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.
