Brain structure and function differences in monozygotic twins: possible effects of breast cancer chemotherapy

Abstract

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.

Fig 1

Fluid attenuated inversion recovery magnetic resonance images of white matter hyperintensities. The hyperintensities were read by the study neuroradiologist as of uncertain clinical significance, but they appeared somewhat more prominent throughout white matter in (A) the chemotherapy-treated twin than in (B) the twin who did not receive chemotherapy as confirmed by volumetric analysis.

Fig 2

Functional magnetic resonance images of 60-year-old identical twins during a working memory task with incrementally increasing levels of difficulty (left to right). Colored regions denote increased brain activation during working memory relative to a simple vigilance task. (A) Twin treated with chemotherapy; (B) twin who did not receive chemotherapy. Note the expanded spatial extent of cortical activation in the chemotherapy-treated twin.