Breast Cancer, Cognitive Symptom
Conditions
Brief summary
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.
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.
Interventions
BEHAVIORALHealth 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.
BEHAVIORALMindfulness-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.
Sponsors
National Institute of Nursing Research (NINR)
New York University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Investigator, Outcomes Assessor)
Masking description
Participants will complete the baseline assessment and be randomly assigned to study group in a permuted block design stratified by receipt of chemotherapy (i.e., two strata). It will not be possible to blind study participants or interventionists to group assignment. To reduce bias, research staff who conduct assessments, including the PI, will be blinded to group assignment (i.e., single blind). Participants will be reminded not to reveal their group assignment to study staff conducting assessments. The study biostatistician will have no direct contact with study participants and will not be blinded to group assignment. The biostatistician will produce and maintain the randomization codes for the permuted blocks. Randomization may only be unmasked by the biostatistician at the completion of data collection, or for reporting of serious adverse events or unanticipated problems for which it will be essential to provide information to the PI on group assignment.
Intervention model description
A pilot, single-center randomized controlled trial of the preliminary efficacy of an eight-week, group-based Mindfulness-Based Stress Reduction intervention versus Health Enhancement Program active control (i.e., two groups, parallel design) to improve neural markers of changes in cognitive function in postmenopausal women receiving aromatase inhibitor therapy for breast cancer. Participants will be stratified in a permuted block design by receipt of chemotherapy (i.e., two strata). Data will be collected at up to three time points using a repeated measures design (i.e., pre-intervention, post-intervention, approximately three months after the intervention). The study groups will meet at NYU for MBSR or HEP. Neuropsychological, self-report, and biospecimen data collection will be conducted at the Bluestone Center. Neuroimaging data will be collected at the NYU Center for Brain Imaging.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 79 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Functional Neural Activation Parameter Estimate | baseline, 3 months | 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Flanker Inhibitory Control and Attention Test | baseline, 6 months | 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 |
| Cognitive Function | baseline, 3 months, 6 months | 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 |
| List Sorting Working Memory Test | baseline, 6 months | 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 |
| Depression | baseline, 3 months, 6 months | 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 |
| Gene Expression | baseline, 3 months, 6 months | 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 |
| Anxiety | baseline, 3 months, 6 months | 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 |
Countries
United States
Participant flow
Recruitment details
NYU was activated as a site in September 2017. Recruitment and screening began in January 2018. Enrollment started in April 2018 and ended in October 2019. Bellevue Hospital site approval was received in July 2019. Enrollment began then in its affiliated clinics and ended in October 2019.
Participants by arm
| Arm | Count |
|---|---|
| MBSR Mindfulness-Based Stress Reduction
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. | 12 |
| Health Enhancement Program Health Enhancement Program
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. | 11 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Inability to complete MRI | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | MBSR | Total | Health Enhancement Program |
|---|---|---|---|
| Age, Continuous | 65.9 years STANDARD_DEVIATION 4.85 | 61 years STANDARD_DEVIATION 9.46 | 55.6 years STANDARD_DEVIATION 10.51 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 22 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 20 Participants | 10 Participants |
| Region of Enrollment United States | 12 participants | 23 participants | 11 participants |
| Sex: Female, Male Female | 12 Participants | 23 Participants | 11 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 11 |
| other Total, other adverse events | 0 / 12 | 0 / 11 |
| serious Total, serious adverse events | 0 / 12 | 0 / 11 |
Outcome results
Primary
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
Time frame: baseline, 3 months
Population: participants with usable neuroimaging data after quality control
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MBSR | Functional Neural Activation Parameter Estimate | baseline | -1.2 beta weights | Standard Deviation 2.27 |
| MBSR | Functional Neural Activation Parameter Estimate | 3 months | -0.8 beta weights | Standard Deviation 1.95 |
| Health Enhancement Program | Functional Neural Activation Parameter Estimate | baseline | -1.8 beta weights | Standard Deviation 2.28 |
