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Original Contributions |

Prefrontal Cortex and Executive Function Impairments in Primary Breast Cancer

Shelli R. Kesler, PhD; Jamie S. Kent, MA; Ruth O’Hara, PhD
Arch Neurol. 2011;68(11):1447-1453. doi:10.1001/archneurol.2011.245.
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Objectives To examine differences in prefrontal-executive function between breast cancer (BC) survivors with and without a history of chemotherapy treatment compared with healthy control women and to determine the associations between prefrontal cortex deficits and behavioral impairments, as well as certain demographic and disease variables.

Design Observational study.

Setting University-based research facility.

Participants Twenty-five women with BC who had received chemotherapy, 19 women with BC who had not received chemotherapy, and 18 healthy female controls, all matched for age and other demographic variables.

Results Women with BC demonstrated significantly reduced activation in the left middle dorsolateral prefrontal cortex and premotor cortex compared with healthy controls. The chemotherapy group also demonstrated significantly reduced left caudal lateral prefrontal cortex activation and increased perseverative errors and reduced processing speed compared with the other 2 groups. Reduced left caudal lateral prefrontal cortex activation was significantly correlated with higher disease severity and elevated subjective executive dysfunction in the chemotherapy-treated women. Older age and lower educational level were associated with increased executive function impairment in the chemotherapy group.

Conclusions These findings provide further evidence of neurological impairment associated with primary BC irrespective of treatment history. The left caudal lateral prefrontal region may be particularly vulnerable to the effects of chemotherapy and/or disease severity and may represent a novel biomarker of subjective executive dysfunction in chemotherapy-treated women. Furthermore, negative effects of chemotherapy on brain function may be exacerbated by such factors as increased age and lower educational level.

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Figure 1. Combined axial overlays of within-group statistical parametric mapping results indicating similar profiles of functional brain activation during an executive function task across the 3 groups. Regions of significant activation included the bilateral cerebellum, the basal ganglia, the parietal lobe, and the dorsolateral prefrontal cortex. Activation for control individuals is shown in red, for the no-chemotherapy group in yellow, and for the chemotherapy group in violet. The numbers above the sections indicate axial coordinate position. Color bars show t score. Height threshold: P < .05, extent = 50 voxels, corrected for multiple comparisons. Overlays were created using MRIcron software (http://www.cabiatl.com/mricro/mricron/index.html).

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Figure 2. Axial overlays of statistical parametric mapping results indicating regions of significant between-group difference in brain activation. Female survivors of breast cancer demonstrated significantly reduced activation, irrespective of treatment history, during an executive function task compared with age-matched healthy controls in the left middle dorsolateral prefrontal cortex (Brodmann area [BA] 10/46; Montreal Neurological Institute [MNI] coordinates, −28, 28, 16; F = 8.2; cluster size = 711) (A) and the left medial frontal cortex (BA 6; MNI coordinates, −16, 2, 52; F = 5.7; cluster size = 58) (B). The chemotherapy-treated group also showed significantly reduced activation in the left caudal lateral prefrontal cortex compared with controls and the no-chemotherapy group (BA 8; MNI coordinates, −26, 16, 52; F = 5.9; cluster size = 120). Crosshairs show peak cluster location. The number in red at the top right of each section is the axial coordinate position. L indicates left; A, anterior. Color bars show the F statistic. Height threshold: P < .05, extent = 50 voxels, corrected for multiple comparisons. Overlays were created using MRIcron software (http://www.cabiatl.com/mricro /mricron/index.html).

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