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DNA in Predicting Response After Systemic Therapy in Women With Metastatic Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00899548
Recruitment Status : Completed
First Posted : May 12, 2009
Results First Posted : July 26, 2019
Last Update Posted : July 26, 2019
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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.

Condition or disease Intervention/treatment
Breast Cancer Genetic: DNA methylation analysis Genetic: microarray analysis Genetic: polymerase chain reaction Other: laboratory biomarker analysis

Detailed Description:



  • 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.


  • 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.

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Study Type : Observational
Actual Enrollment : 182 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: DNA Methylation in Serum as a Predictive Marker of Progression and Survival Following Systemic Therapy in Patients With Metastatic Breast Cancer
Actual Study Start Date : January 2007
Actual Primary Completion Date : June 2010
Actual Study Completion Date : October 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Group/Cohort Intervention/treatment
Metastatic breast cancer patients
DNA methylation analysis, microarray analysis, polymerase chain reaction, laboratory biomarker analysis
Genetic: DNA methylation analysis
laboratory analysis

Genetic: microarray analysis
laboratory analysis

Genetic: polymerase chain reaction
laboratory analysis

Other: laboratory biomarker analysis
laboratory analysis

Primary Outcome Measures :
  1. 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 ]
  2. 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.

  3. Effects of Common Exposures (i.e., Alcohol, Smoking, Medications, and Dietary Factors) on Patterns of Serum Methylation [ Time Frame: 9-12 weeks ]
  4. Creation of a Predictive Model of DNA Methylation Profiles [ Time Frame: 9-12 weeks ]

Secondary Outcome Measures :
  1. Overall Survival in Patients With a High vs. Low CMI Value [ Time Frame: from week 4 to up to 3 years ]
  2. Correlation of CTCs With Serum Methylation [ Time Frame: 3-4 weeks ]

Other Outcome Measures:
  1. Determination if the Addition of CTCs to Serum Methylation Results in an Improved Predictive Model [ Time Frame: 3-4 weeks ]

Biospecimen Retention:   Samples With DNA
Serum, plasma, DNA, RNA, whole blood

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population
Metastatic breast cancer patients and women without a history of breast cancer (ie, healthy women or "normals')


  • Meets 1 of the following criteria:

    • Histologically and/or cytologically confirmed stage IV adenocarcinoma of the breast (patient)
    • No diagnosis of an abnormal breast biopsy (including atypical ductal or lobular hyperplasia), or new diagnosis of breast cancer or breast cancer recurrence within the past five years (healthy participant)
  • Evidence of disease progression AND initiating a new systemic treatment regimen with trastuzumab (Herceptin®), chemotherapy, endocrine therapy, or investigational agent(s) (patient)

    • Treatment may be given as a single agent or in combination
  • Measurable or evaluable disease (patient)

    • Measurable disease is defined as ≥ 1 measurable lesion identified by RECIST criteria
    • Patients with evaluable disease only must have ≥ 1 tumor marker (e.g., carcinoembryonic antigen, CA 27-29, or CA 15-3) above normal level
  • Treated brain metastases (surgery or radiation therapy) allowed provided patient has evidence of disease stability or presence of other site(s) of measurable or evaluable disease (patient)

    • No leptomeningeal disease
  • Hormone receptor status not specified


  • Female
  • Menopausal status not specified
  • ECOG performance status 0-2
  • No known cancer within the past 5 years other than basal cell or squamous cell carcinoma of the skin and/or adequately treated cervical cancer (healthy participant)
  • Not pregnant or nursing


  • See Disease Characteristics
  • Prior therapy in the preoperative, adjuvant, and/or metastatic setting allowed

    • Any number of prior regimens in any setting allowed
  • No prior radiation therapy to the only site of disease unless there is evidence of post-radiation disease progression
  • No selective estrogen receptor modulator or aromatase inhibitor for breast cancer prevention or therapy within the past 12 months (healthy participant)
  • Prior or concurrent use of raloxifene for osteopenia or osteoporosis therapy allowed (healthy participant)
  • Concurrent participation in another clinical trial, including one involving an investigational agent(s), allowed

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00899548

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United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202-5289
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, North Carolina
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7295
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
National Cancer Institute (NCI)
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Principal Investigator: Antonio C. Wolff, MD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Publications of Results:
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Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Identifier: NCT00899548    
Other Study ID Numbers: J0524
P30CA006973 ( U.S. NIH Grant/Contract )
JHOC-J0524 ( Other Identifier: SKCCC at Johns Hopkins )
JHOC-SKCCC-J0524 ( Other Identifier: SKCCC at Johns Hopkins )
CDR0000509417 ( Other Identifier: NCI PDQ )
NA_00000717 ( Other Identifier: JHM IRB )
First Posted: May 12, 2009    Key Record Dates
Results First Posted: July 26, 2019
Last Update Posted: July 26, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data set will be available upon review and approval by the Correlative Science Review Committee of the Translational Breast Cancer Research Consortium (TBCRC). Inquiries should be addressed to the study chair, Dr. Antonio Wolff
Time Frame: Not yet determined
Access Criteria: Not yet determined
Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
stage IV breast cancer
recurrent breast cancer
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases