Analysis of Prognostic and Predictive Genomic Signatures Using Archival Paraffin-embedded Tumor Specimens in Breast Cancer

January 21, 2014 updated by: National University Hospital, Singapore

Major Aims of study:

  1. To create a gene expression-based prognostic device that complements or exceeds the prognostic utility of conventional biomarkers of breast cancer outcome.
  2. To identify one or more clinical subgroups of patients for which the prognostic device outperforms, or substantially adds to, the prognostic performance of conventional markers that currently determine therapeutic strategies.

Sub-Aims of study:

  1. Assess the prognostic value of the multiple gene expression signatures, alone and in combination, using a large cohort of breast cancer patients for which pathology, treatment and outcome is available. A "training" and "testing" design is proposed.
  2. Evaluate the utility of a prognostic device that measures gene expression levels from formalin-fixed paraffin-embedded specimens (FFPEs) of primary resected tumors. The investigators will utilize the Affymetrix Quantigene 2.0 Assay and/or the Illumina BeadXpress VeraCode DASL Gene Expression Assay (FDA-approved IVDMIA.)
  3. For specific clinical subgroups of patients/tumors, the investigators will mathematically identify additive or synergistic prognostic relationships between genes and gene signatures that, in combination, will yield maximal risk prediction (distant metastases-free survival) for patients.
  4. Compare the prognostic utility of the investigators device to that of the conventional prognostic variables that are currently used to determine therapeutic strategy.
  5. Incorporate the prognostic signatures into a practical prognosis algorithm that seeks to include conventional measures of outcome such as tumor size, histologic grade, nodal status, patient age, or Nottingham index, etc.

The investigators hypothesize that adequate quality and quantity of tumor RNA may be extracted from archival paraffin-embedded tumor specimens for gene expression profiling, and that archival tumor-derived genomic signatures may be used as prognosticators or predictors in breast cancer.

Study Overview

Status

Unknown

Conditions

Detailed Description

800 breast cancer patients who fulfill the eligibiltiy criteria will be selected from the NUH breast cancer registry (400 for training, 400 for validation). Eligible patients should have at least 5 years' follow-up at NUH and have an available archival paraffin-embedded tumor block stored at the Department of Pathology, NUH. 8-10 ten-micron sections from each tumor block will be cut and RNA extracted from the sections. RNA will then be profiled using high-throughput gene expression platforms (Illumina Veracode assay, Affymetrix Quantigene assay). Raw gene expression data will be applied in the following signatures previously generated by the Genome Institute of Singapore:

  1. 32-gene p53 Pathway Signature
  2. 5-gene Genetic Grade Signature
  3. 33-gene TuM1 Signature
  4. 10-gene ER Signature (Miller & Tan, et. al., unpublished)
  5. 6-gene 3-Ratio Predictor (Miller & Karuturi, et. al., unpublished)
  6. 5-gene HER2 Amplicon Predictor (Miller & Karuturi, et. al., unpublished)
  7. 7-gene Basal-Luminal Discriminator (Miller, unpublished)

The prognostic and/or predictive abilities of these signatures will be compared with conventional clinical prognosticators and predictors with the goal of developing archival tumor-derived genomic tests for breast cancer management in the future.

The archival paraffin-embedded tumor blocks are left-over samples after clinical use. They are not samples that have been consented for research purpose. We are requesting for waiver of consent as this is a minimal risk study. We will ensure that sufficient tissue be left behind for future routine diagnostic purposes. Sections taken from each tumor will be coded with no patient identifiers to protect the privacy and confidentiality of the participants.

The results generated from the tumor samples in this study will not impact on the clinical management of the patients.

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
        • National University Hospital

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

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Non-Probability Sample

Study Population

800 breast cancer patients who fulfill the eligibility criteria will be selected from the NUH breast cancer registry (400 for training, 400 for validation).

Description

Inclusion Criteria:

- Eligible patients should have at least 5 years' follow-up at NUH and have an available archival paraffin-embedded tumor block stored at the Department of Pathology, NUH

Exclusion Criteria:

  • Non breast cancer patients

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?

Design Details

Cohorts and Interventions

Group / Cohort
Breast cancer patients

Collaborators and Investigators

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

Sponsor

National University Hospital, Singapore

Investigators

  • Principal Investigator: Soo Chin Lee, 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

September 1, 2010

Primary Completion (Anticipated)

December 1, 2014

Study Completion

December 1, 2014

Study Registration Dates

First Submitted

August 31, 2010

First Submitted That Met QC Criteria

November 22, 2010

First Posted (Estimate)

November 24, 2010

Study Record Updates

Last Update Posted (Estimate)

January 22, 2014

Last Update Submitted That Met QC Criteria

January 21, 2014

Last Verified

January 1, 2014

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BR05/22/10

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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