Genomic Health Announces Positive Results of First Clinical Outcomes Study for Biomarker Discovery Using Next Generation Sequencing at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium

SAN ANTONIO, Dec. 8, 2011 /PRNewswire/ -- Genomic Health, Inc. (Nasdaq: GHDX) today announced the presentation of the first-of-its-kind clinical outcomes study for biomarker discovery applying next generation sequencing (NGS) for whole transcriptome profiling of archival formalin-fixed paraffin embedded (FFPE) tumor specimens.  Results presented at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium demonstrate that a proprietary RNA-Seq method developed at the company is capable of identifying validated genes that previously had been discovered by RT-PCR, the technology used to develop the Oncotype DX® breast cancer test.  RNA-Seq refers to the use of high-throughput sequencing to identify which RNAs are expressed in a given sample and generate a quantitative gene expression profile by counting the number of RNA copies that match each gene or region of the genome.  The technology allows Genomic Health scientists to assay the entire genome simultaneously to discover regions of the genome that are turned on or off in disease.  From these changes, researchers are focused on predicting disease outcomes.  In addition to re-confirming the original 21 Oncotype DX genes originally identified by RT-PCR, this study also revealed more than 1,800 new biological relationships associated with breast cancer recurrence.

"This study marks an important milestone in the clinical application of next generation sequencing by establishing the biological and technical validity of a new proprietary method that accommodates very low amounts of RNA from fixed paraffin-embedded tumor tissue, and therefore is practical to use broadly for biomarker discovery and clinical development," said Joffre Baker, Ph.D, chief scientific officer, Genomic Health.  "These findings position Genomic Health to lead in the delivery of next generation cancer diagnostics."

Based on these data, Genomic Health is accelerating its efforts to provide a comprehensive genomic platform for clinical research and development combining both whole transcriptome profiling and mutation analysis next year.  Accordingly, the company is accelerating its investment in information technology infrastructure to support the flow and storage of vast amounts of patient genomic data.

"Next generation sequencing allows researchers to process and analyze large volumes of data in a fraction of the time currently required by conventional gene expression profiling technologies," said Jose Esteban, MD, Providence Saint Joseph Medical Center, Burbank, Calif., a co-investigator of the study.  "New methodology used in this study applies NGS-based whole transcriptome profiling to very low amounts of RNA from FFPE tissue that had been archived for up to 12 years, to provide vast amounts of data, with data quality sufficient for broad biomarker discovery from regions outside the previously identified protein-coding sections of the genome." 

Genomic Health scientists carried out whole transcriptome RNA-Seq on FFPE tumor RNA from a cohort of 136 breast cancer patients with tumor tissue obtained at the time of diagnosis and established clinical outcomes for disease recurrence.  These tumors were originally analyzed by RT-PCR in the biomarker discovery phase of the development of the 21-gene Oncotype DX assay.  Sequencing was carried out using the Illumina® HiSeq 2000 instrument and generated over 40 terrabytes of data for analysis.  The data analysis methods used in this biomarker discovery study were the result of a two year effort to optimize methods for RNA-Seq data normalization and other statistical parameters.  

RNA-Seq results were successfully generated for all patients using RNA inputs of just 100 nanograms.  Bar-coded RNAs were sequenced with two samples per flow cell lane, yielding 43 million reads per each duplexed sample, 69 percent of which uniquely map to the human genome.  Standardized hazard ratios and p-values for the 21 Oncotype DX genes determined by RNA-Seq were comparable to those originally obtained using RT-PCR.  Additionally, whole transcriptome RNA-Seq revealed more than 1,800 new coding and non-coding RNAs associated with breast cancer recurrence risk, many of which belong to previously unrecognized gene networks. Additional research will be performed to determine whether these new genes can be observed in other cohorts and whether they add value beyond the 21 Oncotype DX genes.

The study, "Breast Cancer Recurrence Risk Probed by Whole Transcriptome Next-Generation Sequencing in 136 Patients," is presented on Thursday, December 8 at 7:00 a.m. CT.

About Genomic Health and the Oncotype DX^® Tests
Genomic Health, Inc. (NASDAQ: GHDX) is a molecular diagnostics company focused on the global development and commercialization of genomic-based clinical laboratory services that analyze the underlying biology of cancer allowing physicians and patients to make individualized treatment decisions.

Its lead product, the Oncotype DX Breast Cancer test, has been shown to predict the likelihood of chemotherapy benefit as well as recurrence in early-stage breast cancer to help optimize treatment options.  Oncotype DX is the only test incorporated in published ASCO® and NCCN® breast cancer treatment guidelines for patients with node-negative breast cancer that is estrogen-receptor positive and/or progesterone-receptor positive.(1)  The test is also recognized in international guidelines issued by St. Gallen International Breast Cancer Expert Panel and European Society for Medical Oncology (ESMO).

Physicians also use the Oncotype DX Breast Cancer test to make treatment recommendations for certain node-positive breast cancer patients.  Oncotype DX has been extensively evaluated in thirteen clinical studies involving more than 4,000 breast cancer patients worldwide, including a large validation study published in The New England Journal of Medicine and a chemotherapy benefit study published in The Journal of Clinical Oncology.

The Oncotype DX Colon Cancer test is the first multigene expression test commercially available that has been clinically validated to predict risk of recurrence in patients with stage II colon cancer.  Genomic Health collaborated with the National Surgical Adjuvant Breast and Bowel Project and Cleveland Clinic on a total of four development studies in more than 1,800 to analyze patients with stage II colon cancer.  The final gene panel was then independently evaluated in more than 1,400 stage II colon cancer patients in the QUASAR validation study.

As of September 30, 2011, more than 10,000 physicians in over 60 countries had ordered more than 230,000 Oncotype DX tests.  Genomic Health has a robust pipeline focused on developing tests to optimize the treatment of prostate and renal cell cancers, as well as additional stages of breast and colon cancers.  The company is based in Redwood City, California with European headquarters in Geneva, Switzerland.  For more information, please visit www.genomichealth.com.  To learn more about Oncotype DX tests, visit: www.oncotypedx.com and www.mybreastcancertreatment.org.

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements relating to the company's prospects for its next generation cancer diagnostic platforms and programs; the timing of the availability of its planned next generation platforms; the attributes of its next generation platforms to biomarker discovery and utility as a diagnostic tool; the company's prospects to lead the industry in the development of such applications; the focus of the company's product pipeline, including the ability of the company's tests to impact clinical practice. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially, and reported results should not be considered as an indication of future performance.  These risks and uncertainties include, but are not limited to: our ability to compete against third parties; our ability to develop and commercialize new tests and the timing thereof; unanticipated costs or delays in research and development efforts; the applicability of initial next generation sequencing studies to future results; the risk that we may not obtain or maintain sufficient levels of reimbursement for our existing tests and any future tests we may develop, both domestically and abroad; the risks and uncertainties associated with the regulation of our tests by the FDA and other agencies abroad; the results of clinical and developmental studies; the applicability of clinical study results to actual outcomes; and the other risks set forth in the company's filings with the Securities and Exchange Commission, including the risks set forth in the company's Quarterly Report on Form 10-Q for the period ended September 30, 2011.  These forward- looking statements speak only as of the date hereof.  Genomic Health disclaims any obligation to update these forward-looking statements.

(1) ASCO and NCCN are registered trademarks of the American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN), respectively.  ASCO and NCCN do not endorse any product or therapy.

SOURCE Genomic Health, Inc.