Chemotherapy's Long-Term Effects on the Brain

A UCLA study has shown that chemotherapy can change the blood flow and metabolism of the brain in ways that can linger for 10 years or more after treatment. This could help explain the confusion, sometimes called "chemo brain," reported by many chemotherapy patients.

Positron emission tomography (PET) was used to scan the brains of 21 women who had undergone breast cancer surgery five to 10 years earlier. Sixteen had been treated with chemotherapy regimens. Thirteen control subjects, who never had breast cancer or chemotherapy, were also scanned.

The scans took place as the women performed short-term memory exercises, and while they were resting. The scans showed that there was a rapid jump in activity in the frontal cortexes and cerebellums of the chemotherapy patients as they performed the memory tests, indicating that they were working harder than the control patients to recall the same information.

The study also revealed that women who underwent hormonal therapy in addition to chemotherapy showed changes to their basal ganglia, a part of the brain that bridges thought and action.

Breast Cancer Research and Treatment September 29, 2006Daniel H. S. Silverman1, 6 Contact Information, Christine J. Dy1, Steven A. Castellon2, 5, Jasmine Lai1, Betty S. Pio1, Laura Abraham3, Kari Waddell3, Laura Petersen3, Michael E. Phelps1 and Patricia A. Ganz3(1) Department of Molecular and Medical Pharmacology, University of California, David Geffen School of Medicine, Los Angeles, CA, USA(2) Department of Psychiatry and Biobehavioral Science, University of California, David Geffen School of Medicine, Los Angeles, CA, USA(3) Division of Cancer Prevention & Control Research, Jonsson Comprehensive Cancer Center, University of California, David Geffen School of Medicine, Los Angeles, CA, USA(4) UCLA Schools of Medicine & Public Health, University of California, David Geffen School of Medicine, Los Angeles, USA(5) Greater Los Angeles VA Healthcare System, Los Angeles, CA, USA(6) Ahmanson Biological Imaging Division, CHS AR-144 UCLA Medical Center, MC694215, Los Angeles, CA 90095-6942, USA

Received: 10 August 2006 Accepted: 11 August 2006 Published online: 29 September 2006Abstract Purpose To explore the relationship of regional cerebral blood flow and metabolism with cognitive function and past exposure to chemotherapy for breast cancer.

Patients and methods Subjects treated for breast cancer with adjuvant chemotherapy remotely (5-10 years previously) were studied with neuropsychologic testing and positron emission tomography (PET), and were compared with control subjects who had never received chemotherapy. [O-15] water PET scans was acquired during performance of control and memory-related tasks to evaluate cognition-related cerebral blood flow, and [F-18] fluorodeoxyglucose (FDG) PET scans were acquired to evaluate resting cerebral metabolism.

PET scans were analyzed by statistical parametric mapping and region of interest methods of analysis.Results During performance of a short-term recall task, modulation of cerebral blood flow in specific regions of frontal cortex and cerebellum was significantly altered in chemotherapy-treated subjects. Cerebral activation in chemotherapy-treated subjects differed most significantly from untreated subjects in inferior frontal gyrus, and resting metabolism in this area correlated with performance on a short-term memory task previously found to be particularly impaired in chemotherapy-treated subjects. In examining drug-class specific effects, metabolism of the basal ganglia was significantly decreased in tamoxifen + chemotherapy-treated patients compared with chemotherapy-only breast cancer subjects or with subjects who had not received chemotherapy, while chemotherapy alone was not associated with decreased basal ganglia activity relative to untreated subjects.

Conclusion Specific alterations in activity of frontal cortex, cerebellum, and basal ganglia in breast cancer survivors were documented by functional neuroimaging 5-10 years after completion of chemotherapy.Science Blog October 5, 2006USA Today October 5, 2006

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