Oncotype DX

Oncotype DX™, created by Genomic Health, is a diagnostic test that quantifies the likelihood of disease recurrence in women with early-stage breast cancer and assesses the likely benefit from certain types of chemotherapy. With this information, it may be possible for doctors and patients to make more informed decisions about breast cancer treatment options. 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. 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.

Cost and cost-effectiveness
The current list price of Oncotype DX is $3,650. Given that chemotherapy can cost tens of thousands of dollars per year, per patient, the test can actually be cost-effective, by providing additional information to help doctors tailor treatment to the individual patient.1

Development
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.2-4

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.

Key clinical studies
In collaboration with several independent investigators, Oncotype DX was evaluated in numerous studies involving over 2,600 patients. The results of three 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
A study of patient samples from the NSABP Study B-20 made the finding that Oncotype DX can predict chemotherapy benefit.5

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.

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.6

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.

Additional Publications
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