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

21 Years
Open (Enrolling)
Breast Tumor Tissue

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Trial Information

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

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..

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

Type of Study:


Study Design:


Principal Investigator

Sing Huang Tan, MBBS, MRCP

Investigator Role:

Principal Investigator

Investigator Affiliation:

National University Hospital, Singapore


Singapore: Domain Specific Review Boards

Study ID:




Start Date:

October 2007

Completion Date:

Related Keywords:

  • Breast Tumor Tissue
  • Breast Neoplasms