack University Medical Center, Indiana University and University of California, Los Angeles.

Conditions

Cancer, Breast; Age-related Cognitive Decline; Cognitive Decline

Keywords

breast cancer; cognitive decline

Outcome Measures

Primary Outcomes (3)

• Change in Attention, Processing Speed, Executive Function (APE) Domain

  Using neuropsychological tests: NAB Digits Forward and Backward, Trailmaking A and B, Digit Symbol Subtest-Wechsler Adult, The Timed Instrumental Activities of Daily Living, Controlled Oral Word Association Test, NAB Driving Scenes and NAB Figure Drawing. These measures are aggregated to arrive at one reported value. The individual tests are first selected via factor analysis, then the selected raw scores are standardized to baseline controls by age and education group. The final domain score is calculated by averaging available individual z-standardized test scores.

  Baseline and annually up to 5 years

• Change in Learning and Memory (LM) Domain

  Using neuropsychological tests: Logical Memory I and II (Wechsler Memory Scale), NAB List Learning (Immediate Recall, Short Delay Recall, Long Delay). These measures are aggregated to arrive at one reported value. The individual tests are first selected via factor analysis, then the selected raw scores are standardized to baseline controls by age and education group. The final domain score is calculated by averaging available individual z-standardized test scores.

  Baseline and annually up to 5 years

• Change in Cognition Domain

  Using assessment: FACT-Cog and PCI Sub-scale. The measures are aggregated to arrive at one reported value. Change in cognition is calculated based on the official FACT-Cog scoring manual. The total score is calculated by summing the available items among all 37 items when no more than 30 items are missing. The PCI subscale score is calculated by summing the available items among all 18 items when no more than 8 items are missing.

  Baseline and annually up to 5 years

Secondary Outcomes (7)

• Change in Quality of Life

  Baseline and annually up to 5 years

• Change in Quality of Life

  Baseline and annually up to 5 years

• Change in Quality of Life

  Baseline and annually up to 5 years

• Change in cancer-related symptoms (including fatigue, sleep, pain, anxiety and depression)

  Baseline and annually up to 5 years

• Biomarkers of aging (genotype, inflammatory biomarkers, telomere length, p16, miRNA)

  Baseline and annually up to 5 years

Study Arms (2)

Breast Cancer Case

Women age 60+ with a newly diagnosed breast adenocarcinoma staged 0-3.

Non-Cancer Controls

Women age 60+ with no diagnosis of breast cancer.

Eligibility Criteria

• Age: 60 Years - 105 Years
• Gender Eligibility Details: Female breast cancer cases and female matched non-cancer controls
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Women age 60+ with a newly diagnosed breast adenocarcinoma staged 0-3 and matched controls.

You may qualify if:

• For cancer patients, eligibility includes:
• being female
• Age 60+ at diagnosis of a new primary histological confirmed adenocarcinoma breast cancer
• AJCC stages 0-3 or planning neoadjuvant therapy
• In the judgment of the consenting professional, able to communicate well enough in English through verbal and written communication to complete the study assessments and provide informed consent
• If currently taking psychoactive medications (including, but not limited to anticonvulsants, antidepressants, and anxiolytics), dose must have been stable at least two months prior to enrollment.
• Participant report of no previous or current chemotherapy or hormonal treatment use (anastrazole, exemestane, etc.) This does not include hormonal replacement therapy, synthetic thyroid hormones, etc.
• For controls, eligibility includes:
• being female
• Age 60+
• In the judgment of the consenting professional, able to communicate well enough in English through verbal and written communication to complete the study assessments and provide informed consent
• If currently taking psychoactive medications (including, but not limited to anticonvulsants, antidepressants, and anxiolytics), dose must have been stable at least two months prior to enrollment.

You may not qualify if:

• Participant report of a history of formal diagnosis of neurological problems (i.e. Alzheimer's disease, Parkinson's disease, Multiple Sclerosis, Dementia, Seizure Disorders, brain tumors, etc.)
• Participant report of surgery on the brain for any reason (cancerous or non-cancerous tumors, subdural hematomas, AV malformations, increased intracranial pressure, etc.)
• Participant report of a history of stroke (with the exception of TIA if ≥1 year ago)
• Participant report of HIV/AIDS
• Participant report of moderate to severe head trauma (loss of consciousness \> 60 min or with evidence of structural brain changes on imaging)
• History of major psychiatric disorder (DSM-IV Axis 1) (i.e. major depressive disorder (untreated or poorly treated), bipolar disorders, schizophrenia, or substance abuse disorders (self-reported and/or stated in medical record).
• Participant report of a history of prior breast or other cancer with the exception of non-melanoma skin cancer. An exception for cases only: women who completed treatment for a previous cancer at least 5 years ago and have not undergone any chemotherapy or hormonal therapy. This previous cancer cannot be breast cancer.
• Participant report of previous or current chemotherapy or hormonal therapy use
• Participant use of methotrexate (Amethopterin, Rhematrex, Trexall) or rituximab (Rituxin) for rheumatoid arthritis, psoriasis or Crohn's disease, or cyclophosphamide (Cytoxan, Neosar) for Lupus.
• Visual or hearing impairment that would preclude ability to complete interviews or neuropsychological testing, such as significant macular degeneration or being unable to correct hearing with hearing aides
• Non-English speaking
• To participate in the optional neuroimaging portion of the study:
• Participant cannot be claustrophobic Participant cannot have a pacemaker, aneurysm clip or other implants that are not MRI safe Participant cannot have any type of implanted electrical device

