Illuminating Breast Cancer Recurrence Risk  |   > Search     |   Take me to: Oncotype - Home Patients and Caregivers - Home Oncotype DX Logistics - Home About Oncotype DX The Role of Oncotype DX Oncotype DX Studies Oncotype DX Logistics Clinical Practice Guidelines Health Insurance Coverage The TAILORx Clinical Trial Frequently Asked Questions About Oncotype DX Oncotype DX Process Advantages of RT-PCR Oncotype DX Development Oncotype DX Results The Role of Oncotype DX Oncotype DX Studies Oncotype DX Logistics Clinical Practice Guidelines Health Insurance Coverage The TAILORx Clinical Trial Frequently Asked Questions Oncotype DX Development The Oncotype DX® assay was developed in four steps: 1. Optimization of methods for quantifying gene expression in formalin-fixed, paraffin-embedded tissue (FPET) 2. Selection of 250 candidate genes from the human genome 3. Testing of candidate genes to identify an optimal gene panel for clinical validation 4. Prospective clinical validation of the 21-gene panel and Recurrence Score® calculation Step 1. Optimization of methods for quantifying gene expression in formalin-fixed, paraffin-embedded tissue The ability to work with FPET samples is critical in the US, as this is the standard method for tumor preservation and storage. When tissue is preserved in paraffin, the RNA is fragmented. However, the relative ratio of RNA between genes is unchanged. By utilizing RT-PCR (reverse transcriptase-polymerase chain reaction) techniques, the expression of any gene — relative to a set of reference genes — can be measured. To develop the Oncotype DX assay, Genomic Health® researchers optimized RT-PCR technology for high-throughput, real-time quantitation of specific RNA in FPET and to be reproducible regardless of the variability inherent in tumor blocks. To learn more about RT-PCR, click here. [ back to top ] Step 2. Selection of 250 candidate genes from the human genome Genomic Health researchers relied on numerous sources to identify 250 candidate genes — those possibly associated with breast cancer tumor behavior — from among the approximately 25,000 genes in the human genome. [ back to top ] Step 3. Testing of candidate genes to identify an optimal gene panel for clinical validation The 250 candidate genes were analyzed in a total of 447 patients from three independent clinical studies in order to identify a panel of genes strongly correlated with distant recurrence-free survival. The selection of the 16 cancer genes used for the Oncotype DX assay was based on the results of the three clinical trials, which demonstrated a consistent and strong statistical link between these genes and distant breast cancer recurrence. Five reference genes were identified to normalize the expression of these cancer-related genes. In addition, these studies were the basis for the Recurrence Score calculation, which combines the gene expression data from this gene panel into a single result. Click here to review the key abstracts. [ back to top ] Step 4. Prospective clinical validation of the 21-gene panel and Recurrence Score calculation The Oncotype DX gene panel and Recurrence Score calculation were validated in a large, independent, multicenter clinical trial (NSABP Study B-14) and in a large population-based case-control study in breast cancer patients at Northern California Kaiser Permanente. The endpoints and analysis plan were prospectively defined. The results of these studies were included in the Best of Oncology session at ASCO 2004 and the results of the NSABP B-14 clinical validation study were published in The New England Journal of Medicine (December 30, 2004). [ back to top ] References: Paik S, Shak S, Tang G, et al. A Multigene Assay to Predict Recurrence of Tamoxifen-Treated, Node-Negative Breast Cancer. New England Journal of Medicine. 2004;351(27). Esteban J, Baker J, Cronin M, et al. Tumor gene expression and prognosis in breast cancer: multi-gene RT-PCR assay of paraffin-embedded tissue. Presented at: Thirty-ninth Meeting of the American Society of Clinical Oncology. May 31-June 3, 2003; Chicago, IL. Abstract #3416. Cobleigh MA, Bitterman P, Baker J, et al. Tumor gene expression predicts distant disease-free survival (DDFS) in breast cancer patients with 10 or more positive nodes: high throughput RT-PCR assay of paraffin-embedded tumor tissues. Presented at: Thirty-ninth Meeting of the American Society of Clinical Oncology. May 31-June 3, 2003; Chicago, IL. Abstract #3415. [ back to top ] What's New? August 5, 2008 Genomic Health Announces Second Quarter 2008 Financial Results and Business Progress July 29, 2008 Genomic Health to Announce Second Quarter 2008 Financial Results and Host Conference Call on Tuesday, August 5, 2008

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