We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov
ClinicalTrials.gov Menu
IMPORTANT: Due to the lapse in government funding, the information on this web site may not be up to date, transactions submitted via the web site may not be processed, and the agency may not be able to respond to inquiries until appropriations are enacted. Updates regarding government operating status and resumption of normal operations can be found at opm.gov.

Analysis of Prognostic and Predictive Genomic Signatures Using Archival Paraffin-embedded Tumor Specimens in 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.
ClinicalTrials.gov Identifier: NCT01247480
Recruitment Status : Unknown
Verified January 2014 by National University Hospital, Singapore.
Recruitment status was:  Active, not recruiting
First Posted : November 24, 2010
Last Update Posted : January 22, 2014
Sponsor:
Information provided by:

Study Description
Brief Summary:

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.


Condition or disease
Breast Tumor

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 Design

Study Type : Observational
Observational Model: Cohort
Time Perspective: Retrospective
Study Start Date : September 2010
Estimated Primary Completion Date : December 2014
Estimated Study Completion Date : December 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
U.S. FDA Resources

Groups and Cohorts

Group/Cohort
Breast cancer patients


Outcome Measures

Eligibility Criteria

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.


Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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).
Criteria

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
Contacts and Locations

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 ClinicalTrials.gov identifier (NCT number): NCT01247480


Locations
Singapore
National University Hospital
Singapore, Singapore
Sponsors and Collaborators
National University Hospital, Singapore
Investigators
Principal Investigator: Soo Chin Lee, MBBS, MRCP National University Hospital, Singapore