This study will use advanced MRI techniques to characterize the changes that occur to the structure and functionality of the brain in older breast cancer patients receiving adjuvant chemotherapy, and determine the relationship between the brain changes and severity of chemotherapy toxicity. Our results will be an early step towards identifying neuroimaging markers of aging, breast cancer and chemotherapy treatment, and will contribute to our understanding of the underlying pathophysiology of cognitive changes and chemotherapy toxicity in vulnerable, older adults with cancer. Furthermore, the work will lay the foundation for future, larger scale clinical studies of cognitive changes and chemotherapy toxicity in the aging cancer population.

Breast cancer is the leading cancer diagnosed among woman in the US and is the second leading cause of cancer deaths. Adjuvant chemotherapy has been proven to decrease the risks of relapse and mortality from breast cancer. However, older adults are at increased risk for chemotherapy toxicity, including an increased risk of treatment-related mortality. At present, there is only preliminary evidence regarding which brain structures and functions are affected by chemotherapy and toxicity in breast cancer patients. However, this prior research did not specifically study older women. Thus, there is a need to establish a more sensitive test that has reproducible biomarkers, to identify the older breast cancer patients who are at higher risk for chemotherapy toxicity Our long term goal is to identify highly sensitive and reproducible brain MRI biomarkers that are associated with chemotherapy toxicity in aging cancer patients. Toward that goal, the objective of this study is to define the changes that occur on brain MRI and to determine the relationship between brain MRI changes and chemotherapy toxicity in older adults with breast cancer. We aim to 1) define structural and functional changes that occur on brain MRI of older women with breast cancer receiving adjuvant chemotherapy and; 2) determine the relationship between the severity of structural and functional changes on brain MRI and chemotherapy toxicity. We expect that the severity of structural and functional changes to the brain MRI in our patients will correlate with the severity of chemotherapy toxicity. The proposed study is significant because it focuses on the unknown relationship between brain MRI changes and chemotherapy toxicity in older women with breast cancer. It is innovative because it proposes advanced MRI techniques to study and identify the novel potential biomarkers for chemotherapy toxicity in older adults with breast cancer. It will have a positive impact by helping to clarify the underlying pathophysiology of cognitive decline caused by chemotherapy toxicity. The data generated from this pilot study will also help to serve as a foundation for future large scale studies of cognition and chemotherapy in older adults.

Inclusion Criteria:

• 1) Patients with stage I-III breast cancers who are to receive adjuvant chemotherapy;
• 2) Able to understand English (the functional MRI task paradigms and neurocognitive testing are not validated in languages other than English);
• 3) Able to provide informed consent;
• 4) Patients age ≥ 65 and of any performance status.

Exclusion Criteria:

• 1) Patients with metastatic disease;
• 2) Patients with MRI exclusion criteria such as claustrophobia, cardiac pacemaker, and orbital metal implants.

Using a prospective longitudinal study design, 25 patients will be recruited for this study from the outpatient medical oncology practice at City of Hope Medical Center.