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