DNA Methylation in Serum as a Predictive Marker of Progression and Survival Following Systemic Therapy in Patients With Metastatic Breast Cancer
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Breast Cancer
- Sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
- Enrollment
- 182
- Locations
- 4
- Primary Endpoint
- Effects of Common Exposures (i.e., Alcohol, Smoking, Medications, and Dietary Factors) on Patterns of Serum Methylation
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
RATIONALE: Studying samples of blood from patients with cancer and from healthy participants in the laboratory may help doctors learn more about changes that may occur in DNA and identify biomarkers related to cancer. It may also help doctors predict how well patients will respond to systemic therapy.
PURPOSE: This laboratory study is looking at DNA in predicting response after systemic therapy in women with metastatic breast cancer.
Detailed Description
OBJECTIVES: Primary * Identify a panel of methylated gene markers in serum from women with metastatic breast cancer that is significantly different from that observed in healthy participants. * Assess changes in a panel of methylated gene markers from baseline, after 3-4 weeks, and after 9-12 weeks of systemic therapy in patients with metastatic breast cancer. * Determine the potential effects of common exposures (i.e., alcohol, smoking, medications, and dietary factors) on patterns of serum methylation in patients with metastatic breast cancer and in healthy participants. * Develop a predictive model using DNA methylation profiles in serum that predicts clinical outcome for an individual patient with metastatic disease. Secondary * Correlate circulating tumor cells (CTCs) with clinical outcome in patients with metastatic breast cancer. * Correlate CTCs with serum methylation in these patients. * Determine if the addition of CTCs to serum methylation results in an improved predictive model. OUTLINE: This is a prospective, multicenter study. Patients and healthy participants fill out health assessment questionnaires at baseline, week 3-4, and week 9-12. Patients undergo blood collection for methylated marker analysis at baseline, weeks 3-4, and weeks 9-12 and circulating tumor cell levels at baseline and weeks 3-4. Healthy participants undergo blood collection for methylated marker analysis at baseline. An additional cohort of healthy participants undergo follow-up blood collection ≥ 1 week after baseline. DNA methylation is measured by quantitative multiplex methylation-specific polymerase chain reaction (QM-MSP) assay. After completion of study procedures, patients are followed every 3-4 months. PROJECTED ACCRUAL: A total of 150 patients and 150 healthy participants will be accrued for this study.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Effects of Common Exposures (i.e., Alcohol, Smoking, Medications, and Dietary Factors) on Patterns of Serum Methylation
Time Frame: 9-12 weeks
Changes in Methylated Gene Markers as Measured by Cumulative Methylation Index
Time Frame: baseline, week 4
log change in cumulative methylation index (CMI) from baseline to week 4. Individual gene methylation (M) is calculated as a methylation index (MI) where MI = (methylated copies)/(number of methylated genes + gene standard copies) \* 100. The MI of each sample was averaged across duplicates. The cumulative methylation index (CMI) is the sum of the MI for all genes. The log change from based line to week 4 could increase or decrease. CMI was evaluated as a continuous marker for change from baseline.
Progression-free Survival in Patients With a High vs. Low Cumulative Methylation Index (CMI) Value
Time Frame: from week 4 to up to 87 months
Creation of a Predictive Model of DNA Methylation Profiles
Time Frame: 9-12 weeks
Secondary Outcomes
- Overall Survival in Patients With a High vs. Low CMI Value(from week 4 to up to 3 years)
- Correlation of CTCs With Serum Methylation(3-4 weeks)