MBSR During AI Therapy for Breast Cancer
Condition: Breast Cancer; Cognitive Symptom
MeSH terms: Breast Neoplasms; Neurobehavioral Manifestations
Study type: Interventional

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.
    

Intervention name(s): Health Enhancement Program; Mindfulness-Based Stress Reduction
Intervention type(s): Behavioral; Behavioral
Intervention description(s): 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.; 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 intervention name(s): HEP; MBSR
Allocation: Randomized
Intervention model: Parallel 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.
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Supportive Care