Exercise and Cognitive (Brain) Function in Breast Cancer Patients Getting Chemotherapy After Breast Surgery

Cardiorespiratory Fitness, Inflammatory Biomarkers, and Cognitive Function Patterns During Treatment for Breast Cancer: A Prospective Cohort Study

This study will primarily identify longitudinal associations between cardiorespiratory fitness (CRF) and cognitive function pre- (baseline) to post-chemotherapy (~3 months). This will be a prospective study of 50 BCS. We hypothesize that breast cancer patients undergoing chemotherapy who have higher levels of CRF at baseline will have significantly improved measures of attention, executive function, and memory post-chemotherapy. In addition, the exploratory aims will examine the longitudinal associations between physical activity (PA) and cognitive function from pre- to post-chemotherapy and explore the associations between inflammatory and non-inflammatory biomarkers and CRF with cognitive function.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer

Detailed Description

Detailed Description:

Cognitive impairments are reported as a chief quality of life (QoL) complaint by approximately 75% of breast cancer survivors (BCS). Women who have undergone adjuvant chemotherapy are at the highest risk for cognitive impairments, that may affect BCS up to 20 years post-treatment.Despite the prevalence and significance, it is largely underdiagnosed and there are no proven treatments beyond symptom management. Several studies have assessed cognitive function in cancer populations. Increasing evidence highlights the role of lifestyle behaviours on cancer-related outcomes, ranging from QoL to prognosis. However, very few studies have examined the associations of lifestyle factors and cognitive function in BCS.One of the most important mediators of CRCI in BCS may be cardiorespiratory fitness (CRF).

Our overall objective is to examine the behavioral and biological mechanisms that contribute to cognitive decline in BCS undergoing chemotherapy using an epidemiologic, prospective cohort design.

Assessments taken at baseline (pre-chemotherapy) and post-chemotherapy (month 3). Cognitive Function will be assessed using the NIH toolbox cognition battery. Physical Activity. PA will be assessed by accelerometers and through self-report using the Godin-Leisure Time Exercise Questionnaire. Cardiorespiratory Fitness will be assessed using the 6-minute walk test to estimate maximum oxygen uptake (VO2max).Cancer Biomarkers will be assessed using venous blood (2 microtubes) will be drawn from the antecubital vein by a trained phlebotomist. Biological markers analyzed in blood will include a multiplex panel of inflammatory cytokines (i.e., IL1, IL6, TNFα), and brain-derived neurotrophic factor (BDNF).

Our proposed study will be instrumental in designing future targeted translational lifestyle interventions to improve cognitive health in BCS. In addition, understanding the trajectory of cognitive function as it relates to these factors will determine the opportune timeframe to intervene during the cancer care continuum for the greatest impact.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Linda Trinh, PhD; Phone Number: (416) 946-3624; Email: linda.trinh@utoronto.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N3M5
      • Recruiting
      • Sunnybrook Health Sciences Centre-Odette Cancer Centre
      • Contact: Ellen Warner, MD
      • Principal Investigator: Ellen Warner, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

50 BCS from the Odette Cancer Centre and breast cancer organizations within the Greater Toronto Area

Description

Inclusion Criteria:

• 18-65 years old
• histologically-confirmed stage I-III breast cancer, but prior to the initiation of chemotherapy (<1 cycle of adjuvant therapy or neoadjuvant therapy)
• no diagnosed major cognitive disorders and uncontrolled comorbidities.

Exclusion Criteria:

