Prefrontal Cortex and Executive Function Impairments in Primary Breast Cancer

Prefrontal Cortex and Executive Function Impairments in Primary Breast Cancer
http://archneur.ama-assn.org/cgi/content/abstract/68/11/1447

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

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.

Author Affiliations: Stanford Cancer Center, Palo Alto (Dr Kesler), and Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford (Drs Kesler and O'Hara and Ms Kent), California.