Oncotype DX, is a commercial diagnostic test that estimates the likelihood of disease recurrence in women with early-stage hormone estrogen receptor (ER) positive only breast cancer (prognostic significance). There is emerging evidence that such tests may also provide information about the likely benefit from 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.
The test 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.
Cost and cost-effectiveness
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 in lymph node negative patients for the United States, Canada and Japan by providing additional information to help doctors tailor treatment to the individual patient. The cost-effectiveness of Oncotype DX in lymph node positive patients remains highly uncertain.
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.
Key clinical studies
The results of prospectively conducted research providing evidence for the clinical utility of Oncotype DX are not yet available. In the setting of collaboration between several independent investigators and the manufacturer, the clinical validity of Oncotype DX was evaluated retrospectively in selected studies involving over 3,300 patients. The results of key studies appear below.
NSABP Study B-14
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.
NSABP Study B-20
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.
The clinical validity and prognostic ability of Oncotype DX was compared with two competing tests, the PAM50 risk of recurrence (ROR) score by NanoString Technologies and IHC4 which is an index of distant recurrence risk derived from immunohistochemical assessment of ER, progesterone receptor, human epidermal growth factor receptor 2 (HER2), and Ki67.
Study conclusion: PAM50 ROR provides more prognostic information in endocrine-treated patients with ER-positive, node-negative disease than Oncotype DX RS. 
Kaiser Permanente study
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.
SWOG 8814 study
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.
Oncotype DX TAILORx Trial
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.
- Breast cancer classification
- Personalized medicine
- Personal genomics
- Cancer genomics (Oncogenomics)
- Oncotype DX Colon Cancer Assay
- Hornberger J, Cosler LE, Lyman GH. Economic analysis of targeting chemotherapy using a 21-gene RT-PCR assay in lymph-node-negative, estrogen-receptor-positive, early-stage breast cancer. Am J Manag Care. 2005;11(5):313-24. PMID 15898220
- Tsoi DT, Inoue M, Kelly CM, Verma S, Pritchard KI. Cost-Effectiveness Analysis of Recurrence Score-Guided Treatment Using a 21-Gene Assay in Early Breast Cancer. Oncologist. 2010 Apr 26. PMID 20421264
- Kondo M, Hoshi SL, Ishiguro H, Yoshibayashi H, Toi M. Economic evaluation of 21-gene reverse transcriptase-polymerase chain reaction assay in lymph-node-negative, estrogen-receptor-positive, early-stage breast cancer in Japan. Breast Cancer Res Treat. 2008 Nov;112(1):175-87. PMID 18075786
- Lyman GH, Cosler LE, Kuderer NM, Hornberger J. Impact of a 21-gene RT-PCR assay on treatment decisions in early-stage breast cancer: an economic analysis based on prognostic and predictive validation studies. Cancer. 2007 Mar 15;109(6):1011-8. PMID 17311307
- Hall PS, McCabe C, Stein RC, Cameron D. J Economic evaluation of genomic test-directed chemotherapy for early-stage lymph node-positive breast cancer. J Natl Cancer Inst. 2012 Jan 4;104(1):56-66. PMID 22138097
- 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. PMID 15591335
- 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 the 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 the Thirty-ninth Meeting of the American Society of Clinical Oncology. May 31-June 3, 2003; Chicago, IL. Abstract #3415.
- Paik S, Shak S, Tang G, 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. PMID 16720680
- J Clin Oncol. 2013;31(22):2783-90. PMID 23816962
- Habel LA, Shak S, Jacobs MK, et al. A population-based study of tumor gene expression and risk of breast cancer death among lymph node-negative patients. Breast Cancer Res. 2006;8(3):R25. PMID 16737553
- Albain KS, Barlow WE, Shak S et al. (January 2010). "Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial". Lancet Oncol. 11 (1): 55–65. doi:10.1016/S1470-2045(09)70314-6. PMC 3058239. PMID 20005174.
- Andre F, Delaloge S (January 2010). "First-generation genomic tests for breast cancer treatment". Lancet Oncol. 11 (1): 6–7. doi:10.1016/S1470-2045(09)70347-X. PMID 20005177.
- National Cancer Institute. The TAILORx Breast Cancer Trial.http://www.cancer.gov/clinicaltrials/noteworthy-trials/tailorx accessioned 2010 October 29
- Zacks Investment Research. Positive Data For Genomics Oncotype. posted on 2010 Dec 15 and accessioned 2010 Dec 19 at http://www.dailymarkets.com/stock/2010/12/15/positive-data-for-genomics-oncotype-2/
- U.S. National Institutes of Health. (ClinicalTrials.gov) Hormone Therapy With or Without Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Negative Breast Cancer (The TAILORx Trial).
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