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Oncotype DX, developed by Genomic Health, is a diagnostic test that quantifies the likelihood of disease recurrence in women with early-stage hormone estrogen receptor (ER) positive only breast cancer (prognostic significance) and assesses the likely benefit from certain types of chemotherapy (predictive significance).
Oncotype DX analyzes a panel of 21 genes within a tumor to determine a Recurrence Score. The Recurrence Score is a number between 0 and 100 that corresponds to a specific likelihood of breast cancer recurrence within 10 years of the initial diagnosis, though the score is not validated, though the buckets of Low, Intermediate or High Risk are when the patient receives / abides to 5 years of Tamoxifen. With this information, it may be possible for doctors and patients to make more informed decisions about breast cancer treatment options. Oncotype DX is performed by Genomic Health in its CLIA-certified, CAP-accredited reference laboratory.
Oncotype DX was initially developed for women with early-stage invasive breast cancer with ER+ cancers whose lymph nodes do not contain tumor (node-negative). Typically in these cases, treatment with anti-hormonal therapy, such as tamoxifen or aromatase inhibitors, is planned, and the test can help define whether chemotherapy should or should not be added to that anti-hormone treatment. Oncotype DX remains unproven for use in patients with carcinoma in situ (precancerous) or distant metastatic breast cancer. However, in an analysis of tissue samples from a large clinical trial (SWOG 8814), Oncotype DX demonstrated both prognostic significance (the capability of predicting distant recurrence) and predictive significance ( a second and different characteristic that describes the capability of the test to assess the potential benefit of additional adjuvant chemotherapy) in women with estrogen receptor positive early breast cancer whose lymph nodes show spread of their tumor (node-positive), and the test has also shown similar prognostic and predictive significance in women both either node negative or node positive early breast cancer who received adjuvant treatment with the aromatase inhibitor anastrozole. Moreover, small studies with tumor specimens from breast cancer patients receiving neoadjuvant treatment show similar results and suggest that the test may predict response to neoadjuvant hormonal therapy (oncology) and chemotherapy.
Oncotype DX is a noninvasive test that is performed on a small amount of the tissue removed during the original surgery lumpectomy, mastectomy, or core biopsy, which means no additional invasive procedure is required. After the surgical procedure, the tissue sample is fixed in formalin and embedded in paraffin so it can be preserved for further diagnostic testing.
To perform Oncotype DX, the pathologist will send several thin sections of the formalin-fixed, paraffin-embedded tissue sample to Genomic Health. Oncotype DX uses a highly reproducible laboratory process known as RT-PCR to determine the expression of the 21-gene panel. The Oncotype DX test results are then integrated with other laboratory test results to help doctors formulate a treatment plan based on the unique characteristics of the tumor. Since Oncotype DX became available in 2004, it has been used by over 10,000 physicians to help guide treatment for over 200,000 patients in 60+ countries.
The current list price of Oncotype DX is $4,175.00. Several studies indicate that the use of the Oncotype DX test is cost-effective for the United States, Canada and Japan by providing additional information to help doctors tailor treatment to the individual patient.
From the approximately 25,000 genes in the human genome, Genomic Health identified 250 candidate genes possibly associated with breast cancer tumor behavior. These genes were analyzed in more than 400 patients from three independent clinical studies in order to identify a panel of 21 genes strongly correlated with distant recurrence-free survival.  
The panel consists of 16 cancer genes and five reference genes used to normalize the expression of the cancer genes. The three clinical studies also formed the basis for the Recurrence Score calculation, which combines the gene expression data from the 21-gene panel into a single result and covers 3 of the 7 metastatic pathways.
In collaboration with several independent investigators, Oncotype DX was evaluated in numerous studies involving over 3,300 patients. The results of three key studies appear below.
Oncotype DX was clinically validated in a large, independent multi-center trial of patient samples from the NSABP Study B-14.2 Results demonstrate that Oncotype DX is an accurate and reliable predictor of breast cancer recurrence.
Study conclusion: The Recurrence Score has been validated as quantifying the likelihood of distant recurrence in tamoxifen-treated patients with node-negative, estrogen receptor-positive breast cancer.
Samples of cancer tissue from a clinical trial (NSABP B-20) were used to show that Oncotype DX can predict chemotherapy benefit.
Study conclusion: The Recurrence Score assay not only quantifies the likelihood of breast cancer recurrence in women with node-negative, estrogen receptor-positive breast cancer, but also predicts the magnitude of chemotherapy benefit.
A large clinical study conducted by Kaiser Permanente confirmed in a community setting that Oncotype DX helps predict the likelihood of breast cancer survival at 10 years.
Study conclusion: In a large, population-based study of lymph node-negative patients not treated with chemotherapy, the Recurrence Score was strongly associated with risk of breast cancer death among ER-positive, tamoxifen-treated and -untreated patients.
In ER-positive, mainly post-menopausal tamoxifen-treated lymph node-positive women the Recurrence Score assay quantified the likelihood of breast cancer recurrence and also predicted the magnitude of chemotherapy benefit.
Since the validation of the Oncotype DX Breast Cancer Assay Recurrence Score used a designed study of archived tumor samples from a randomized clinical trial it might be considered Level of Evidence l, a position that Genomic Health has taken. Others, including the NCCN, have considered this as retrospective evidence. Additionally, Oncotype DX is being evaluated in node negative, estrogen-receptor positive breast cancer in a prospective trial, the Trial Assigning IndividuaLized Options for Treatment (Rx) (TAILORx), launched 2006 May, enrolled 10,000 people with intermediate results on the test; results are estimated to be completed in 2014.
Gianni L, Zambetti M, Clark K, et al. Gene expression profiles in paraffin-embedded core biopsy tissue predict response to chemotherapy in women with locally advanced breast cancer. J Clin Oncol. 2005;23(29):7265-77. PMID 16145055
Esteva FJ, Sahin AA, Cristofanilli M, et al. Prognostic role of a multigene reverse transcriptase-PCR assay in patients with node-negative breast cancer not receiving adjuvant systemic therapy. Clin Cancer Res. 2005;11(9):3315-9. PMID 15867229
Cobleigh MA, Tabesh B, Bitterman P, et al. Tumor gene expression and prognosis in breast cancer patients with 10 or more positive lymph nodes. Clin Cancer Res. 2005;11 (24 Pt 1):8623-31. PMID 16361546
Cronin M, Pho M, Dutta D, et al. Measurement of gene expression in archival paraffin-embedded tissues: development and performance of a 92-gene reverse transcriptase-polymerase chain reaction assay. Am J Pathol. 2004;164(1):35-42. PMID 14695316