• received neoadjuvant chemotherapy and scheduled to receive adjuvant chemotherapy
• scheduled to receive concurrent radiation therapy with chemotherapy.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fluid Cognition (Composite)	Cognitive function will be assessed using the NIH toolbox cognition battery. The NIH toolbox cognition battery with computerized cognitive tasks and automated scoring was used (Weintraub et al., 2013). This composite includes all the tests noted above that are fluid ability measures: Flanker, Dimensional Change Card Sort, Picture Sequence Memory, List Sorting and Pattern Comparison. This composite score is derived by averaging the normalized scores of each of the measures, and then deriving scale scores based on this new distribution. An Age-Adjusted Scale Score, Fully Adjusted Scale Score, Unadjusted Scale Score and Age-Adjusted National Percentile are provided for the Fluid Cognition Composite. The Fluid Cognition Composite is a more global assessment of individual and group fluid cognition functioning. Higher scores indicate higher levels of functioning.	Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Executive/Attention	Cognitive function will be assessed using the NIH toolbox cognition battery. The NIH toolbox cognition battery with computerized cognitive tasks and automated scoring was used (Weintraub et al., 2013). The Flanker Inhibitory Control and Attention Test tests the ability to inhibit visual attention to irrelevant task dimensions. A scoring algorithm integrates accuracy and reaction time yielding scores from 0 to 10. There are 40 trials and the average time to complete the task is 4 minutes.To interpret individual performance, one can evaluate all three types of scale scores in which higher scores indicate higher levels of ability to attend to relevant stimuli and inhibit attention from irrelevant stimuli.	Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).
Executive/Shifting	Cognitive function will be assessed using the NIH toolbox cognition battery. The NIH toolbox cognition battery with computerized cognitive tasks and automated scoring was used (Weintraub et al., 2013). The Dimensional Change Card Sort Test involves a target visual stimulus that must be matched to 1 of 2 choice stimuli according to shape or color. Scoring is based on an algorithm that weights reaction time. A total of 40 trials require 4 minutes. Higher scores indicate higher levels of cognitive flexibility.	Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).
Working Memory	The NIH toolbox cognition battery with computerized cognitive tasks and automated scoring was used (Weintraub et al., 2013). The List Sorting Working Memory Test includes a series of stimuli is presented on the computer screen visually (object) and orally (spoken name), 1 at a time. Participants are instructed to repeat the stimuli to the tester in order of size, from smallest to largest. The List Sorting task takes approximately 7 minutes to administer. Test scores consist of total items correct across all trials. Higher scores indicate better working memory.The NIH toolbox cognition battery with computerized cognitive tasks and automated scoring was used (Weintraub et al., 2013). The Picture Vocabulary Test involves single words that are presented via an audio file, paired simultaneously with 4 screen images of objects, actions, and/or depictions of concepts. The participant will pick the picture that match	Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).
Episodic Memory	Cognitive function will be assessed using the NIH toolbox cognition battery. The NIH toolbox cognition battery with computerized cognitive tasks and automated scoring was used (Weintraub et al., 2013). The Picture Sequence Memory Test involves a presentation of stimuli which are pictured objects and activities, thematically related but with no inherent order. For each trial, pictures appear in the center of the screen and then are moved 1 at a time into a fixed spatial order, as an audio file simultaneously describes the content of each. The score is based on the cumulative number of adjacent pairs of pictures remembered correctly over 3 learning trials. The test takes approximately 10 minutes. Higher scores indicate better episodic memory.	Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).
Language (oral reading)	Cognitive function will be assessed using the NIH toolbox cognition battery. The NIH toolbox cognition battery with computerized cognitive tasks and automated scoring was used (Weintraub et al., 2013). The Oral Reading Recognition Test measures the ability to pronounce single printed words and/or to recognize letters. Items are administered by computer adaptive testing (CAT) and participant responses are entered by the tester. The CAT item bank contains approximately 250 items with only 30 to 40 that will be presented, depending on performance. Average administration time is 4 minutes. A higher Computed Score for Reading would mean that the participant is able to correctly identify more difficult words on the subsequent assessment, which may indicate developmental growth or a return to a previous level of functioning.	Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).
Language (picture vocabulary)	Cognitive function will be assessed using the NIH toolbox cognition battery. The NIH toolbox cognition battery with computerized cognitive tasks and automated scoring was used (Weintraub et al., 2013). The Picture Vocabulary Test involves single words that are presented via an audio file, paired simultaneously with 4 screen images of objects, actions, and/or depictions of concepts. The participant will pick the picture that matches the spoken word. Total administration time is approximately 5 minutes. To interpret individual performance, one can evaluate all three types of scale scores. A participant's age-adjusted scale score at or near 100 indicates vocabulary ability that is average for the age level. Scores around 115 suggest above-average vocabulary ability, while scores around 130 suggest superior ability - in the top 2 percent nationally for age, based on Toolbox normative data.	Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).
