Older Breast Cancer Patients: Risk for Cognitive Decline (TLC)

March 9, 2023 updated by: Jeanne Mandelblatt, Georgetown University

Older Breast Cancer Patients: Risk for Cognitive Decline. The Thinking and Living With Cancer (TLC) Study

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.

Study Overview

Status

Recruiting

Conditions

Detailed Description

Cancer is the leading cause of death in the US and breast cancer is the second most common cancer among women in our country. Older women (women 60 and older) presently account for nearly half of all new cases of breast cancer. With the "graying of America" and advances in treatment for breast cancer, the absolute number of older women undergoing breast cancer treatment and surviving their disease will almost double by the year 2030. Systemic hormonal and non-hormonal chemotherapy is credited with improvements in survival, and rates of use of these modalities have increased substantially over the past two decades. Preliminary work has found that older women are interested in chemotherapy even for small returns in survival extension. However, cognitive impairment has been demonstrated in most studies of breast cancer systemic treatments, but virtually all of this research has been conducted in younger populations. Since aging itself is associated with cognitive declines, it seems very likely that older women are particularly vulnerable to the adverse cognitive effects of systemic therapy; our preliminary work strongly suggests that this is the case, but this has never been empirically tested.

This study will be the first large-scale, prospective, controlled investigation to evaluate cognitive changes in older cancer patients and it will provide the basis for the next generation of mechanistic, treatment and intervention studies. These will be important since data from younger patients cannot be directly translated into the older population. Investigators will use the vulnerability model of cancer survivorship to prospectively describe the magnitude of systemic therapy effects on cognition in older (age >60 years) breast cancer patients over a 60 month period, explore change in APE, LM and Cognition domains, test associations between cognition and quality of life (QOL), and evaluate whether genetic polymorphisms, inflammatory biomarkers, sleep and physical measures moderate cognitive outcomes.

To achieve these objectives, investigators have assembled a multi-disciplinary team of oncologists, geriatricians, neurologists, neuro- and cognitive psychologists, behavioral scientists and consumers from Lombardi Comprehensive Cancer Center (LCCC), Memorial Sloan-Kettering Cancer Center (MSKCC), Moffitt Cancer Center, City of Hope National Medical Center (COH), Hackensack University Medical Center (HUMC), Indiana University (IU), Boston University (BU), University of California (UCLA), University of South Florida (USF) and their satellites, will work together to prospectively enroll 850 newly diagnosed older breast cancer cases from LCCC, MSKCC, Moffitt, COH, HUMC, IU and tertiary referral centers with high volumes. An equal number of non-cancer friend controls will be recruited. Friend controls were chosen since they will be similar to patients in most ways except for exposure to cancer and its treatments and they should be motivated to participate. If friends are not available, controls matched to cases on age, education, race, and area (DC/NY/FL/CA/NJ/IU) will be recruited from the community.

Investigators will administer baseline neuropsychological testing prior to any systemic treatment (or at enrollment for controls), survey women about subjective cognitive function, sleep, psychosocial factors, QOL and activities of daily living (IADLS). Subjects will take part in physical measurements, including grip strength, sit to stand and walk speed tests. Investigators will abstract clinical data from medical records. Investigators will obtain blood or saliva to test for APOE, COMT and other genetic polymorphisms at enrollment; these results will not be provided to participants since this is considered a research test). Subjects have the option to provide blood for biomarker research and for biobanking. Subjects will also provide one week of sleep monitoring. Subjects at IU will have the option to participate in neuroimaging. Investigators conduct follow-up interviews and repeat the neuropsychological testing, physical measures, blood/saliva collection, sleep monitoring and optional neuroimaging 12 months after baseline assessment; this time point corresponds to 3-6 months post-treatment among women who receive chemotherapy. Our primary cognitive outcome will be change in summary score on tests in the Attention, Processing Speed, and Executive Function domain, Learning and Memory domain, and Subjective Cognition domain. In secondary analyses, investigators examine changes in scores on additional domains to assess broader cognitive function and examine questions of differential impact.

