Chemobrain: Changes in Cerebral White Matter

Fran Lowry

December 22, 2011

December 22, 2011 — Cerebral white matter is altered and cognitive function declines after chemotherapy, according to a new, longitudinal study published online December 19 in the Journal of Clinical Oncology.

The study, which used an advanced imaging technique to document actual physical changes in the brain, along with a detailed cognitive assessment before and after a course of chemotherapy for breast cancer, adds to the emerging body of literature attesting to the effects of chemotherapy on brain structure and function, comments the author of an accompanying editorial.

"We can no longer deny the existence of this long-term effect of cancer treatment; we must work to tailor future treatments to minimize this adverse outcome," Patricia A. Ganz, MD, from the Jonsson Comprehensive Cancer Center at the University of California Los Angeles, notes in her editorial.

Physical Changes in the Brain

Led by Sabine Deprez, MD, from University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Belgium, the new study examined pre- and postchemotherapy self-reported cognitive complaints, neuropsychological test performance, and brain function, as assessed with magnetic resonance diffusion tensor imaging, in 34 young premenopausal women (age, 42.9 ± 4 years) with early-stage breast cancer.

These patients were compared with 16 patients with breast cancer who did not have chemotherapy (age, 42.9 ± 4 years), as well as with 19 age-matched healthy control patients.

Eighteen patients who received chemotherapy and 14 patients who did not receive chemotherapy had started hormonal treatment with tamoxifen after entering the study.

Magnetic resonance diffusion tensor imaging is a technique that allows the visualization and characterization of white matter architecture. It measures fractional anisotropy, which is an indication of derangement of brain structure at a microscopic level, Dr. Deprez and colleagues explain.

All patients had similar cognitive functioning at study entry. However, when tested 4 months later, patients who had received chemotherapy performed significantly worse on attention and concentration tests, psychomotor speed, and memory compared with baseline (P < .05).

There were also significant decreases in fractional anisotropy in the frontal, parietal, and occipital white matter tracts after chemotherapy, but no such changes were noted either in the patients who did not receive chemotherapy or in the control patients.

The study also found that changes in attention and verbal memory correlated with the brain imaging changes that occurred after chemotherapy.

In her editorial, Dr. Ganz points out that the study was "quite small" and was possibly confounded by the fact that half of the patients were receiving tamoxifen at the time of their postchemotherapy assessments. She also notes that the follow-up time was relatively short, and that it is possible that the self-reported cognitive complaints and brain imaging changes could resolve over time, "as has been reported by others."

Are These Changes Caused by a Specific Agent?

The editorialist also writes that at this time, it is uncertain whether the cognitive changes seen after chemotherapy are the result of a specific chemotherapeutic agent or of an overall systemic effect of chemotherapy, and suggests that this aspect needs additional study.

If the brain changes and cognitive decline turn out to be caused by a specific agent, "regimens that may be more strongly associated with increased cognitive changes could be avoided," Dr. Ganz states.

Earlier this year, Shelli R. Kesler, PhD, from Stanford University School of Medicine in California, and colleagues published a study in a the Archives of Neurology that also found changes in brain activity after chemotherapy for breast cancer.

As reported by Medscape Medical News, Dr. Kesler and her team used functional magnetic resonance imaging to assess prefrontal executive function in breast cancer survivors who had undergone chemotherapy, in survivors who had not, and in healthy women with no history of breast cancer.

Dr. Kesler and colleagues found that women who received chemotherapy showed significantly reduced left caudal lateral prefrontal cortex activation and reduced processing speed compared with the other women, and that this reduced activation correlated with self-reported executive dysfunction.

At the time, Dr. Kesler told Medscape Medical News she hoped her study validates the experience of breast cancer survivors treated with chemotherapy.

"Physicians sometimes tell them that they are just imagining the problem. Our study shows that there really is a problem. It's not just stress. It's not their imagination. It's a real brain change."

Dr. Deprez and Dr. Kesler have disclosed no relevant financial relationships. Dr. Ganz acknowledges that her editorial was supported by funding from the Breast Cancer Research Foundation and the National Cancer Institute.

J Clin Oncol. Published online December 19, 2011. Abstract, Editorial

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