Inflammation-Induced CNS Glutamate During Breast Cancer Treatment

Study Overview
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Brief Summary
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The purpose of this study is to try and provide data linking the impact of increased inflammatory cytokines as a result of chemotherapy and their relationship with increased levels of CNS glutamate and related behavioral and cognitive consequences in breast cancer patients. The investigators will use neuropsychiatric assessments, blood sampling and Magnetic Resonance Spectroscopy (MRS) to collect study data.

Detailed Description
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Approximately 70% of women with breast cancer experience behavioral and/or cognitive symptoms during treatment with chemotherapy and approximately 30% of women continue to experience these symptoms months to years after treatment completion. There is mounting data to suggest that inflammation may be involved and indicate that chemotherapy-treated breast cancer patients exhibit higher inflammatory markers than non-chemotherapy-treated patients, and inflammatory markers including interleukin (IL)-6 and soluble tumor necrosis factor (sTNFR2) have been associated with chemotherapy-induced depression and fatigue.

Official Title
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Inflammation-Induced CNS Glutamate During Breast Cancer Treatment

Conditions
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Breast Cancer

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female breast cancer patients will have undergone surgery (lumpectomy or mastectomy) with or without neoadjuvant or adjuvant chemotherapy Age between 21-65 years Exclusion Criteria: Taking trastuzumab

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Chemotherapy-treated breast cancer group<br>Female subjects with Stage I-III breast cancer treated with chemotherapy will complete the neuropsychiatric assessment battery, blood sampling, self-report forms and magnetic resonance spectroscopy (MRS) scans | |
| Non-Chemotherapy-treated breast cancer group<br>Non-chemotherapy treated female subjects with Stage I-III breast cancer will complete the neuropsychiatric assessment battery, blood sampling, self-report forms and magnetic resonance spectroscopy (MRS) scans | |
| Control group<br>Age and race-matched healthy women will complete the neuropsychiatric assessment battery, blood sampling, self-report forms and magnetic resonance spectroscopy (MRS) scans | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio of Glutamate to Creatine | Single voxel MRS (Magnetic Resonance Spectroscopy) scans will be done to determine the glutamate levels in the dACC (dorsal anterior cingulate cortex), basal ganglia and hippocampus and the glutamate/ creatine (Glu/Cr) ratio will be calculated.MRS utilizes a magnetic field to look at magnetic nuclei, which absorb and re-emit electromagnetic energy in the presence of the magnetic field. By looking at the peaks in the resultant spectra the structure and concentration of metabolites can be determined. | Baseline | 
| Levels of peripheral blood markers of inflammation | Peripheral blood samples will be analyzed for levels of plasma c-reactive protein (CRP), tumor necrosis factor (TNF) and its soluble receptors (sTNFR1 and 2), interleukin (IL)-1 beta and the IL-1 receptor antagonist, and IL-6 and its soluble receptor (sIL-6R). | Baseline | 
| Cognitive dysfunction | Cognitive measures of processing speed, attention, executive function, memory and motivation will be assessed. | Baseline | 
| Behavioral assessments | Behavioral assessments will be done to assessed to measure depression and anxiety. | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cognitive dysfunction, Inflammation, Fatigue, Decreased motivation