Chemotherapy Effect on Brain Structure, Neurophysiology and Psychomotor Behavior in Breast Cancer Patients

Some cancer patients report experiencing mild problems with thinking during or following chemotherapy. Symptoms include problems concentrating, slow thinking, some gaps in memory and difficulty performing complex or multi-tasks. These symptoms often soon disappear after treatment. However for some patients, they may persist for years and this can have a significant effect on their quality of life. The reasons for these symptoms are not well understood.

This study proposes to examine the effects of chemotherapy on the brain and how the changes in the brain affect one's ability to move one's arms and fingers. By better understanding the negative consequences of chemotherapy on the brain and nervous system, the hope is to help pharmaceutical companies develop safer cancer treatment drugs.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Exposure: Adjuvant chemotherapy treatment; Drug: Exposure: Adjuvant hormonal therapy treatment

Detailed Description

Adjuvant chemotherapy (CTh) is an established postoperative treatment often prescribed to cancer patients to reduce risk of relapse. However, a great proportion of patients report experiencing cognitive, psychomotor, and other functional impairments associated with CTh. Some symptoms may persist for years after treatment and can have dramatic consequences on cancer survivors' quality of life. Despite numerous studies reporting various symptoms during/after CTh treatment, mechanisms underlying these symptoms are not well understood. Recent animal and human brain imaging studies suggest that CTh may have direct neurotoxic effects on the brain, in particular on brain white matter (WM). However, to date, no longitudinal studies have been done to examine the effects of CTh on cortical/subcortical WM integrity in human patients. Furthermore, no effort has yet been made to correlate a given WM structure with its corresponding neurophysiological function (NPF) and behavior. This study proposes longitudinal experiments in women diagnosed with breast cancer to examine the effects of CTh on the corpus callosum (CC) and corticospinal tract (CST) (Aim 1), on NPF that directly depends on the quality of CC/CST structure, and on psychomotor behavior critically relying on CC/CST function (conductivity) (Aim 2). The relationship between CC/CST structural integrity and their corresponding NPF and psychomotor behavior will also be examined (Aim 3). The general underlying hypotheses of the study are that (1) CTh has a direct neurotoxic effect on the CC and CST, resulting in microstructural degeneration and (2) structural damage to the CC and CST impairs relevant neurophysiological function and behavior. This research is expected to yield significant information regarding neural structural and physiological causes of CTh-related side effects; known this information would help more effectively manage the symptoms. By demonstrating direct evidence of detrimental consequences of CTh on the central nervous system, it is hoped that the evidence would encourage pharmaceutical companies to develop safer cancer treatment drugs.

• Study Type: Observational
• Enrollment (Anticipated): 60

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • West Orange, New Jersey, United States, 07052
      • Recruiting
      • Kessler Foundation
      • Contact: Didier Allexandre, PhD; Phone Number: 973-324-3525; Email: dallexandre@kesslerfoundation.org
      • Principal Investigator: Guang Yue, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Newly diagnosed breast cancer patients

Description

Inclusion Criteria:

• For all participants

  1. Female aged 20-70
  2. Right handed as determined by the Edinburgh Inventory [40]
  3. Proficient in English

• For Cancer patients

  1. Had breast cancer surgery
  2. Stage I, II, IIIa
  3. Non metastatic cancer
  4. Chemotherapy Patients: Scheduled to receive or receiving breast cancer chemotherapy with Anthracycline and/or Taxane
  5. Hormonal Therapy Patients: Scheduled to receive or receiving hormonal therapy with Aromatase inhibitor
  6. For patients recruited before adjuvant therapy: Adjuvant therapy starts at least 2 weeks after surgery
  7. For patients recruited after adjuvant therapy started: Before completing/within 1 month post chemotherapy Within 4 months after starting hormonal therapy

Exclusion Criteria:

1. Symptoms for mild or severe depression as determined by a Patient Health Questionnaire (PHQ-8) score >14
2. Significant impairment in ability to understand and analyze information as determined by a Folstein Mini-Mental State Exam score <21.
3. Prior history of cancer (except breast cancer for breast cancer patients), trauma, neurological, psychiatric, physical or psychological diseases or other conditions that may influence nervous system structure and function
4. Current medication believed to affect cognitive/psychomotor function (i.e., opioid analgesics, anxiolytics or antidepressants)
5. History of alcohol, smoking and drug abuse
6. Transcranial Magnetic Stimulation or MRI contraindication

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Chemotherapy; Breast Cancer patients undergoing conventional postsurgical adjuvant chemotherapy treatment	Drug: Exposure: Adjuvant chemotherapy treatment
Hormonal Therapy; Breast Cancer patients undergoing conventional postsurgical adjuvant hormonal therapy treatment (with no Chemotherapy)	Drug: Exposure: Adjuvant hormonal therapy treatment
Healthy Control; Healthy age, height and body-mass matched healthy controls

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Structural Integrity of the Corpus Collusum as measure by MRI-DTI	Pre to Post chemotherapy change (or at 6 months for hormonal therapy/control)
Change in Structural Integrity of the cortico-spinal tract as measure by MRI-DTI	Pre to Post chemotherapy change (or at 6 months for hormonal therapy/control)
Change in out-of-phase bimanual finger tapping task performance	Pre to Post chemotherapy change (or at 6 months for hormonal therapy/control)
Change in interhemispheric EEG coherence between the left and right motor brain areas	Pre to Post chemotherapy change (or at 6 months for hormonal therapy/control)
Change in corticomuscular conduction time using Transcranial Magnetic Stimulation	Pre to Post chemotherapy change (or at 6 months for hormonal therapy/control)
Change in response time to a simple reaction time	Pre to Post chemotherapy change (or at 6 months for hormonal therapy/control)

Collaborators and Investigators

• Sponsor: Kessler Foundation
• Investigators: Principal Investigator: Guang Yue, PhD, Kessler Foundation

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Anticipated): September 1, 2018
• Study Completion (Anticipated): September 1, 2018

Study Registration Dates

• First Submitted: September 6, 2016
• First Submitted That Met QC Criteria: September 6, 2016
• First Posted (Estimate): September 12, 2016

Study Record Updates

• Last Update Posted (Actual): January 23, 2018
• Last Update Submitted That Met QC Criteria: January 18, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Chemotherapy; Neuroimaging; Hormonal Therapy; Chemobrain
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: R-739-12

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided