Tissue Microarrays Available for Investigations of Prognostic Breast Cancer Biomarkers

Notice Number: NOT-CA-09-004

Key Dates
Release Date: October 24, 2008

Issued by
National Cancer Institute (NCI) (http://www.cancer.gov/)

The Cooperative Breast Cancer Tissue Resource (CBCTR) of the National Cancer Institute (NCI) announces the availability of tissue microarrays of formalin-fixed, paraffin-embedded human tumor specimens annotated with pathologic and clinical outcome information. These arrays are designed to provide high statistical power to detect associations of biomarker expression with disease recurrence or survival outcomes in stage I breast cancer.

The evaluation of prognostic and predictive biomarkers for breast cancer requires access to human tumor tissue specimens with appropriate clinical and pathologic annotations.  Promising results from discovery efforts must be confirmed in independent case sets large enough to provide adequate statistical power to detect biologically or clinically meaningful biomarker effects.  Assays intended for use in routine clinical practice must be tested on formalin-fixed, paraffin-embedded tissue samples procured from multiple institutions.  The association of laboratory results with clinical outcomes requires specimens from cases that are annotated with detailed and reliable follow-up information about disease recurrence and survival.

To meet this need, the NCI created the CBCTR in 1994.  The CBCTR currently has more than 9000 specimens of invasive and non-invasive breast cancer in storage at four geographically dispersed institutions in the United States, with the majority of the specimens having been obtained from patients diagnosed from 1974 through 1997.  Patients received treatment in the community, usually not on clinical trial protocols.  All cases in this resource have been reviewed by CBCTR-affiliated pathologists, in accordance with a standardized pathology manual; a common set of clinical and follow-up information has been gathered from tumor registries and other local sources, for deposit into a central database.  Outcome information continues to be updated, so that the length of follow-up for many cases now exceeds 10 years.

Tissue microarrays (TMAs) provide a means to assemble useful sets of specimens in an extremely efficient format for use with assays suitable for formalin-fixed paraffin-embedded tissues.  Since 2001, the CBCTR has made available TMAs that permit comparisons of biomarker expression across disease stages (i.e., node-negative, node-positive, and metastatic disease) of breast cancer.  While useful for determining the prevalence of a biomarker and its association with stage, these previously available TMAs were not designed for evaluation of associations between markers and disease recurrence or survival.

The CBCTR has now developed a new TMA that is designed to allow investigators to identify and examine potential prognostic markers in non-metastatic breast cancer.  Separate TMAs will be constructed for each of the three non-metastatic TNM (tumor, nodes, and metastases) stages, I-III (as defined by American Joint Committee on Cancer: AJCC Manual for Staging of Cancer, 5th edition, Fleming ID, Cooper JS, Murphy GP, Sullivan BO, Sobin LH, Yarbro JW, et al., Philadelphia, PA, USA: Lippincott-Raven, 1997).  The Stage I TMA is currently available (CBCTR 2008 Series Stage I Prognostic TMA), and the Stage II and III TMAs are anticipated to be available within the next year.

The CBCTR 2008 Series Stage I Prognostic TMA represents a collection of 590 stage I invasive breast cancer tissue specimens with associated clinico-pathologic data and clinical follow-up information.  Control specimens include normal breast and fibroadenoma tissue, non-breast tissues, and breast cancer cell lines.  Cases are annotated with both demographic and pathology data, as well as with limited information on the basic treatment received (e.g., chemotherapy, radiation therapy, hormonal therapy).  Clinical endpoints are overall survival and recurrence-free survival. The sample size was determined such that it would provide approximately 80% or greater power in the subgroup of ductal cancers to detect a hazard ratio of 2.0 for overall survival associated with a binary biomarker that has prevalence between 20% and 80%.  For marker prevalence between 30% and 70%, the power is greater than 90%.

Any investigator studying promising breast cancer biomarkers can request access to either of these TMAs.  For details on request submission, please see http://www.cbctr.nci.nih.gov/applic.html.  For further information about this program, please visit http://www.cbctr.nci.nih.gov.


For questions or further information about this Notice, contact:

Tracy G. Lively, Ph.D.
Diagnostics Evaluation Branch
Cancer Diagnosis Program
National Cancer Institute, NIH
6130 Executive Boulevard, Room 6042, MSC 7420
Bethesda, MD 20892-7420 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: 301-496-1591
Fax: 301-402-7819
E-mail: livelyt@mail.nih.gov

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