• Login
• Press Room
• Register for Updates
• Contact Us

HEALTHCARE PROFESSIONALS

• Clinical Summary
• ASCO/NCCN Guidelines
• Case Studies
• Ordering Oncotype DX
• Insurance Information
• Submitting a Sample
• Obtaining Reports
• Reading Reports
• Ongoing Research (TAILORx)
• Publications
• FAQs

What is the Oncotype DX^® assay?

• Overview
• Which Patients?
• Recurrence Score^® Result
• Validated Clinical Benefits
• Insight Beyond Traditional Markers
• Impact on Treatment Decisions
• Quantitative Single-Gene Scores
• Expansion of Clinical Utility
• Underlying Technology
• References
• Downloadable Files

Overview

Since not all women benefit from chemotherapy equally, the Oncotype DX assay is a 21-gene assay that provides an individualized prediction of chemotherapy benefit and 10-year distant recurrence to inform adjuvant treatment decisions in certain women with early-stage breast cancer.

The Oncotype DX Assay:

• Supports your treatment decisions—The only proven, multi-gene expression assay recommended in the ASCO and NCCN guidelines
• Informs treatment decisions and improves confidence for physicians and patients—Studies suggest that the results of the assay help change breast cancer treatment decisions in approximately 30% of cases¹
• Offers expanded clinical utility—Enhanced reports now include quantitative ER, PR and HER2 values
• Provides extensive coverage—Insurance coverage for Medicare patients, and 90% of privately insured lives in the U.S.

Extensively Validated, Ordered and Reimbursed

• As the only multi-gene expression assay recommended in the ASCO and NCCN guidelines, the Oncotype DX assay is a proven standard to inform your treatment decisions
• Over 65,000 patients have received the information provided by the Oncotype DX assay
• The clinical value of the Oncotype DX assay was shown in clinical studies involving nearly 4,000 patients
• Over 7,500 physicians have ordered the Oncotype DX assay
• Insurance coverage for Medicare patients, and 90% of privately insured lives in the U.S.
• Genomic Health is a CLIA-certified, CAP-accredited reference laboratory and is a leader in the field of cancer genomics

Which Patients?

The Oncotype DX assay provides clinical experience information:

• For women with node-negative, estrogen-receptor-positive invasive breast cancer

AND

• For post-menopausal women with node-positive, hormone-receptor-positive invasive breast cancer

Recurrence Score^® Result

Because breast cancer is a heterogeneous disease, it is important to have an assay that provides a continuous view of the biology.

• The likelihood of distant recurrence at 10 years increases continuously with an increase in the Oncotype DX assay Recurrence Score^® result
• The quantitative nature of PCR allows for a continuous score as opposed to a binary result (low vs. high only). This method is designed to provide you and your patients with an individual score and to help inform your treatment plan

Validated Clinical Benefits

Numerous studies have shown that the Oncotype DX assay delivers consistent, reproducible and accurate results. Based on the nearly 4,000 patients studied to date, the Oncotype DX assay delivers clinically valuable information that can be used to help make decisions about adjuvant therapy. The assay informs your treatment options and can give patients more confidence in their decisions.

NSABP B-14—Prospective Analysis of Archival Tissue: Likelihood of Distant Breast Cancer Recurrence⁴

• 668 stage I or II, node-negative, estrogen-receptor-positive, tamoxifen-treated patients
• Validation conducted using prospectively defined endpoints
• The Oncotype DX assay validated as quantifying the likelihood of distant breast cancer recurrence for individual patients
• Recurrence Score result performance is superior to that of patient age and tumor size in prognostic power and superior to tumor grade in reproducibility

In a statistical analysis in which distant recurrence was evaluated in relation to the Recurrence Score (RS) result, age and tumor size, the RS result provided predictive power that was independent of those traditional prognostic variables. When it was combined with age and tumor size data, only the Recurrence Score result remained statistically significant.