Processing Speed (Pattern comparison)	Cognitive function will be assessed using the NIH toolbox cognition battery. The NIH toolbox cognition battery with computerized cognitive tasks and automated scoring was used (Weintraub et al., 2013). The Pattern Comparison Processing Speed Test requires participants to identify whether two visual patterns are the "same" or "not the same." Average time of administration is 3 minutes and the score is the number of correct items (of a possible 130) completed in 90 seconds. Higher scores indicate faster speed of processing.	Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).
Crystallized Cognition	Cognitive function will be assessed using the NIH toolbox cognition battery. The NIH toolbox cognition battery with computerized cognitive tasks and automated scoring was used (Weintraub et al., 2013). This composite includes the Picture Vocabulary and Reading Tests. This composite score is derived by averaging the normalized scores of each of the measures, and then deriving scale scores based on this 14 new distribution. An Age-Adjusted Scale Score, Fully Adjusted Scale Score, Unadjusted Scale Score and Age-Adjusted National Percentile are provided for the Crystallized Cognition Composite. Crystallized Cognition Composite is a more global assessment of individual and group verbal reasoning. Higher scores indicate higher levels of functioning.	Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).
Immediate Recall	Cognitive function will be assessed using the NIH toolbox cognition battery. The NIH toolbox cognition battery with computerized cognitive tasks and automated scoring was used (Weintraub et al., 2013). The Auditory Verbal Learning Test (Rey) measures immediate recall. Unrelated words presented via audio recording and participant recalls as many as possible. he Rey is scored by taking the sum of the number of words recalled across all trials (possible range is 0-45 words). The raw score is most commonly used for interpretation of the Rey test, with higher scores reflecting better episodic memory.	Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).
Processing Speed (oral symbol digit test)	Cognitive function will be assessed using the NIH toolbox cognition battery. The NIH toolbox cognition battery with computerized cognitive tasks and automated scoring was used (Weintraub et al., 2013). The Oral Symbol Digit Test measures speed of processing. Symbols on the screen are associated with a number, then presented with symbols without numbers. The Oral Symbol Digit Test is scored as the number of items answered correctly in 120 seconds (possible range is 0-144).Higher scores indicate better processing speed.	Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).
Objectively-assessed physical activity	Objectively assessed PA was measured using Actigraph GTX3+ accelerometers (Pensacola, FL). Participants will wear the accelerometer on their non-dominant hip during waking hours for 7 consecutive days. Data will be downloaded in 60-s epochs and processed and converted to mean counts per minute in ActiLife software package (Version 6; Actigraph) to estimate daily minutes of light (101-1951 counts min-1), moderate (1952-5724 counts min-1), vigorous (≥ 5725 counts min-1), and total moderate-to-vigorous physical activity (MVPA; ≥ 1952 counts min-1) based on established cut-points (Freedson, Melanson, & Sirard, 1998). Estimated average daily minutes spent in each activity intensity category was calculated by dividing the number of minutes spent in each category by the total number of valid days worn.	Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).
Self-reported physical activity	Physical activity will be assessed using a modified version of the validated leisure score index (LSI) from the Godin Leisure-Time Exercise Questionnaire (GLTEQ). Participants are asked to recall the average number of times per week and average duration they performed light (minimal effort, no perspiration), moderate (not exhausting, light perspiration), and vigorous (heart beats rapidly, sweating) physical activity during free time in the past month. The percentage of participants meeting the public health aerobic physical activity guidelines was calculated based on the physical activity guidelines recommended for cancer survivors by the American College of Sports Medicine. These guidelines recommend that individuals obtain 75 min of vigorous aerobic physical activity per week, 150 min of moderate aerobic physical activity per week, or an equivalent combination. Thus, will calculated physical activity minutes as moderate minutes plus two times the vigorous minutes.	Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).
Cancer biomarkers	Cancer Biomarkers will be assessed using venous blood (2 microtubes) will be drawn from the antecubital vein by a trained phlebotomist. Biological markers analyzed in blood will include a multiplex panel of inflammatory cytokines (i.e., IL1, IL6, TNFα), and brain-derived neurotrophic factor (BDNF).	Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).
Cardiorespiratory fitness	Cardiorespiratory Fitness will be assessed using the six-minute walk test (6MWT) to estimate maximum oxygen uptake (VO2max).The 6MWT measures the distance in meters an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes at their own pace.A lower score (reflecting less distance covered) indicates worse function.	Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).

Collaborators and Investigators

• Sponsor: University of Toronto

Publications and helpful links

General Publications

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Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2019
• Primary Completion (Estimated): April 30, 2024
• Study Completion (Estimated): April 30, 2024

Study Registration Dates

• First Submitted: November 2, 2020
• First Submitted That Met QC Criteria: November 2, 2020
• First Posted (Actual): November 4, 2020

Study Record Updates

• Last Update Posted (Actual): November 28, 2023
• Last Update Submitted That Met QC Criteria: November 27, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: physical activity; cognitive function; cardiorespiratory fitness; chemotherapy treatment; cancer biomarkers
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 38406

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