Below are answers to frequently asked questions about the Oncotype DX® assay.
The Oncotype DX diagnostic assay predicts the likelihood of chemotherapy benefit for those patients and quantifies the likelihood of breast cancer recurrence in women with newly diagnosed, stage I or II, node-negative, estrogen receptor-positive breast cancer treated with tamoxifen. A recent study also indicated that the Oncotype DX assay may also be prognostic and predictive of added chemotherapy (CAF) benefit for postmenopausal women with node-positive, hormone-receptor-positive breast cancer treated with tamoxifen. The test analyzes the expression of a panel of 21 genes.
Research and validation studies have already been performed on the 21-Gene Oncotype DX Breast Cancer Assay for the following indications: N-, ER+; Single Gene Reporting of ER/PR; N+. The Oncotype DX assay for these indications is currently commercially available. The Oncotype DX assay was developed and its performance characteristics were determined by Genomic Health, Inc. The laboratory is regulated under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) as qualified to perform high-complexity clinical testing. The Oncotype DX assay is used for clinical purposes, and it should not be regarded as investigational or for research. Oncotype DX assay results are adjunctive to the ordering physician’s workup.
The Oncotype DX assay is clinically validated for newly diagnosed breast cancer patients who are either:
- Stage I or II node-negative, estrogen-receptor-positive
- Postmenopausal, node-positive, hormone-receptor-positive
The Oncotype DX assay can be ordered as soon as resected tumor tissue is available for submission to Genomic Health. The Oncotype DX assay is intended for use in women newly diagnosed with early stage invasive breast cancer who are either stage I/II node-negative, estrogen-receptor-positive or postmenopausal, node-positive, hormone-receptor-positive and provides information that may be used to enhance treatment planning.
The Oncotype DX assay was developed in extensive laboratory and clinical studies and was validated in an independent clinical study with prospectively-defined endpoints. The results of the initial validation study of the Oncotype DX assay in stage I/II, node-negative, estrogen-receptor-positive breast cancer were published in The New England Journal of Medicine (December 30, 2004).
Both ASCO (American Society of Clinical Oncology) and NCCN (National Comprehensive Cancer Network) have included the Oncotype DX assay in their guidelines as an option to help determine whether patients with node-negative, estrogen-receptor-positive breast cancer will benefit from chemotherapy.
The Oncotype DX Assay Recurrence Score result is provided on a scale of 0 to 100. Each Recurrence Score result is calculated based on the results of the patient's tumor gene expression profile. For node-negative, estrogen-receptor-positive breast cancer patients treated with tamoxifen, the Recurrence Score result correlates to a specific likelihood of distant recurrence as observed in the clinical validation study as well as likelihood of chemotherapy benefit (CMF/MF). For node-positive, estrogen-receptor-positive post-menopausal patients treated with tamoxifen, the report form now includes the SWOG 8814 study which evaluated risk of recurrence or death vs the Recurrence Score result (both prognosis and likelihood of chemotherapy benefit [CAF]).
The identification of the gene panel for the Oncotype DX assay started with an extensive analysis of the human genome. Following the identification of a large set of genes associated with breast cancer, three studies explored the expression of 250 genes in patient tumor samples that were obtained at the time of initial diagnosis. The results of these studies were analyzed and used to develop a 21-gene assay that incorporated the genes which consistently correlated with distant recurrence-free survival. This assay was then validated, using prospectively-defined endpoints, in an independent clinical study of over 650 patient tumor samples from the tamoxifen-alone arm of the landmark NSABP Study B-14.
In addition to quantifying breast cancer recurrence risk, the Oncotype DX assay also assesses the benefit from chemotherapy.1
Materials necessary for sample collection and submission are provided in the Oncotype® Specimen Kit, which can be ordered through Genomic Health. Tumor samples are submitted to the Genomic Health Laboratory for analysis. Click here for more information about ordering the assay.
The Oncotype DX assay is performed using formalin-fixed, paraffin-embedded invasive breast tumor tissue obtained by lumpectomy, mastectomy or core biopsy.
The Oncotype DX assay requires either one tumor block OR six 10-micron sections of tissue (three in each of two tubes) and an H&E slide from the same block. When blocks are submitted, typically 35 to 65 microns of tissue will be used.