NSABP B-20—Prospective Analysis of Archival Tissue: Magnitude of Benefit from Chemotherapy⁵

• The Oncotype DX assay predicts the magnitude of benefit from chemotherapy: Proportion without distance recurrence at 10 years with vs. without treatment
• 651 patient samples that were node-negative, estrogen-receptor-positive from the NSABP B-20 Study were studied
  • -227 patients were treated with tamoxifen alone
  • -424 patients were treated with chemotherapy (CMF) and tamoxifen
• Patients with tumors that have Recurrence Score results of:
  • -Greater than or equal to 31 have a substantial absolute benefit from chemotherapy
  • -18 to 30 did not appear to receive a substantial benefit from chemotherapy, but a clinically important benefit cannot be excluded
  • -Less than 18 derive minimal, if any, benefit from chemotherapy

Insight Beyond Traditional Markers

The Recurrence Score result provides additional insight into the likelihood of breast cancer recurrence that goes beyond traditional measures such as patient age, tumor size, ER status and tumor grade.

Impact on Treatment Decisions

The question of whether the Oncotype DX assay report impacts treatment decisions has been explored in more than eight studies. One of these studies, a multi-center study with 17 medical oncologists, was designed to prospectively examine how the Recurrence Score result impacts adjuvant treatment decision making in breast cancer.

• In 31.5% of cases, medical oncologists changed their recommendation after receiving the Recurrence Score result, and the great majority of these changes were from "chemo-hormonal therapy" to "hormonal therapy" alone
• In 76% of cases, the physician agreed or strongly agreed with the statement, "I am more confident in my treatment recommendation after ordering the Oncotype DX assay"
• Patients reported significantly lower conflict about the decision for adjuvant treatment, greater satisfaction with decision making and decreased situational anxiety

Multiple studies in both the academic and community settings were pooled to examine the treatment selection based on Recurrence Score results. A low Recurrence Score result provided actionable information for physicians that led to a recommendation for no chemotherapy (91%) and resulted in no chemotherapy given (95%) in virtually all low Recurrence Score result patients.

Quantitative Single-Gene Scores

The Oncotype DX assay report now includes quantitative scores for estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) gene expression by RT-PCR (all reports generated as of September 20, 2008). ER, PR and HER2 are three of the genes measured in the determination of the Recurrence Score result.

ER and PR

• Continuous Measurement by RT-PCR:
  ER/PR status is critical in determining the use and estimating the benefit of adjuvant hormonal therapy. Breast cancers show a broad range of hormone receptor expression, and RT-PCR is able to accurately convey this continuum. RT-PCR is able to measure ER and PR as a continuous distribution of gene expression over a 3,000-fold and 1,000-fold range, for ER and PR, respectively.A quantitative ER Score can provide further insight into treatment decisions by helping to determine the magnitude of tamoxifen benefit for an individual patient (the higher the ER score, the greater the likelihood of tamoxifen benefit).
• Concordance:
  The Oncotype DX assay determines ER and PR status (positive or negative) by measuring gene expression at the RNA level. There is a high concordance between ER and PR status as determined by the Oncotype DX assay and by immunohistochemistry (IHC), which measures ER and PR gene expression at the protein level.Studies were performed with ECOG (E2197 study, 769 patient samples) and Northern California Kaiser Permanente (607 patient samples):
• The Relationship Between ER/PR and the Recurrence Score Result:
  The Recurrence Score (RS) result can be either low or high for high ER levels. The RS result combines the ER level (related to response to tamoxifen) with the expression of other genes. The RS result is a better predictor of distant recurrence at 10 years given 5 years of tamoxifen therapy in the ER+ population than  ER/PR status is alone.

HER2

HER2 is an important marker for therapeutic decision-making for patients with breast cancer, and its measurement significantly impacts the chosen course of treatment.

