Abstract

Some studies indicate that breast cancer (BC) survivors are at significant risk for long- term cognitive deficits. Increasing BC survival rates may thus result in a large and rapidly growing cohort of women with extended disease-related disability. Adjuvant chemotherapy may be a significant contributing factor to cognitive impairments in BC. However, the role of chemotherapy in BC cognitive outcome is controversial. The specific cognitive deficits in BC, their incidence and underlying mechanisms are largely unknown due to a paucity of research in this area. There currently are no treatments for cognitive deficits related to BC. The goals of the proposed research are to 1) define the specific cognitive deficits associated with BC and chemotherapy using comprehensive, ecologically valid neuropsychological assessment, 2) elucidate the neurobiologic states underlying cognitive impairments in women with BC using advanced neuroimaging techniques, 3) identify demographic, medical and genetic factors associated with cognitive outcome in BC and 4) test the efficacy of two innovative treatment methods - one for improving existing cognitive impairments and the other for preventing cognitive impairments. The proposed research will implement highly innovative methods including measurement of hippocampal neural stem cells, using neurofeedback as a preventative treatment method and evaluating a combination of genetic variants believed to influence cognitive outcome. Results of this project will provide prognostic information regarding and treatment options for cognitive effects of BC, will address the lack of treatment methods for cognitive impairments in general by providing a new model of cognitive rehabilitation, and will increase our understanding of neural injury, recovery and repair. Additionally, cancer in general affects millions of individuals - males and females of all age groups, socioeconomic strata and ethnicities. Therefore, results from this project may have broad applications by providing direction for studies of cognitive effects in other cancers and conditions treated with chemotherapy.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
NIH Director’s New Innovator Awards (DP2)
Project #
1DP2OD004445-01
Application #
7599478
Study Section
Special Emphasis Panel (ZGM1-NDIA-G (01))
Program Officer
Basavappa, Ravi
Project Start
2008-09-30
Project End
2013-06-30
Budget Start
2008-09-30
Budget End
2013-06-30
Support Year
1
Fiscal Year
2008
Total Cost
$2,400,000
Indirect Cost

  Institution

Name
Stanford University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305

  Publications

Hosseini, S M Hadi; Pritchard-Berman, Mika; Sosa, Natasha et al. (2016) Task-based neurofeedback training: A novel approach toward training executive functions. Neuroimage 134:153-159
Kesler, Shelli R; Blayney, Douglas W (2016) Neurotoxic Effects of Anthracycline- vs Nonanthracycline-Based Chemotherapy on Cognition in Breast Cancer Survivors. JAMA Oncol 2:185-92
Kesler, Shelli R; Watson, Christa L; Blayney, Douglas W (2015) Brain network alterations and vulnerability to simulated neurodegeneration in breast cancer. Neurobiol Aging 36:2429-42
Kesler, Shelli R (2014) Default mode network as a potential biomarker of chemotherapy-related brain injury. Neurobiol Aging 35 Suppl 2:S11-9
Hosseini, S M Hadi; Kesler, Shelli R (2014) Multivariate pattern analysis of FMRI in breast cancer survivors and healthy women. J Int Neuropsychol Soc 20:391-401
Garrett, Amy S; Lock, James; Datta, Nandini et al. (2014) Predicting clinical outcome using brain activation associated with set-shifting and central coherence skills in Anorexia Nervosa. J Psychiatr Res 57:26-33
Kesler, Shelli R; Wefel, Jeffrey S; Hosseini, S M Hadi et al. (2013) Default mode network connectivity distinguishes chemotherapy-treated breast cancer survivors from controls. Proc Natl Acad Sci U S A 110:11600-5
Kesler, Shelli R; Watson, Christa; Koovakkattu, Della et al. (2013) Elevated prefrontal myo-inositol and choline following breast cancer chemotherapy. Brain Imaging Behav 7:501-10
Hosseini, S M Hadi; Kesler, Shelli R (2013) Comparing connectivity pattern and small-world organization between structural correlation and resting-state networks in healthy adults. Neuroimage 78:402-14
Kesler, Shelli; Hadi Hosseini, S M; Heckler, Charles et al. (2013) Cognitive training for improving executive function in chemotherapy-treated breast cancer survivors. Clin Breast Cancer 13:299-306

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