MBSR During AI Therapy for Breast Cancer

Mindfulness-Based Stress Reduction To Improve Cognitive Function for Postmenopausal Women With Breast Cancer

This study will use non-invasive neuroimaging (i.e., MRI) to examine whether Mindfulness-Based Stress Reduction (MBSR) improves neural markers of cognitive function for postmenopausal women taking aromatase inhibitor (AI) therapy for breast cancer. The pilot randomized controlled trial will obtain preliminary efficacy of MBSR versus Health Enhancement Program (HEP) active control to improve neural markers of cognitive function. The final sample will include 32 postmenopausal women with breast cancer. MBSR and HEP groups will meet for a matched schedule of 8 weekly 2.5-hour sessions and a one-day weekend retreat. Specimen and data collection will be done at three time points: pre-randomization (i.e., within three weeks before beginning the intervention), within three weeks after completion of the intervention, and approximately three months (+/- three weeks) post intervention. Change scores for neuroimaging parameter estimates will be correlated with change scores for measures of cognitive function and affect. Differential expression of genes will be correlated with neuroimaging parameter estimates.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Cognitive Symptom
• Intervention / Treatment: Behavioral: Mindfulness-Based Stress Reduction; Behavioral: Health Enhancement Program

Detailed Description

Adjuvant aromatase inhibitor (AI) therapy improves disease-free and overall survival for postmenopausal women after surgery for hormone receptor-positive breast cancer. Among symptoms associated with AI therapy are changes in cognitive function. Up to 25% of postmenopausal women with breast cancer report that they experience changes in cognitive function during AI therapy. Studies using neuropsychological tests found subtle deteriorations in verbal and visual learning and memory-as well as concentration, working memory, and executive function-for as many as a third of these patients. Changes in cognitive function may be associated with changes in affect (e.g., worry, depressive symptoms). Neural markers of cognitive changes, including changes in brain function and structure, may underlie changes in cognitive function.

The investigators' recent preliminary neuroimaging work to describe neural markers of cognitive changes suggests that postmenopausal women with breast cancer have inefficient cognitive-emotion processing before AI therapy, as evidenced by greater neural activity in the hippocampus (working memory) and amygdala (emotion processing) during task performance compared to controls. During AI therapy, patients show differential activation compared to controls in the dorsolateral prefrontal cortex (executive function and working memory), medial prefrontal cortices (cortical control of amygdala responses), and hippocampus.

Stress responses could partially explain relationships between AI therapy and neural markers of cognitive changes. The Mindfulness Stress-Buffering Account suggests that interventions such as Mindfulness-Based Stress Reduction (MBSR) may improve stress responses by attenuating negative appraisals of stress and reducing reactivity to stressful situations. For example, mindfulness meditation improved psychological stress responses in women with breast cancer. It improved some measures of cognitive function. Mindfulness practices reduced physiological markers of stress responses, including inflammatory markers in women with breast cancer and in stressed community adults, as well as cortisol reactivity for breast cancer survivors and during chemotherapy for colorectal cancer. Although similar neural deficits as were found in the investigators' preliminary work have been shown to improve in stressed adult populations using MBSR, it is not known whether the intervention improves neural deficits in women taking AI therapy (estrogen, production of which is blocked by AI therapy, is neuroprotective and promotes neural plasticity). Genetic variability was previously found to moderate the effect of MBSR on self-reported cognitive function. Therefore, it is possible that inter-individual variability in the expression of genes involved in stress responses could moderate relationships between AI therapy and neural markers of cognitive changes during MBSR. Taken together, MBSR may improve neural markers of cognitive changes shown in preliminary work to be deficient in postmenopausal women before and during AI therapy for breast cancer by targeting stress responses. Changes in these neural markers may correspond to improved self-report and neuropsychological measures of cognitive function.

Hypothesis: Stress reduction, moderated by gene expression, blunts the impact of AI therapy on neural markers of cognitive function, thereby improving cognitive function and affect in women with breast cancer.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10010
      • New York University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Female
2. <80 years of age by date of baseline assessment visit
3. Able to speak and read English
4. Post-menopausal (defined as [A] amenorrhea persisting for an entire year, [B] oophorectomy or ovarian suppression/ablation, or [C] hysterectomy and age >51 years)
5. Diagnosed with DCIS (stage 0) or stage I, II, or III breast cancer
6. Post lumpectomy or mastectomy and any re-excisions
7. Post neoadjuvant or adjuvant chemotherapy, if prescribed
8. Taking aromatase inhibitor (AI) therapy OR AI therapy scheduled to begin before planned post-intervention assessment visit

Exclusion Criteria:

1. Stage IV (metastatic) breast cancer
2. Diagnosis of a major psychiatric disorder (e.g., bipolar I disorder, schizophrenia, schizoaffective disorder)
3. Suicide attempt within the last 10 years
4. Hospitalization or residential treatment for psychiatric illness, eating disorder, or substance abuse within the last 2 years
5. History of neurological disease (e.g., Parkinson's disease, dementia)
6. History of head trauma
7. Claustrophobia
8. Unable to lie on the back
9. Ever been told not to get an MRI

