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

Official title

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

Overview

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.

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.

Primary outcome measures

• Fluid Cognition (Composite) [Time frame: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).]

Secondary outcome measures (12)

• Executive/Attention [Time frame: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).]
• Executive/Shifting [Time frame: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).]
• Working Memory [Time frame: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).]
• Episodic Memory [Time frame: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).]
• Language (oral reading) [Time frame: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).]
• Language (picture vocabulary) [Time frame: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).]
• Processing Speed (Pattern comparison) [Time frame: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).]
• Crystallized Cognition [Time frame: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).]
• Immediate Recall [Time frame: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).]
• Processing Speed (oral symbol digit test) [Time frame: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).]
• Objectively-assessed physical activity [Time frame: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).]
• Self-reported physical activity [Time frame: Change in from baseline (pre-chemotherapy) and post-chemotherapy (month 3).]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Canada · 1 center

• Sunnybrook Health Sciences Centre-Odette Cancer Centre — Toronto

Publications

• Castellon SA, Ganz PA, Bower JE, Petersen L, Abraham L, Greendale GA. Neurocognitive performance in breast cancer survivors exposed to adjuvant chemotherapy and tamoxifen. J Clin Exp Neuropsychol. 2004 Oct;26(7):955-69. doi: 10.1080/13803390490510905. PMID 15742545
• Kesler SR, Kent JS, O'Hara R. Prefrontal cortex and executive function impairments in primary breast cancer. Arch Neurol. 2011 Nov;68(11):1447-53. doi: 10.1001/archneurol.2011.245. PMID 22084128
• Koppelmans V, Breteler MM, Boogerd W, Seynaeve C, Gundy C, Schagen SB. Neuropsychological performance in survivors of breast cancer more than 20 years after adjuvant chemotherapy. J Clin Oncol. 2012 Apr 1;30(10):1080-6. doi: 10.1200/JCO.2011.37.0189. Epub 2012 Feb 27. PMID 22370315
• Kesler S, Hadi Hosseini SM, Heckler C, Janelsins M, Palesh O, Mustian K, Morrow G. Cognitive training for improving executive function in chemotherapy-treated breast cancer survivors. Clin Breast Cancer. 2013 Aug;13(4):299-306. doi: 10.1016/j.clbc.2013.02.004. Epub 2013 May 4. PMID 23647804
• Von Ah D, Tallman EF. Perceived cognitive function in breast cancer survivors: evaluating relationships with objective cognitive performance and other symptoms using the functional assessment of cancer therapy-cognitive function instrument. J Pain Symptom Manage. 2015 Apr;49(4):697-706. doi: 10.1016/j.jpainsymman.2014.08.012. Epub 2014 Sep 18. PMID 25240787
• Frank JS, Vance DE, Triebel KL, Meneses KM. Cognitive Deficits in Breast Cancer Survivors After Chemotherapy and Hormonal Therapy. J Neurosci Nurs. 2015 Dec;47(6):302-12. doi: 10.1097/JNN.0000000000000171. PMID 26447567
• Von Ah D, Habermann B, Carpenter JS, Schneider BL. Impact of perceived cognitive impairment in breast cancer survivors. Eur J Oncol Nurs. 2013 Apr;17(2):236-41. doi: 10.1016/j.ejon.2012.06.002. Epub 2012 Aug 14. PMID 22901546
• Argyriou AA, Assimakopoulos K, Iconomou G, Giannakopoulou F, Kalofonos HP. Either called "chemobrain" or "chemofog," the long-term chemotherapy-induced cognitive decline in cancer survivors is real. J Pain Symptom Manage. 2011 Jan;41(1):126-39. doi: 10.1016/j.jpainsymman.2010.04.021. Epub 2010 Sep 15. PMID 20832978

Identifiers

NCT: NCT04616300 · 38406

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