| Health Enhancement Program | Functional Neural Activation Parameter Estimate | 3 months | -0.7 beta weights | Standard Deviation 2.27 |
Comparison: baselinep-value: 0.46t-test, 2 sided
Comparison: 3 monthsp-value: 0.896t-test, 2 sided
Other Pre-specified
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
Time frame: baseline, 3 months, 6 months
Population: Differences in sample size due to attrition
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MBSR | Anxiety | baseline | 51.3 T-score | Standard Deviation 5.4 |
| MBSR | Anxiety | 3 months | 48.8 T-score | Standard Deviation 6.91 |
| MBSR | Anxiety | 6 months | 46.7 T-score | Standard Deviation 7.56 |
| Health Enhancement Program | Anxiety | baseline | 53.1 T-score | Standard Deviation 5.96 |
| Health Enhancement Program | Anxiety | 3 months | 53.9 T-score | Standard Deviation 12.28 |
| Health Enhancement Program | Anxiety | 6 months | 50.3 T-score | Standard Deviation 12.66 |
Comparison: baselinep-value: 0.452t-test, 2 sided
Comparison: 3 monthsp-value: 0.253t-test, 2 sided
Comparison: 6 monthsp-value: 0.469t-test, 2 sided
Other Pre-specified
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
Time frame: baseline, 3 months, 6 months
Population: Differences in sample size due to attrition
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MBSR | Cognitive Function | baseline | 47.0 T-score | Standard Deviation 6.49 |
| MBSR | Cognitive Function | 3 months | 45.4 T-score | Standard Deviation 5.12 |
| MBSR | Cognitive Function | 6 months | 47.4 T-score | Standard Deviation 6.37 |
| Health Enhancement Program | Cognitive Function | baseline | 45.9 T-score | Standard Deviation 8.2 |
| Health Enhancement Program | Cognitive Function | 3 months | 46.0 T-score | Standard Deviation 8.93 |
| Health Enhancement Program | Cognitive Function | 6 months | 46.4 T-score | Standard Deviation 7.57 |
Comparison: baselinep-value: 0.715t-test, 2 sided
Comparison: 3 monthsp-value: 0.861t-test, 2 sided
Comparison: 6 monthsp-value: 0.79t-test, 2 sided
Other Pre-specified
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
Time frame: baseline, 3 months, 6 months
Population: Differences in sample size due to attrition
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MBSR | Depression | baseline | 46.3 T-score | Standard Deviation 6.31 |
| MBSR | Depression | 3 months | 46.0 T-score | Standard Deviation 6.78 |
| MBSR | Depression | 6 months | 44.9 T-score | Standard Deviation 7.24 |
| Health Enhancement Program | Depression | baseline | 45.3 T-score | Standard Deviation 3.24 |
| Health Enhancement Program | Depression | 3 months | 49.7 T-score | Standard Deviation 10.41 |
| Health Enhancement Program | Depression | 6 months | 48.4 T-score | Standard Deviation 8.91 |
Comparison: baselinep-value: 0.628t-test, 2 sided
Comparison: 3 monthsp-value: 0.345t-test, 2 sided
Comparison: 6 monthsp-value: 0.384t-test, 2 sided
Other Pre-specified
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
Time frame: baseline, 6 months
Population: Differences in sample size due to attrition
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MBSR | Flanker Inhibitory Control and Attention Test | baseline | 46.5 T-score | Standard Deviation 8.17 |
| MBSR | Flanker Inhibitory Control and Attention Test | 6 months | 43.3 T-score | Standard Deviation 3.83 |
| Health Enhancement Program | Flanker Inhibitory Control and Attention Test | baseline | 41.9 T-score | Standard Deviation 7.64 |
| Health Enhancement Program | Flanker Inhibitory Control and Attention Test | 6 months | 42.4 T-score | Standard Deviation 11.27 |
Comparison: baselinep-value: 0.18t-test, 2 sided
Comparison: 6 monthsp-value: 0.822t-test, 2 sided
Other Pre-specified
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
Time frame: baseline, 3 months, 6 months
Population: participants with usable gene expression data after quality control
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MBSR | Gene Expression | baseline | 106.1 raw gene counts | Standard Deviation 74.98 |
| MBSR | Gene Expression | 3 months | 196.0 raw gene counts | Standard Deviation 210.74 |
| MBSR | Gene Expression | 6 months | 114.4 raw gene counts | Standard Deviation 81.11 |
| Health Enhancement Program | Gene Expression | baseline | 137.3 raw gene counts | Standard Deviation 77.4 |
| Health Enhancement Program | Gene Expression | 3 months | 176.3 raw gene counts | Standard Deviation 114.57 |
| Health Enhancement Program | Gene Expression | 6 months | 218.3 raw gene counts | Standard Deviation 86.28 |
Comparison: baselinep-value: 0.398t-test, 2 sided
Comparison: 3 monthsp-value: 0.811t-test, 2 sided
Comparison: 6 monthsp-value: 0.027t-test, 2 sided
Other Pre-specified
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
Time frame: baseline, 6 months
Population: differences in sample size due to attrition
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MBSR | List Sorting Working Memory Test | baseline | 48.7 T-score | Standard Deviation 6.05 |
| MBSR | List Sorting Working Memory Test | 6 months | 50.5 T-score | Standard Deviation 8.57 |
| Health Enhancement Program | List Sorting Working Memory Test | baseline | 51.5 T-score | Standard Deviation 8.57 |
| Health Enhancement Program | List Sorting Working Memory Test | 6 months | 56.3 T-score | Standard Deviation 10.75 |
Comparison: baselinep-value: 0.374t-test, 2 sided
Comparison: 6 monthsp-value: 0.236t-test, 2 sided