Exercise Program in Cancer and Cognition

The specific aims include:

1. Compared to usual care, examine whether the 6-month exercise intervention improves
cognitive function over the first six months of AI therapy in postmenopausal women with
early stage breast cancer.

Hypothesis 1. Exercise will improve cognitive function in women receiving AI therapy in
a domain specific fashion such that attention, executive and memory functions will be
influenced more than other domains.

2. Compared to usual care, examine the direct effects of exercise on neuroimaging metrics
of brain health including regional gray matter volume, white matter architecture and
functional dynamics of the brain and the pro-inflammatory biomarkers (IL-6 and CRP as
primary outcomes; TNF-α as secondary), and explore the direct effects of exercise on
symptoms (fatigue, sleep problems, depression, anxiety).

Hypothesis 2. Exercise will improve neuroimaging metrics of brain health and
pro-inflammatory biomarkers.

3. Compared to usual care, explore whether the effects of exercise on cognitive function
are mediated by a) neuroimaging metrics of cognitive function, b) IL-6, CRP and TNF-α
levels and c) symptoms (fatigue, sleep problems, depression, anxiety), and moderated by
E2 levels over the first six months of AI therapy.

Inclusion Criteria:

1. Postmenopausal female

2. Maximum age 75 years

3. Able to speak and read English

4. Minimum completion of 8 years of education

5. Diagnosed with Stage 0, 1, 2 or 3a Breast Cancer

6. Eligible to receive aromatase inhibitor therapy

7. At least two weeks post-breast conserving surgery or three weeks post-breast
conserving surgery with sentinel lymph node biopsy or four weeks post-mastectomy

8. Medical clearance by their breast cancer surgeon

Exclusion Criteria:

1. Prior diagnoses of cancer (exception with some skin cancers)

2. Clinical evidence of distant metastases

3. Self-report of hospitalization for psychiatric illness within the last two years

4. History of neurologic illness

5. Any breast cancer surgery complications including persistent seroma requiring
aspiration, wound dehiscence, infection, prolonged drain output, lymphedema (confirmed
by participant's surgical oncologist)

6. Reconstructive surgery

7. A medical condition that would preclude them from exercising including a history of
coronary artery or pulmonary disease, congestive heart failure, angina, uncontrolled
arrhythmia, or other symptoms that indicate increased risk for an acute cardiovascular
event

8. Current treatment for Type II Diabetes

9. Eating disorders or a history of substance abuse

10. Any use of an assisted walking device

11. Recent history of falls or balance problems

12. Current beta-blocker use

Additional Exclusion Criteria for Neuroimaging subgroup:

1. Presence of metal implants (i.e., pacemaker, some stents)