What is the role of Oncotype DX (Oncotype DXTM) in guiding treatment decisions for patients with early-stage, hormone receptor-positive, HER2-negative breast cancer?

Role of Oncotype DX in Guiding Treatment Decisions for Early-Stage Breast Cancer

Oncotype DX testing is recommended for patients with hormone receptor-positive, HER2-negative, early-stage breast cancer to guide adjuvant chemotherapy decisions, though direct evidence of improved clinical outcomes is still pending from ongoing trials. 1, 2

Clinical Validity and Utility

• Oncotype DX has established clinical validity in predicting risk of distant metastases in women with hormone receptor-positive early-stage breast cancer, in both node-negative and node-positive disease 1
• The test provides a Recurrence Score (RS) on a scale of 0-100, stratifying patients into risk categories that correlate with risk of distant recurrence 3
• While there is evidence that Oncotype DX predicts benefit from chemotherapy and changes treatment decisions, the EGAPP Working Group found insufficient direct evidence that its use leads to improved clinical outcomes 1
• Multiple studies demonstrate that Oncotype DX testing changes treatment recommendations in 12-74% of patients, with an overall trend toward decreased chemotherapy use (13-34% fewer patients recommended for chemotherapy) 1

Patient Selection for Testing

• Most appropriate for patients with stage I or II breast cancer, hormone receptor-positive tumors, HER2-negative status, and lymph node-negative or limited lymph node-positive disease 2, 3
• The National Comprehensive Cancer Network (NCCN) recommends Oncotype DX to refine risk stratification for adjuvant chemotherapy in node-negative, ER-positive, HER2-negative breast cancers larger than 0.5 cm 2
• Testing is particularly valuable in cases where the benefit of adding chemotherapy to endocrine therapy is uncertain based on traditional clinicopathological features 2, 4
• Less useful in patients with very small tumors (≤0.5 cm) or those with high-risk features where chemotherapy would likely be recommended regardless of test results 1

Interpretation of Recurrence Scores

• Low RS (<18): 6.8% risk of distant recurrence at 10 years with endocrine therapy alone 3
• Intermediate RS (18-30): 14.3% risk of distant recurrence at 10 years 3
• High RS (>31): 30.5% risk of distant recurrence at 10 years with clear benefit from adjuvant chemotherapy 2, 3
• Recent data suggests that patients ≤45 years with RS ≥18 may benefit from the addition of chemotherapy to endocrine therapy 5

Clinical Impact on Treatment Decisions

• Studies show that Oncotype DX testing leads to changes in treatment decisions in a significant proportion of patients 1
• A survey of 7,375 women treated at cancer centers in the United States found an overall decrease in chemotherapy use from 53.9% to 47.0% after Oncotype DX testing (p < 0.001) 1
• Treatment changes were particularly significant among patients ≤50 years, those with luminal B tumors, stage II and IIIA disease, and node-positive disease 6
• Physician factors also influence treatment decisions following Oncotype DX testing, with male oncologists less likely to recommend chemotherapy and more experienced oncologists (>20 years) more likely to recommend chemotherapy 7

Ongoing Clinical Trials

• The TAILORx trial (estimated completion 2017) is designed to determine the benefit of chemotherapy for women with intermediate-risk Oncotype DX results 1
• The RxPONDER trial (estimated completion 2022) will compare disease-free survival for women with node-positive invasive breast cancer (1-3 nodes) and RS ≤25 treated with either endocrine therapy alone or endocrine therapy plus chemotherapy 1
• These prospective trials are expected to provide more definitive evidence regarding clinical utility in the target population 1

Limitations and Considerations

• Approximately 37% of patients fall into the intermediate-risk category, where chemotherapy benefit remains uncertain 1
• The benefits of avoiding chemotherapy toxicity may outweigh the potential harm from recurrence in some patients, but both physicians and patients should be aware of potential risks when foregoing chemotherapy based on RS results 1
• Some studies suggest that standard morphoimmunohistologic variables can be used to estimate the recurrence score, potentially reducing the need for Oncotype DX testing in cases where the estimated score is clearly high or low 8
• Despite widespread adoption, there are indications that eligible African-American women may be tested at lower rates than white women 1

Cost-Effectiveness

• Economic modeling studies suggest Oncotype DX may be cost-effective or cost-saving in several healthcare systems, though these are based on assumptions about clinical utility that require confirmation 1
• The UK National Institute for Health and Care Excellence (NICE) recommends Oncotype DX as an option for guiding adjuvant chemotherapy decisions for people with ER+, LN−, HER2− early breast cancer assessed as being at intermediate risk 1, 2