Chemotherapy on Methylation Patterns in Breast Tumor Tissue Correlating With Clinical Response and Outcomes

June 15, 2008 updated by: National University Hospital, Singapore

Study of the Effect of Chemotherapy on Methylation Patterns in Breast Tumor Tissue and Paired Plasma Samples and Correlation With Clinical Response and Outcomes

Primary Objectives

  1. To identify hypermethylated genes in paired pretreatment breast tumor tissue and plasma samples from locally advanced and metastatic breast cancer patients using a known gene panel which includes APC1, Cyclin D2, RARB, RASSF1A, Twist, Hin1 and GSTP1.

    Rationale: We and others have determined the optimal panel of genes that are able to detect free DNA in plasma and serum. We will determine if the same panel of genes is effective for detecting tumor DNA in the plasma of locally advanced and metastatic breast cancer patients. Further, to determine if the methylation profile of the plasma DNA for these genes is the same or different from the primary tumor at presentation, we will analyze the primary tumor DNA from fresh frozen samples.

  2. To identify methylation pattern changes in the same subset of patients' plasma samples at 24 hours after completion of cycle 1 of chemotherapy and within 24 hours before cycle 2.

Rationale: The optimal timing of sampling for methylation analysis that is reflective of the tumors response to chemotherapy is not known. How soon methylation changes are observed, whether they are high within 24 hours, as that tumor responds to chemotherapy, or whether changes can be observed only some time after one cycle of chemotherapy will be studied. (3) To also identify methylation pattern changes in breast tumor tissue after one cycle of chemotherapy.

Rationale: To look for a correlation with plasma methylation patterns

Secondary Objectives

(1) To correlate our observed patterns of methylation pre- and post-treatment with clinical parameters such as clinical and/or radiological response and patient outcome.

Study Overview

Status

Unknown

Conditions

Detailed Description

In advanced breast cancer, it is often difficult to predict which patients will respond favorably to systemic therapy to decide on treatment duration or options while minimizing exposure to toxic effects. Our goal is to examine using locally advanced and metastatic breast cancer tumor tissue and plasma, the methylation profile patterns pre- and post chemotherapy of a panel of biomarkers most commonly expressed in breast cancer and correlate them with tumor response and patient outcome.

Our hypothesis is that DNA methylation pattern changes at baseline and early into a course of systemic therapy can predict disease response or progression as well as survival. In the long term, this could prove clinically useful in limiting exposure to ineffective regimens and allowing earlier identification of more effective systemic therapy.

Core biopsies of breast tumor tissue are taken at baseline and after cycle 1 of docetaxel/ketoconazole. Plasma samples are drawn at baseline, 24 hours after cycle 1 chemotherapy and 24 hours before cycle 2. Thirty patients' specimens (60 core biopsies and 90 plasma samples) will be utilized. Quantitative multiplex methylation-specific PCR will be used for analyses of several tumor suppressor genes including APC1, Cyclin D2, RARB, RASSF1A, Twist, Hin1 and GSTP1. From this data, we will identify a preliminary gene panel associated with breast cancer which undergoes the most changes in methylation following systemic therapy. Thirty paraffin-embedded healthy tissue samples from mastectomy specimens and blood samples from unaffected individuals will serve as normal controls.

This preliminary study can be used to determine the clinical utility of DNA methylation in breast tumor tissue and plasma as a predictive marker for response to chemotherapy and a prognostic marker for patient outcome. If a relationship is found, we can then further study if the change in methylation pattern has clinical utility in influencing therapeutic decision-making which may be further expanded to the adjuvant setting..

Study Type

Observational

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Singapore
      • Singapore, Singapore
        • Recruiting
        • National University Hospital
        • Contact:
        • Principal Investigator:
          • Sing Huang Tan, MBBS, MRCP

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

Inclusion Criteria:

We are not actively recruiting breast cancer patients but using stored biospy and plasma samples collected in the stated Clinical Trial (Phase II study of docetaxel combined with ketoconazole in the first-line treatment of locally advanced or metastatic breast cancer patients with measurable primary breast tumor) which was already IRB-approved

For the normal controls, inclusion criteria are:

  1. Any female adult patient above 21
  2. No current or past history of underlying malignancies

Exclusion Criteria:

For normal controls, exclusion criteria are:

(1) Past or current history of malignancies

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National University Hospital, Singapore

Investigators

  • Principal Investigator: Sing Huang Tan, MBBS, MRCP, National University Hospital, Singapore

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2007

Study Registration Dates

First Submitted

June 15, 2008

First Submitted That Met QC Criteria

June 15, 2008

First Posted (Estimate)

June 17, 2008

Study Record Updates

Last Update Posted (Estimate)

June 17, 2008

Last Update Submitted That Met QC Criteria

June 15, 2008

Last Verified

June 1, 2008

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BR04/19/07

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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