• Quantitative HER2 Information:
  A HER2 Score by the Oncotype DX assay is another measure for clinicians and patients to determine HER2 status, and it provides further insight into individual patients’ breast cancer tumor biology, although the Recurrence Score result remains the best tool for assessing prognosis and prediction of chemotherapy benefit.
• Highly Concordant with IHC¹² and FISH¹³:
  The Oncotype DX assay’s concordance with IHC and FISH meets or exceeds the ASCO/CAP guidelines requirement of 95% for determination of HER2 status.
• Added Clinical Information:
  Many clinicians who rely on the Oncotype DX assay for treatment planning have requested that Genomic Health also report a quantitative HER2 Score as this is already a component of the Recurrence Score result. – To provide further clarification especially in cases of equivocal IHC and/or FISH results or discordance between FISH and IHC.
• Addressing a Limitation with Current Testing:
  The impact of preanalytical variability can be minimized by “normalization” strategies used in quantitative gene expression assessment as performed by quantitative RT-PCR by the Oncotype DX assay.

Expansion of Clinical Utility

Genomic Health is committed to expanding the clinical utility of the Oncotype DX assay—expanding the clinical experience information to additional populations of patients with breast cancer and bringing more valuable information to physicians.

• A recent study demonstrates that the Oncotype DX assay Recurrence Score result is informative for post-menopausal patients with node-positive, hormone-receptor-positive (HR+) breast cancer¹¹
• The Oncotype DX assay is a predictive assay for chemotherapy (CAF) benefit (change in disease-free survival)
• The Oncotype DX assay is a prognostic for disease-free survival at 5 years

Underlying Technology

Video: Underlying Technology

The Oncotype DX Assay Process

As a multi-gene diagnostic assay, the Oncotype DX assay is designed to support individualized treatment planning. The assay provides a quantitative assessment of the likelihood of chemotherapy benefit and distant recurrence, which may increase confidence that the treatment plan is tailored to the individual patient.

The Oncotype DX assay is performed in the licensed Genomic Health laboratory where the assay was developed. First, RNA is extracted from the breast cancer tumor specimen and purified. Next, the RNA is analyzed using a technique called real-time RT-PCR (reverse transcriptase-polymerase chain reaction). Finally, the Recurrence Score result is calculated from the gene expression results.

Advantages of RT-PCR

The Oncotype DX assay analyzes the expression of a panel of 21 genes from a tumor specimen using a technique called RT-PCR. A high-throughput, real-time RT-PCR method was developed to analyze the expression of select genes simultaneously. It is sensitive, specific, highly reproducible and has a wide dynamic range. RT-PCR is a mature technology that is routinely utilized in several clinical applications including viral load testing for HIV.

To quantify gene expression, RNA is extracted from formalin-fixed, paraffin-embedded (FPET) tumor tissue and subjected to DNase I treatment. Total RNA content is measured and the absence of DNA contamination is verified. Reverse transcription is performed and is followed by quantitative TaqMan^® (Roche Molecular Systems, Inc.) RT-PCR reactions in 384-well plates. The expression of each of 16 genes is measured in triplicate and then normalized relative to a set of five reference genes.

The Oncotype DX assay standardized testing methods have been optimized to minimize variability due to:

• Tissue preparation method: FPET vs. fresh frozen
• Tumor block age, storage and variability in preparation
• Heterogeneity within and between FPET blocks
• Heterogeneity with respect to enriched tumor and non-tumor areas within an FPET block

Oncotype DX Assay Development

The Oncotype DX assay was developed in four steps. Each of these steps is described in detail below.

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 result 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 U.S., 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 techniques, the expression of most genes—relative to a set of reference genes—can be measured. To develop the Oncotype DX assay, Genomic Health researchers optimized RT-PCR technology 1) for high-throughput, real-time quantitation of specific RNA in FPET, and 2) to be reproducible regardless of the variability inherent in tumor blocks.

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.

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 result calculation, which combines the gene expression data from this gene panel into a single result.

Step 4. Prospective clinical validation of the 21-gene panel and Recurrence Score result calculation

The Oncotype DX assay gene panel and Recurrence Score result 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).

