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Brain Structure and Function Differences in Monozygotic Twins: Possible Effects of Breast Cancer Chemotherapy

Robert J. Ferguson, Brenna C. McDonald, Andrew J. Saykin, Tim A. Ahles

From the Department of Rehabilitation Medicine, Eastern Maine Medical Center, Bangor, ME; Center for Neuroimaging, Department of Radiology, Indiana University School of Medicine, Indianapolis, IN; and the Department of Psychiatry and Behavioral Sciences and Neurocognitive Research Laboratory, Memorial Sloan-Kettering Cancer Center, New York, NY

Address reprint requests to Robert J. Ferguson, PhD, Maine Outpatient Rehabilitation Center, Eastern Maine Medical Center, 905 Union St, Bangor, ME 04401; e-mail: rferguson{at}emh.org

Purpose: Adjuvant chemotherapy has been associated with mild cognitive decline among a subset of breast cancer survivors. Late cognitive effects after chemotherapy can have a deleterious impact on survivor quality of life and functional health; however, the etiology of chemotherapy-related cognitive dysfunction remains unknown.

Patients and Methods: We present a case of monozygotic twins who are discordant for breast cancer and chemotherapy exposure (ie, one twin contracted breast cancer and underwent chemotherapy, and the other had no breast cancer). As part of a larger study, each was evaluated with standardized, self-report measures of cognitive function, standard neuropsychological tests, and structural and functional magnetic resonance imaging (MRI).

Results: Results indicated small differences in neuropsychological test performance but striking contrasts in self-reported cognitive complaints and structural and functional MRI images. Specifically, the twin who underwent chemotherapy had substantially more subjective cognitive complaints, more white matter hyperintensities on MRI, and an expanded spatial extent of brain activation during working memory processing than her nonaffected twin.

Conclusion: This case illustrates possible physiologic mechanisms that could produce long-term cognitive complaints among chemotherapy recipients and help formulate hypotheses for further empirical study in the area of chemotherapy-associated cognitive dysfunction.

Supported by grants from the Office of Cancer Survivorship, National Cancer Institute; Grants No. R01 CA101318, R03 CA90151, and R01 CA87845 from the National Institutes of Health; and the Lance Armstrong Foundation.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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