Cognitive complaints have been anecdotally reported among women receiving adjuvant chemotherapy for breast cancer, and recently this has been subjected to more rigorous study. Cerebral functioning can be assessed by self-report, standardized neuropsychological testing, and through examination of brain metabolism (all of which have been studied in our laboratory). The literature suggests a relationship between chemotherapy exposure and poorer performance on neurocognitive testing; however, patients with cognitive complaints do not necessarily test poorly and their complaints are often associated with symptoms of depression and anxiety. Preliminary work in our laboratory suggests that hormonal changes associated with menopause and adjuvant endocrine therapy for breast cancer also influence the effects of chemotherapy on cognitive functioning. Little is known about the potential mechanisms by which adjuvant endocrine therapy influences cerebral functioning after breast cancer treatment, and in this study we will address this question by studying women who have recently completed their primary breast cancer treatments (surgery, radiation, chemotherapy) and who are about to initiate adjuvant endocrine therapy (with tamoxifen or aromatase inhibitors). We will examine the potential mechanisms by which endocrine therapy affects cerebral functioning, by consideration of a comprehensive framework that includes the role of constitutional symptoms (fatigue, depression, anxiety), and immune alterations, in addition to specific cancer treatments (chemotherapy, hormonal treatments), and endogenous endocrine exposures (estrogen, cortisol). In this longitudinal, observational cohort study, we propose the following specific aims: 1)To evaluate the effects of adjuvant endocrine therapy on cognitive functioning through standardized questionnaires and neuropsychological assessments in 260 breast cancer patients at the end of primary treatment (baseline) when endocrine treatment is initiated, and one year later (follow-up). 2)To examine the association between cognitive functioning and measures of cerebral metabolism by obtaining positron emission tomography (PET) brain imaging, at rest and with a memory challenge, in close temporal proximity to the baseline assessment of cognitive functioning in a subset of 60 women, with a follow-up assessment one year later. 3)To explore the biopsychosocial mechanisms by which adjuvant endocrine therapy influences cerebral functioning by examining changes in cognitive functioning and brain metabolism, and their relationship to immune and endocrine function, mood and symptoms between the baseline and follow-up assessment one year later. Lay summary: Breast cancer is the most common cancer in women. After treatments for breast cancer, some women complain of difficulty in concentrating and thinking. This study will examine the effects of breast cancer treatments on cognitive, psychological, immune and endocrine function to try to understand the biological mechanisms of these complaints so that they may be better prevented or treated in the future. ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA109650-03
Application #
7469506
Study Section
Behavioral Medicine, Interventions and Outcomes Study Section (BMIO)
Program Officer
Mc Donald, Paige A
Project Start
2006-09-14
Project End
2011-07-31
Budget Start
2008-08-01
Budget End
2009-07-31
Support Year
3
Fiscal Year
2008
Total Cost
$464,969
Indirect Cost
Name
University of California Los Angeles
Department
Internal Medicine/Medicine
Type
Schools of Public Health
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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Van Dyk, Kathleen; Bower, Julienne E; Crespi, Catherine M et al. (2018) Cognitive function following breast cancer treatment and associations with concurrent symptoms. NPJ Breast Cancer 4:25
Van Dyk, Kathleen; Crespi, Catherine M; Bower, Julienne E et al. (2018) The cognitive effects of endocrine therapy in survivors of breast cancer: A prospective longitudinal study up to 6 years after treatment. Cancer :
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Boyle, Chloe C; Ganz, Patricia A; Van Dyk, Kathleen M et al. (2017) Inflammation and attentional bias in breast cancer survivors. Brain Behav Immun 66:85-88
Van Dyk, Kathleen; Ganz, Patricia A; Ercoli, Linda et al. (2016) Measuring cognitive complaints in breast cancer survivors: psychometric properties of the patient's assessment of own functioning inventory. Support Care Cancer 24:4939-4949
Ganz, Patricia A; Petersen, Laura; Bower, Julienne E et al. (2016) Impact of Adjuvant Endocrine Therapy on Quality of Life and Symptoms: Observational Data Over 12 Months From the Mind-Body Study. J Clin Oncol 34:816-24
Dooley, Larissa N; Ganz, Patricia A; Cole, Steve W et al. (2016) Val66Met BDNF polymorphism as a vulnerability factor for inflammation-associated depressive symptoms in women with breast cancer. J Affect Disord 197:43-50
Moreno, Patricia I; Moskowitz, Andrew L; Ganz, Patricia A et al. (2016) Positive Affect and Inflammatory Activity in Breast Cancer Survivors: Examining the Role of Affective Arousal. Psychosom Med 78:532-41

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