Data from this study will guide future interventions to better select older women for whom the benefits of systemic therapy outweigh the harms and to develop approaches to mitigate negative consequences of systemic treatment when it is indicated, improving the quality of care for the growing population of older breast cancer patients.

Study Type

Observational

Enrollment (Anticipated)

1700

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Recruiting
        • Georgetown University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years to 105 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Sampling Method

Non-Probability Sample

Study Population

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

Description

Inclusion Criteria:

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.

Exclusion:

We apply the same exclusion criteria for patients and controls.

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Attention, Processing Speed, Executive Function (APE) Domain
Time Frame: Baseline and annually up to 5 years
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
Time Frame: Baseline and annually up to 5 years
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
Time Frame: Baseline and annually up to 5 years

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Quality of Life
Time Frame: Baseline and annually up to 5 years
Using Functional Assessment of Cancer Therapy-Breast quality of life measure (FACT-B)
Baseline and annually up to 5 years
Change in Quality of Life
Time Frame: Baseline and annually up to 5 years
Using Medical Outcome Study measure (MOS)
Baseline and annually up to 5 years
Change in Quality of Life
Time Frame: Baseline and annually up to 5 years
Using Short Form Health Survey measure (SF-12)
Baseline and annually up to 5 years
Change in cancer-related symptoms (including fatigue, sleep, pain, anxiety and depression)
Time Frame: Baseline and annually up to 5 years
Using survey data
Baseline and annually up to 5 years
Biomarkers of aging (genotype, inflammatory biomarkers, telomere length, p16, miRNA)
Time Frame: Baseline and annually up to 5 years
Using annual biospecimen collection of blood or saliva
Baseline and annually up to 5 years
Grip Strength Test
Time Frame: Baseline and annually up to 5 years
Participant's grip strength will be measured using the Jamar Plus Digital dynamometer. The participant should be in a standing position, arms at their side, not touching their body with elbow bent slightly. If subjects are unable to stand comfortably, they will be seated in a chair with their feet touching the ground with their elbow bent to 90 degrees and the arm against their trunk with a neutral wrist. Participants squeeze the Jamar Plus Digital dynamometer as hard as they can for a count of three. The dynamometer provides a digital reading of force in pounds. A practice trial at less than full force and one test trial are completed with each hand. The test takes approximately three minutes to administer. Dominant vs. Non-Dominant Hand (i.e., handedness) is assessed at the outset.
Baseline and annually up to 5 years
Actigraphy/Change in Sleep
Time Frame: Baseline and annually up to 5 years
To obtain an objective assessment of both daytime and nighttime sleeping, participants will wear the actigraph on the dominant wrist (unless that arm is paralyzed) for one week. The Actigraph Motionlogger (Ambulatory Monitoring, Inc. Ardsley, NY), is a wrist-mounted actigraph that records activity and illumination exposure using an accelerometer, a light transducer and a microprocessor. Commercially available software uses validated algorithms that take into account wrist movement immediately before and after an epoch of interest; wrist activity below an established threshold is interpreted as sleep and wrist activity above that threshold is interpreted as wakefulness as validated in older adults. Agreement between wrist actigraphy and EEG (the gold standard method for sleep assessment) scoring of sleep variables (e.g., total sleep time) is 89-95% in older adults.
Baseline and annually up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Georgetown University

Collaborators

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

Investigators

  • Principal Investigator: Jeanne Mandelblatt, Lombardi Comprehensive Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2010

Primary Completion (Anticipated)

December 31, 2023

Study Completion (Anticipated)

December 31, 2023

Study Registration Dates

First Submitted

January 29, 2018

First Submitted That Met QC Criteria

February 22, 2018

First Posted (Actual)

March 1, 2018

Study Record Updates

Last Update Posted (Actual)

March 13, 2023

Last Update Submitted That Met QC Criteria

March 9, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2008-363

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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