Prefrontal cortex and executive function impairments in primary breast cancer.

Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Rd, MC5795, Stanford, CA 94305-5795, USA.
Archives of neurology (Impact Factor: 7.01). 11/2011; 68(11):1447-53. DOI: 10.1001/archneurol.2011.245
Source: PubMed

ABSTRACT 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.
Observational study.
University-based research facility.
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.
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.
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.


Available from: Shelli R Kesler, Jun 11, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Breast cancer and its treatments are associated with mild cognitive impairment and brain changes that could indicate an altered or accelerated brain aging process. We applied diffusion tensor imaging and graph theory to measure white matter organization and connectivity in 34 breast cancer survivors compared with 36 matched healthy female controls. We also investigated how brain networks (connectomes) in each group responded to simulated neurodegeneration based on network attack analysis. Compared with controls, the breast cancer group demonstrated significantly lower fractional anisotropy, altered small-world connectome properties, lower brain network tolerance to systematic region (node), and connection (edge) attacks and significant cognitive impairment. Lower tolerance to network attack was associated with cognitive impairment in the breast cancer group. These findings provide further evidence of diffuse white matter pathology after breast cancer and extend the literature in this area with unique data demonstrating increased vulnerability of the post-breast cancer brain network to future neurodegenerative processes. Copyright © 2015 Elsevier Inc. All rights reserved.
    Neurobiology of aging 05/2015; 36:2429-2442. DOI:10.1016/j.neurobiolaging.2015.04.015 · 4.85 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective Although regular physical activity is associated with lower all-cause and disease-specific mortality among breast cancer survivors (BCS), most BCS do not meet its recommended guidelines. Attention function, a domain of cognition, is essential for daily tasks such as exercising, a form of planned physical activity. We tested the hypotheses that lower self-reported attention function in BCS would be associated with less exercise and higher body mass index (BMI) by comparing a group of 505 young BCS (45 years or younger at diagnosis and 3-8 years post-treatment) with 466 acquaintance controls (AC).Methods The groups were compared on self-reported physical and psychological outcomes. Mplus software was used to perform confirmatory structural equation modeling with a robust maximum likelihood estimator to evaluate hypothesized relationships among variables. The criteria for good model fit were having root mean square error of approximation (RMSEA) < 0.06, comparative fit index (CFI) > 0.95, and standardized root mean square residual (SRMR) < 0.08. Modification indices were used to better fit the model.ResultsThe final model demonstrated good fit, with RMSEA = 0.05, CFI = 0.98, and SRMR = 0.03. After controlling for demographics, parameter estimates revealed that, compared with AC, young BCS reported worse attention function (p < 0.001), more depressive symptoms (p < 0.001), and more fatigue (p < 0.001). Controlling for fatigue, depression, and anxiety, better attention function was associated with a greater likelihood of exercise in the past 3 months (p = 0.039), which in turn was associated with a lower BMI (p < 0.001).Conclusions The significant association between attention function and physical activity, if confirmed in a longitudinal study, will provide new targets for interventions aimed at improving physical activity and decreasing BMI among BCS.
    Psycho-Oncology 03/2015; 24(3). DOI:10.1002/pon.3598 · 4.04 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Although adjuvant chemotherapy (CT) for breast cancer (BC) is associated with very late side-effects on cognition and brain function, studies on adverse effects of specific treatment regimens are scarce. Here, neurotoxicity profiles after different treatment strategies were compared in BC survivors randomized to high-dose (HI) or conventional-dose (CON-) CT, in women treated with radiotherapy (RT) -only and a healthy control (HC) group. We administered a neurocognitive test battery, a planning fMRI task (Tower of London) and episodic memory fMRI task (Paired Associates paradigm) in BC survivors who received CON-CT (n=24) and HC (n=27). Data were compared to BC survivors who received HI-CT (n=17) and RT-only (n=15) and who were previously assessed. Testing took place ±11.5 years post-CT. Furthermore, neurocognitive data were compared to neurocognitive data acquired ≤2 years post-treatment. Cognitive assessment revealed sustained cognitive decline in 10.5% of HI-CT, 8.3% of CON-CT, 6.7% of RT-only patients and 0% in the HC. Hypoactivation was found in task-related prefrontal and parietal areas for both CT-groups versus RT-only, with HI-CT showing more pronounced hypoactivation than CON-CT, combined with worse task performance. RT-only survivors performed at a similar level to HC while showing hyperactivation in task-related brain areas. Long after treatment, CT is associated with cognitive problems and task-related hypoactivation that depend on the specific cytotoxic regimen. This worse performance in patients who received CT could be explained by impaired brain functioning that is more severe with more intense CT
    Journal of the International Neuropsychological Society 12/2014; 21(01). DOI:10.1017/S1355617714001015 · 3.01 Impact Factor