21-Gene Panel Used to Calculate Recurrence Score Result

The Oncotype DX assay gene panel was selected from the published literature, a genomics database and experiments based on DNA arrays performed on fresh-frozen tissue. The Recurrence Score result algorithm was derived from 3 studies of breast cancer patients and then was clinically validated in multiple independent studies.

• The Recurrence Score result is calculated from the expression of 16 cancer-related genes and 5 reference genes used to normalize the expression of those cancer genes
• In clinical studies, the 16 cancer genes demonstrated a consistent statistical link to distant breast cancer recurrence, as well as robust predictive power regarding chemotherapy benefit

21-Gene Panel Used to Calculate Recurrence Score Result:
16 cancer genes and
5 reference genes from
3 studies

References

For a larger listing of Oncotype DX assay-related studies, visit our Publications page.

1. Lo SS, Norton J, Mumby PB, et al. Prospective multicenter study of the impact of the 21-gene Recurrence Score (RS) assay on medical oncologist (MO) and patient (PT) adjuvant breast cancer (BC) treatment selection. Presented at the 43rd Annual Meeting of the American Society of Clinical Oncology (ASCO). June 1-5, 2007; Chicago, IL. Abstract #577.
2. Harris L, Fritsche H, Mennel R, et al. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol. 2007;25(33):5287-312.
3. NCCN Clinical Practice Guidelines in Oncology™ Breast Cancer, (Version 2.2008) http://www.nccn.org (Accessed 1/9/08).
4. Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351(27):2817-26.
5. Paik S, Tang G, Shak S, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen-receptor-positive breast cancer. J Clin Oncol. 2006;24(23):3726-34.
6. Hall P, Skrzypczak S, Palmer G. Low Recurrence Score by the Oncotype DX breast cancer assay rarely results in recommendation for or administration of chemotherapy: a pooled analysis.
7. Goldstein L, Ravdin P, Gray R, et al. Prognostic utility of the 21-gene assay compared with Adjuvant! in hormone-receptor-positive(HR) operable breast cancer with 0-3 positive axillary nodes treated with adjuvant chemohormonal therapy (CHT): an analysis of intergroup trial E2197. Presented at the 30th Annual San Antonio Breast Cancer Symposium. December 13-16, 2007; San Antonio, TX. Abstract #63.
8. Badve SS, Baehner FL, Gray R, et al. Estrogen and progesterone-receptor status in ECOG 2197: comparison of immunohistochemistry by local and central laboratories and quantitative reverse transcription polymerase chain reaction by central laboratory. J Clin Oncol. 2008;26(15):2473-2481.
9. Baehner FL, Maddala T, Alexander C, et al. A Kaiser Permanente population-based study of ER and PR expression by the standard method, immunohistochemistry (IHC), compared to a new method, quantitative reverse transcription polymerase chain reaction (RT-PCR). Presented at the ASCO Breast Cancer Symposium. September 7-8, 2007; San Francisco, CA. Abstract #88.
10. Data on file.
11. Albain K, Barlow W, Shak S, et al. Prognostic and predictive value of the 21-gene Recurrence Score assay in postmenopausal, node-positive, ER-positive breast cancer. Presented at the 30th Annual San Antonio Breast Cancer Symposium. December 13-16, 2007; San Antonio, TX. Abstract #10.
12. Baehner FL et al. HER2 concordance between central laboratory immunohistochemistry & quantitative reverse transcription polymerase chain reaction in intergroup trial E2197. Presented at the ASCO Breast Cancer Symposium. September 6, 2008; Washington, D.C. Abstract #13.
13. Baehner FL et al. HER2 assessment in a large Kaiser Permanente case-control study: comparison of FISH and quantitative RT-PCR performed by central laboratories. Presented at the ASCO Breast Cancer Symposium. September 6, 2008; Washington, D.C. Abstract #41.

Downloadable Files

Presentation of the Development and Clinical Validation of Oncotype DX
Presentation of Genomics in Breast Cancer Overview for Nurses
Download Clinical Summary here