The results of the Oncotype DX assay are presented as a Recurrence Score result (0-100). In addition to the individual test results, an overview of the clinical validation study is provided which correlates Recurrence Score result with likelihood of distant recurrence at 10 years for node-negative, ER-positive patients treated with tamoxifen. The node-negative report now includes results from the NSABP B-20 study of chemotherapy benefit according to the Recurrence Score result for node-negative, estrogen-receptor-positive patients treated with tamoxifen. The node-positive report includes results from the SWOG 8814 study of prognosis and chemotherapy benefit for node-positive, hormone-receptor-positive post-menopausal patients treated with tamoxifen. The final page of both reports displays the ER (Estrogen Receptor), PR (Progesterone Receptor) and HER2 Scores, based on the assessment of the expression of each of these genes. The report form itself is delivered via fax, overnight mail or secure online transfer. Click here for more information on reports.
The results of the Oncotype DX assay will typically be available within 10 to 14 days from the date the specimen is received at Genomic Health. The results of the test will be returned via fax, overnight mail or secure online transfer.
The Oncotype DX assay is available and the Genomic Health laboratory is accepting patient samples. As of December 2007, the assay has been ordered by over 7,500 MDs for over 65,000 patients since January 2004. Click here for information about sample submission.
Genomic Health is pleased that many payers representing more than 200 million lives covered have established favorable coverage policies for the Oncotype DX assay for node-negative, estrogen-receptor-positive patients. It is unknown at this time whether payers will cover the Oncotype DX assay for patients with node-positive breast cancer. Through our Genomic Access Program (GAP), authorized healthcare providers can request that a benefits investigation be performed for a patient to provide her with information about her specific coverage and potential financial responsibility. Click here for more information about insurance coverage and reimbursement.
Genomic Health is able to accept specimens from outside the U.S. for the Oncotype DX Breast Cancer Assay. In addition to all other requirements for these specimens, payment is required prior to processing. Payment can be accepted in the form of valid credit card information, submitted on the Requisition Form or an international money order in U.S. dollars. A Customs Declaration is also required for the specimen to be accepted into the United States. A sample Customs Declaration can be found here. Oncotype Specimen Kits comply with international packaging regulations for diagnostic specimens (IATA 650 Packaging Instruction). Please contact our Customer Service Department, 866-ONCOTYPE (866-662-6897), in advance to discuss any special requirements.
Genomic Health's research has revealed that both ER and PR, as measured using RT-PCR by the Oncotype DX assay, have a wide range of expression across a continuum that is not reported by other methods that are commonly available. Based on this information, and given that the ER and PR scores are generated with the analysis that generates the Recurrence Score result, Genomic Health concluded that reporting the quantitative ER and PR Scores together with the Recurrence Score result as part of the Oncotype DX assay report was appropriate to provide additional insight into the biology of individual tumors. These data are included in reports generated on or after February 1, 2008.
ER and PR by IHC measure protein expression by staining receptors on the cell surface. Quantitative ER and PR by RT-PCR measure the RNA expression of these genes. Several studies have demonstrated high concordance between ER and PR by IHC and quantitative ER and PR by RT-PCR. -+ ER and PR Scores constitute a precise, reproducible and alternate method to determine a patient's ER and PR status.
The quantitative ER and PR Scores can:
- Help determine the likelihood that an individual patient will derive a substantial benefit from tamoxifen
- Provide additional information for clinical decision making for a patient whose ER protein expression is borderline positive by IHC or reported as uncertain
- Provide further insight into the Recurrence Score result
Many clinicians who rely on Recurrence Score results for treatment planning have requested that Genomic Health also report a quantitative HER2 Score as a means to complement current testing and potentially provide further clarification of conflicting or ambiguous results. The Recurrence Score result remains the best tool for assessing prognosis and prediction of chemotherapy benefit.
The quantitative HER2 score can provide a greater level of confidence in cases of equivocal IHC and/or FISH results or discordance between FISH and IHC.
- The data on chemotherapy benefit is derived from the NSABP Study B-20 which compared hormonal therapy alone versus CMF-based chemotherapy and hormonal therapy.