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

Study Overview
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Brief Summary
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RATIONALE: Gathering information over time from laboratory tests, imaging scans, and assessment tests may help doctors learn more about the side effects of chemotherapy and plan the best treatment. PURPOSE: This clinical trial is studying the effects of chemotherapy on the brain in women with newly diagnosed early-stage breast cancer.

Detailed Description
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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.

Official Title
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Effects of Chemotherapy on Brain Structure and Function

Conditions
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Breast Cancer, Chemotherapeutic Agent Toxicity, Cognitive/Functional Effects, Fatigue, Long-term Effects Secondary to Cancer Therapy in Adults, Neurotoxicity, Psychosocial Effects of Cancer and Its Treatment

Intervention / Treatment
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* Biological: trastuzumab
* Drug: aromatase inhibition therapy
* Drug: carboplatin
* Drug: cyclophosphamide
* Drug: docetaxel
* Drug: doxorubicin hydrochloride
* Other: metabolic assessment
* Other: questionnaire administration
* Other: study of socioeconomic and demographic variables
* Procedure: cognitive assessment
* Procedure: positron emission tomography
* Radiation: fludeoxyglucose F 18


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: trastuzumab|nan|
|Drug: aromatase inhibition therapy|nan|
|Drug: carboplatin|nan|
|Drug: cyclophosphamide|nan|
|Drug: docetaxel|nan|
|Drug: doxorubicin hydrochloride|nan|
|Other: metabolic assessment|nan|
|Other: questionnaire administration|nan|
|Other: study of socioeconomic and demographic variables|nan|
|Procedure: cognitive assessment|nan|
|Procedure: positron emission tomography|nan|
|Radiation: fludeoxyglucose F 18|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in glucose metabolism |  | Up to 18 months after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MRI measures of the brain (hippocampal volume, cortical gray matter volume, white matter signal hyperintensities, ventricular volume, whole brain volume) |  | Up to 18 months after treatment | 
| Measures of cognitive function over time by Wechsler memory scale, word list memory, Stroop Color Word Test, Boston Naming Test, verbal fluency, FACIT-B functional assessment, Mini Mental State Exam, Hamilton Depression Rating Scale (Ham-D), Beck De ... |  | Up to 18 months after treatment | 
| Cognitive assessments over time by FACIT-B, Ham-D, BDI-II, STAI, FSI, and MASQ, demographic and medical data |  | Up to 18 months after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cognitive/functional effects, fatigue, long-term effects secondary to cancer therapy in adults, psychosocial effects of cancer and its treatment, chemotherapeutic agent toxicity, neurotoxicity, stage IA breast cancer, stage IB breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, estrogen receptor-negative breast cancer, estrogen receptor-positive breast cancer, progesterone receptor-negative breast cancer, progesterone receptor-positive breast cancer