10. MRI-incompatible metal implant*

    • If a potential participant reports implanted metal objects, which might be affected by MRI magnets, the study personnel and MRI technologist will screen over the phone or in person to determine whether the potential participant would be safe during the MRI scan. A current list of implants compatible with MRI will be consulted (http://www.mrisafety.com/TMDL_list.php).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MBSR; Mindfulness-Based Stress Reduction	Behavioral: Mindfulness-Based Stress Reduction; The MBSR group will receive training from a certified instructor during a group-based, 2.5-hour manualized educational activity weekly for eight weeks. Activities include body scans, gentle stretching, yoga, and mindful awareness. Participants will be asked to complete daily 45-minute, audio-guided mindfulness activities and a one-day weekend retreat to reinforce learning.; Other Names: MBSR
Active Comparator: Health Enhancement Program	Behavioral: Health Enhancement Program; The HEP control, which was developed to serve as an active control to MBSR, will receive manualized health education from experts in physical activity, functional movement, music therapy, and nutrition-without mindfulness instruction-using similar modalities to MBSR training for a matched schedule.; Other Names: HEP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional Neural Activation Parameter Estimate	global maximum cluster-level neural activation during task-based functional magnetic resonance imaging for MBSR group compared to Health Enhancement Program group in a whole-brain analysis; paradigm: Emotional Faces N-Back; conditions: happy face distractors minus no face distractors; value has no minimum or maximum; value has no reference ranges; higher values indicate more neural activation	baseline, 3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
List Sorting Working Memory Test	from National Institutes of Health (NIH) Toolbox; Age 7+ v2.1; measures working memory; T-score range 23-77; 50 indicates the population mean with a standard deviation of 10; higher scores indicate better working memory performance; scores below 40 suggest cognitive impairment	baseline, 6 months
Flanker Inhibitory Control and Attention Test	from National Institutes of Health (NIH) Toolbox; Age 12+ v2.1; measures attention; T-score range 23-77; 50 indicates the population mean with a standard deviation of 10; higher scores indicate better attention performance; scores below 40 suggest cognitive impairment	baseline, 6 months
Cognitive Function	From the Quality of Life in Neurological Disorders (Neuro-QoL) Bank; v2.0; patient-reported outcome; measures executive function and general cognitive concerns; T-score range 17.3-64.2; 50 indicates the population mean with a standard deviation of 10; higher scores indicate better self-reported cognitive function; scores 41-45 suggest mild cognitive impairment, 31-40 suggest moderate cognitive impairment, and 30 or below suggest severe cognitive impairment	baseline, 3 months, 6 months
Anxiety	From the Quality of Life in Neurological Disorders (Neuro-QoL) Bank; v1.0; patient reported outcome; T-score range 36.4-76.8; 50 indicates the population mean with a standard deviation of 10; higher scores indicate worse self-reported anxiety; scores 55-59 suggest mild anxiety, 60-69 suggest moderate anxiety, and 70 or above suggest severe anxiety	baseline, 3 months, 6 months
Depression	From the Quality of Life in Neurological Disorders (Neuro-QoL) Bank; v1.0; patient-reported outcome; measures depressive symptoms; T-score range 36.9-75.0; 50 indicates the population mean with a standard deviation of 10; higher scores indicate worse depressive symptoms; scores 55-59 suggest mild depressive symptoms, 60-69 suggest moderate depressive symptoms, and 70 or above suggest severe depressive symptoms	baseline, 3 months, 6 months
Gene Expression	AMIGO1 gene expression in raw gene counts for MBSR group compared to Health Enhancement Program group in a whole transcriptome analysis using ribonucleic acid sequencing (RNA-Seq); minimum 0, no maximum; value has no reference ranges; higher values indicate more gene expression	baseline, 3 months, 6 months

Collaborators and Investigators

• Sponsor: New York University
• Collaborators: National Institute of Nursing Research (NINR)
• Investigators: Principal Investigator: John D Merriman, PhD, RN, New York University Meyers College of Nursing

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2018
• Primary Completion (Actual): December 10, 2019
• Study Completion (Actual): September 8, 2020

Study Registration Dates

• First Submitted: August 8, 2017
• First Submitted That Met QC Criteria: August 15, 2017
• First Posted (Actual): August 18, 2017

Study Record Updates

• Last Update Posted (Actual): November 2, 2022
• Last Update Submitted That Met QC Criteria: October 31, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Neurologic Manifestations; Breast Diseases; Breast Neoplasms; Neurobehavioral Manifestations
• Other Study ID Numbers: s17-00995; 4R00NR015473-03 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Even though the R00 study is not anticipated to reach the threshold for required genomic data sharing, the study will have in place plans for sharing de-identified data for secondary analyses with qualified investigators. The consent language for the R00 study will be worded for possible broad data sharing.
• IPD Sharing Time Frame: The timeline for submission to an NIH-designated data repository will allow first for publication of findings related to the aims of the R00 study, as well as submission of findings as preliminary data for anticipated grant application(s).
• IPD Sharing Access Criteria: The investigators plan to submit genomic data and relevant phenotypic data (e.g., clinical characteristics of the sample) generated in the R00 study to an NIH-designated data repository in a timely manner. The submission process will likely include registration in the database of Genotypes and Phenotypes (dbGaP) and submission to Gene Expression Omnibus (GEO) for controlled access to the data.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No