Neuroinflammation and Age-associated Brain Pathology: Two Potential Mechanisms of Cognitive Impairment in Breast Cancer

Study Overview
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Brief Summary
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This study will use a PET/MRI scanner and an investigational radioactive drug called [F-18]DPA-714 that measures inflammation in the brain, also called neuroinflammation, before chemotherapy and after 3 to 6 cycles of chemotherapy given as part of your clinical care. In addition, this study will use a PET/MRI scanner with an investigational radioactive drug called [C-11]PiB that measures the amount of abnormal protein (called beta-amyloid) in the brain that is a marker of Alzheimer's disease pathology. One of the most common complaints among breast cancer survivors is cognitive or memory problems especially in older adults. Researchers need to better understand the mechanisms and risk factors for cognitive problems in order to address this problem. This study seeks to examine two mechanisms, neuroinflammation and amyloid deposition, that have been suggested in other age-related cognitive disorders. This study may help physicians and researchers develop new treatments to protect the brain in cancer patients. UAB plans to enroll 20 participants in this study.

Official Title
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Neuroinflammation and Age-associated Brain Pathology: Two Potential Mechanisms of Cognitive Impairment in Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: [11C]PiB and 18F-labeled DPA-714 PET scan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 50 years of age or older Female gender Newly diagnosed treatment naïve women with breast cancer that meet the following criteria: Stage IIA: Any 1 of these conditions: There is no evidence of a tumor in the breast, but the cancer has spread to 1 to 3 axillary lymph nodes. It has no spread to distant parts of the body. (T0, N1, M0). The tumor is 20mm or smaller and has spread to the axillary lymph nodes (T1, N1, M0). The tumor is larger then 20mm but not larger than 50mm and has not spread to the axillary lymph nodes (T2, N1, M0). Stage IIB: Either of these conditions: The tumor is larger than 20mm but not larger then 50mm and had spread to 1 to 3 axillary lymph nodes (T2, N1, M0). The tumor is larger than 50mm but has not spread to the axillary lymph nodes (T3, N0, M0). StageIIIA: 1.The cancer of any size has spread to 4 to 9 axillary lymph nodes or to internal mammary lymph nodes. It has not spread to other parts of the body (T0, T1, T2, N2, M0). Stage IIIA may also be a tumor larger than 50mm that has spread to 1 to 3 axillary lymph nodes (T3, N1, M0). 4. High or mixed affinity binder for TSPO ligands based on genotyping for single nucleotide polymorphism (SNP) rs6971. 5. English is primary language 6. Planned neoadjuvant chemotherapy with either a taxane or an anthracycline drug Exclusion Criteria: Contraindication to PET/MRI, including claustrophobia Pregnancy Lactation Individuals who are unable to participate in the imaging portion due to severity of their medical condition Chronic infectious disease (e.g. HIV, HCV) Chronic inflammatory disease (e.g., fibromyalgia, MS, etc) or autoimmune disease Viral or bacterial illness requiring medical attention and/or antibiotics within 1 month of study participation Blood or blood clotting disorder Cancer that has metastasized to the brain Positive urine β-hCG test day of procedure or a serum hCG test within 48 hours prior to the administration of [18F]DPA-714 and [11C]PiB. Currently enrolled in a clinical trial utilizing experimental therapies. Low affinity binder for TSPO ligands based on genotyping for SNP rs6971. Prior brain tumor or other neurological condition known to affect cognition A diagnosis of dementia unrelated to cancer or an adjusted MMSE score < 24

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Women with stage 1-4 newly diagnosed breast cancer<br> | Drug: [11C]PiB and 18F-labeled DPA-714 PET scan<br>* One PET with [11C]PiB and One PET with [18F]DPA-714 before chemotherapy treatment begins. One more PET with [18F]DPA-714 after completion of 3-6 cycles of chemotherapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure neuroinflammation by calculating the concentration and regional distribution of activated brain microglia/macrophages using PET ligand [F-18]DPA-714. |  | Pre-study visit through 3-6 cycles of chemotherapy (each cycle is typically 2 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlate cognitive testing and self-reporting before and after beginning cancer therapy with the concentration and regional brain distribution of pathologic amyloid deposition measured with the PET tracer [C-11]PiB prior to beginning therapy. | Cognitive testing: Hopkins Verbal Learning Test-Revised (HVLT-R), 10/36 Spatial Recall Test Trail Making Test Part A, PASAT Controlled Oral Word Association Test (COWAT) Trail Making Test Part B and the Night Out Task (NOT) Self-report measures: Compensation Strategy Questionnaire (Ecomp) Cognitive Failures Questionnaire HADS Distress Thermometer FACT | After pre-study visit and before starting chemotherapy |