What is Oncotype DX (Oncotype DXTM)?

What is Oncotype DX

Oncotype DX is a 21-gene expression profiling test that predicts the likelihood of distant breast cancer recurrence and potential benefit from chemotherapy in patients with hormone receptor-positive, HER2-negative early-stage breast cancer. 1, 2

Technical Details and Methodology

• Oncotype DX is a proprietary laboratory-developed test offered by Genomic Health (Redwood City, CA) through a single CLIA-certified laboratory that uses reverse-transcription polymerase chain reaction (RT-PCR) to analyze the expression of 21 genes (16 cancer-related and 5 reference genes) in formalin-fixed, paraffin-embedded breast cancer tissue 1
• The test measures mRNA expression levels of these genes to generate a Recurrence Score (RS) on a scale of 0-100, which correlates to a patient-specific risk of distant recurrence 1, 2
• The analytical performance of the assay has been validated with high precision (CVs of 3.2%-5.7%) and linearity over a >2000-fold range of RNA concentrations 3

Risk Stratification and Interpretation

• Patients are categorized into risk groups based on their Recurrence Score:
  • Low risk (RS <18): 6.8% risk of distant recurrence at 10 years with endocrine therapy alone 1, 4
  • Intermediate risk (RS 18-30): 14.3% risk of distant recurrence at 10 years 1
  • High risk (RS >31): 30.5% risk of distant recurrence at 10 years 1
• The test results help identify patients who may safely avoid chemotherapy (low risk) versus those who would likely benefit from it (high risk) 4, 2

Clinical Validity and Utility

• The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group found adequate evidence for the clinical validity of Oncotype DX in predicting risk of distant metastases in women with hormone receptor-positive, early-stage breast cancer that is either node-negative or node-positive 1
• The test has been shown to predict benefit from chemotherapy through retrospective analyses of prospective trials 4
• Oncotype DX results have been demonstrated to change treatment decisions regarding chemotherapy in clinical practice 1
• However, the EGAPP Working Group found insufficient direct evidence that use of Oncotype DX testing leads to improved clinical outcomes 1, 4

Appropriate Patient Population

• Oncotype DX is most appropriate for patients with:
  • Stage I or II breast cancer 1, 4
  • Hormone receptor (estrogen and/or progesterone)-positive tumors 1, 4
  • HER2-negative status 1, 4
  • Lymph node-negative or limited lymph node-positive (1-3 nodes) disease 1, 5
  • Cases where the benefit of adding chemotherapy to endocrine therapy is uncertain 5, 4

Correlation with Other Factors

• The Recurrence Score has been shown to correlate with:
  • Nottingham histologic grade (higher grade correlates with higher RS) 6
  • Ki-67 expression (higher Ki-67 correlates with higher RS) 7, 6
  • Progesterone receptor status (lower PR expression correlates with higher RS) 7, 6
• Certain histologic subtypes like tubular and lobular carcinomas tend to have lower Recurrence Scores, while micropapillary and high-grade ductal carcinomas often have higher scores 8, 6

Clinical Implementation

• National Comprehensive Cancer Network (NCCN) guidelines recommend considering Oncotype DX testing to refine risk stratification for adjuvant chemotherapy decisions in appropriate patients 4
• The test is most valuable when traditional clinicopathologic features do not clearly indicate whether a patient would benefit from chemotherapy 5, 4
• Economic modeling studies suggest Oncotype DX may be cost-effective in several healthcare systems, though these are based on assumptions about clinical utility that require further confirmation 1, 4

Limitations

• The test does not replace standard clinicopathological assessment but should be used as a complementary tool 5, 4
• Ongoing prospective trials are still needed to provide definitive evidence of clinical utility 1
• Low-grade invasive carcinomas with favorable histology rarely have high-risk Recurrence Scores, potentially limiting the utility of testing in these specific cases 8