Effects of Chemotherapy on the Brain in Women With Newly Diagnosed Early-Stage Breast Cancer

OBJECTIVES:

Primary

- To prospectively evaluate the acute (1 month after chemotherapy) and relatively
long-term (18 months after chemotherapy) effects of standard-dose chemotherapy and/or
hormonal therapy with aromatase inhibition on brain function using positron emission
tomography (PET) and the glucose metabolism tracer fludeoxyglucose F 18 in women with
newly diagnosed, early stage breast cancer.

Secondary

- To evaluate the acute and relatively long-term effects of chemotherapy and/or hormonal
therapy on MRI measurements of hippocampal volume, cortical grey matter volume, white
matter signal hyperintensities, ventricular volume, and whole brain volume in these
patients.

- To evaluate the acute and relatively long-term effects of chemotherapy and/or hormonal
therapy with aromatase inhibition on cognitive function in these patients.

- To explore the characteristics of these patients that renders them more vulnerable to
chemotherapy and/or estrogen suppression-induced cognitive decline.

OUTLINE: Patients are stratified according to planned adjuvant chemotherapy (chemotherapy and
hormonal therapy vs hormonal therapy vs chemotherapy vs no therapy) and the hormone receptor
status (positive vs negative).

Patients (groups A-C) undergo bioavailable estradiol measurements, PET scans, and MRI scans
at baseline and 1 and 18 months after treatment. Patients also undergo cognitive,
neuropsychological, sociodemographic, and quality of life assessments using a battery of
study tests and questionnaires at baseline and at 1, 9, and 18 months after treatment. Group
D participants (controls) undergo the same testing at equivalent intervals.

DISEASE CHARACTERISTICS:

- Diagnosis of breast cancer, meeting 1 of the following criteria:

- Group A

- Stage I, II, or III invasive disease

- Hormone receptor-positive disease

- Planned adjuvant chemotherapy including an anthracycline and taxane using
either dose-dense or docetaxel, doxorubicin hydrochloride, and
cyclophosphamide (TAC) regimens with or without trastuzumab (Herceptin®) for
4 months; docetaxel and cyclophosphamide (TC) with or without trastuzumab
for 3 months; doxorubicin hydrochloride and cyclophosphamide (AC) for 3
months; or doxorubicin hydrochloride, carboplatin, and trastuzumab (TCH) for
4 months (trastuzumab may be given for 1 year and is not considered
chemotherapy for the purpose of this study)

- Planned treatment with adjuvant aromatase inhibitors (AI) for 5 years

- Group B

- Stage I or II invasive disease

- Planned treatment with adjuvant AI with or without radiotherapy

- Group C

- Stage I, II, or III disease

- Hormone-receptor negative

- Planned adjuvant chemotherapy as in group A

- No treatment with AI planned

- Group D

- Healthy controls free of any major medical or psychiatric disorders

- Not taking prescription medications, including hormone-replacement therapy,
or other substances that might influence performance on neuropsychological
tests

- Balanced with the patient groups on age, education, ethnicity, and
sociodemographic background

PATIENT CHARACTERISTICS:

- No history of psychiatric illness other than minor depression

- No history of psychiatric illness other than minor depression in immediate family
members

- No history of neurologic disease

- No history of drug or alcohol abuse

- No significant medical illness other than breast cancer

- No heart pacemaker or metallic implants or particles in the body

- No heart rhythm disturbance

- No claustrophobia

- No prior serious head injury

- No tattoos or permanent cosmetics

- No unremovable body jewelry

- No cognitive impairment

- Able to read and speak English

- No condition that compromises compliance with the objectives and procedures of this
study, as judged by the principal investigator

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior chemotherapy, CNS radiotherapy, or intrathecal therapy

- Premenopausal women receiving aromatase inhibitors must also be receiving ovarian
suppression

- No concurrent narcotics or major antipsychotic medications that may impair cognition