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

Sponsor

University of California, San Francisco (Other)

Overall Status

Completed

CT.gov ID

NCT00755313

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

85.2

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
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	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

Detailed Description

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.

Study Design

Study Type:

Observational

Actual Enrollment :

81 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Effects of Chemotherapy on Brain Structure and Function

Study Start Date :

May 1, 2007

Actual Primary Completion Date :

Sep 1, 2012

Actual Study Completion Date :

Jun 6, 2014

Outcome Measures

Primary Outcome Measures

Change in glucose metabolism [Up to 18 months after treatment]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

35 Years to 80 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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