Pre-analytical Factors Affecting ctDNA Analysis in Early and Locally Advanced Breast Cancer

Study Overview
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Brief Summary
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This study evaluates pre-analytical factors affecting circulating tumor deoxyribonucleic acid (ctDNA) analysis in breast cancer that not spread beyond the breast and or lymph nodes (early and locally advanced). ctDNA refers to freely circulating tumor DNA fragments found in the blood plasma. Pre-analytical factors such as blood collection tubes, delays in separation of plasma, centrifugation speeds, storage conditions, shipping and DNA extraction methods can all affect ctDNA measurements. Inappropriate processing can cause breaking down of the membrane (lysis) of peripheral blood cells that release background wild-type DNA and may also cause degradation of circulating tumor-specific DNA fragments. Both mechanisms will dilute levels of ctDNA in plasma and make it more difficult to detect. Evaluating the pre-analytical factors of the collection of blood and left over tissue samples for the research of cancer may help researchers to evaluate the impact of the blood collection/processing and long-term storage from patients with locally advanced breast cancer.

Detailed Description
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PRIMARY OBJECTIVES: I. To evaluate the impact of blood collection/processing. II. To evaluate the impact of long-term storage of plasma and extracted DNA. OUTLINE: This is an observational study. Patients undergo blood sample collection throughout the study. Patients also undergo collection of leftover tissue samples from standard of care (SOC) procedures and have medical records reviewed.

Official Title
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Pre-Analytical Factors Affecting ctDNA Analysis in Early and Locally Advanced Breast Cancer

Conditions
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Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8, Early Stage Breast Carcinoma, Locally Advanced Breast Carcinoma

Intervention / Treatment
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* Procedure: Biospecimen Collection
* Other: Electronic Health Record Review


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All women > 18 years of age Stage I-III breast cancer Subject has consented to IRB 2130-00 Tissue Registry Exclusion Criteria: Stage IV breast cancer Unwilling or unable to give consent Unable to participate for 1 year No one with a concurrent cancer except those diagnosed with an in situ cancer or non-melanoma skin cancer

Ages Eligible for Study
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Minimum Age: 18 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Observational (Biospecimen collection, medical record)<br>Patients undergo blood sample collection throughout the study. Patients also undergo collection of leftover tissue samples from SOC procedures and have medical records reviewed. | Procedure: Biospecimen Collection<br>* Undergo blood and leftover tissue sample collection<br>* Other names: Specimen Collection;Other: Electronic Health Record Review<br>* Medical records are reviewed<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in tumor specific circulating tumor deoxyribonucleic acid (ctDNA) levels | Will be measured as tumor fraction (%), using TARgeted DIgital Sequencing (TARDIS). | Baseline to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in total cell-free DNA concentration | Will be measured in genome copies/ml of plasma, using the Quality Assessment (QA) assay. | Baseline to 5 years | 
| Change in total cell-free DNA fragment size profile | Will be measured as % fragmented, using the Quality Assessment (QA) assay. | Baseline to 5 years | 
| Change in tumor-specific circulating tumor deoxyribonucleic acid (ctDNA) fragment size profile | Will be measured as average fragment size, using TARgeted DIgital Sequencing (TARDIS). | Baseline to 5 years | 
| Background error rate | Will be measured as errors per bp sequenced, measured using TARgeted DIgital Sequencing (TARDIS). | Baseline to 5 years |