MBSR During AI Therapy for Breast Cancer

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.

Inclusion Criteria:

1. Willingness and ability to participate in study assessments and the eight-week
intervention

2. Female

3. Age 18-79

4. Able to speak and read English

5. Completed at least an eighth-grade education

6. Post-menopausal

7. Diagnosed with DCIS (stage 0) or stage I, II, or III breast cancer

8. Post lumpectomy or mastectomy

9. Post neoadjuvant or adjuvant chemotherapy, if prescribed

10. Scheduled to begin, or within 18 months of beginning, treatment with an aromatase
inhibitor (AI)

11. Written, informed consent

Exclusion Criteria:

1. Stage IV (metastatic) breast cancer

2. Diagnosis of a major psychiatric disorder (e.g., schizophrenia, bipolar I disorder)

3. Hospitalization or residential treatment for psychiatric illness, eating disorder, or
substance abuse in the last two years

4. History of neurological disease (e.g., Parkinson's disease, dementia)

5. History of head trauma

6. Claustrophobia

7. Unable to lie on the back

8. Ever been told not to get an MRI

9. 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/TheList_search.asp).