Sponsors & Collaborators

• Georgetown University: lead
• Memorial Sloan Kettering Cancer Center: collaborator
• Indiana University: collaborator
• H. Lee Moffitt Cancer Center and Research Institute: collaborator
• City of Hope Medical Center: collaborator
• Hackensack Meridian Health: collaborator

Study Sites (1)

Georgetown University

Washington D.C., District of Columbia, 20007, United States

RECRUITING

Related Publications (5)

• McDonald BC, Van Dyk K, Deardorff RL, Bailey JN, Zhai W, Carroll JE, Root JC, Ahles TA, Mandelblatt JS, Saykin AJ. Multimodal MRI examination of structural and functional brain changes in older women with breast cancer in the first year of antiestrogen hormonal therapy. Breast Cancer Res Treat. 2022 Jul;194(1):113-126. doi: 10.1007/s10549-022-06597-1. Epub 2022 Apr 27.

  PMID: 35476252 DERIVED

• Bethea TN, Zhai W, Zhou X, Ahles TA, Ahn J, Cohen HJ, Dilawari AA, Graham DMA, Jim HSL, McDonald BC, Nakamura ZM, Patel SK, Rentscher KE, Root J, Saykin AJ, Small BJ, Van Dyk KM, Mandelblatt JS, Carroll JE. Associations between longitudinal changes in sleep disturbance and depressive and anxiety symptoms during the COVID-19 virus pandemic among older women with and without breast cancer in the thinking and living with breast cancer study. Cancer Med. 2022 Sep;11(17):3352-3363. doi: 10.1002/cam4.4682. Epub 2022 Mar 22.

  PMID: 35315588 DERIVED

• Dilawari A, Rentscher KE, Zhai W, Zhou X, Ahles TA, Ahn J, Bethea TN, Carroll JE, Cohen HJ, Graham DA, Jim HSL, McDonald B, Nakamura ZM, Patel SK, Root JC, Small BJ, Saykin AJ, Tometich D, Van Dyk K, Mandelblatt JS; Thinking and Living with Cancer Study. Medical care disruptions during the first six months of the COVID-19 pandemic: the experience of older breast cancer survivors. Breast Cancer Res Treat. 2021 Nov;190(2):287-293. doi: 10.1007/s10549-021-06362-w. Epub 2021 Sep 13.

  PMID: 34515905 DERIVED

• Carroll JE, Small BJ, Tometich DB, Zhai W, Zhou X, Luta G, Ahles TA, Saykin AJ, Nudelman KNH, Clapp JD, Jim HS, Jacobsen PB, Hurria A, Graham D, McDonald BC, Denduluri N, Extermann M, Isaacs C, Dilawari AA, Root J, Stern RA, Mandelblatt JS; Thinking and Living With Cancer Study. Sleep disturbance and neurocognitive outcomes in older patients with breast cancer: Interaction with genotype. Cancer. 2019 Dec 15;125(24):4516-4524. doi: 10.1002/cncr.32489. Epub 2019 Sep 25.

  PMID: 31553501 DERIVED

• Tometich DB, Small BJ, Carroll JE, Zhai W, Luta G, Zhou X, Kobayashi LC, Ahles T, Saykin AJ, Clapp JD, Jim HSL, Jacobsen PB, Hurria A, Graham D, McDonald BC, Denduluri N, Extermann M, Isaacs C, Dilawari A, Root J, Rini C, Mandelblatt JS; Thinking and Living with Cancer (TLC) Study. Pretreatment Psychoneurological Symptoms and Their Association With Longitudinal Cognitive Function and Quality of Life in Older Breast Cancer Survivors. J Pain Symptom Manage. 2019 Mar;57(3):596-606. doi: 10.1016/j.jpainsymman.2018.11.015. Epub 2018 Nov 23.

  PMID: 30472317 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

A total of up to 27ml of blood will be collected at each time point for APOE and COMT DNA testing, inflammatory biomarkers, plasma AD-pathology markers (Aβ1- 42, tau, p-tau, and neurofilament light chain \[NFL\]), the receptor for advanced glycation end- products (RAGE) and danger-associated molecular patterns (DAMPs: Aβ, S100 proteins, and HMBG1) and for storage of DNA and RNA for future research. If the subject is unable to provide a blood sample at their visit, 2ml of saliva will be collected using Oragene DNA Collection kits.

MeSH Terms

Conditions

Breast Neoplasms; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Jeanne Mandelblatt

  Lombardi Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jeanne Mandelblatt

CONTACT

2026870801; mandelbj@georgetown.edu

Meghan Mihalache

CONTACT

2026878247; mem323@georgetown.edu

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 29, 2018
• First Posted: March 1, 2018
• Study Start: August 1, 2010
• Primary Completion: April 30, 2025
• Study Completion: April 30, 2025
• Last Updated: March 11, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)