What test determines the need for post-operative adjuvant chemotherapy in a patient with Estrogen Receptor (ER) positive, Progesterone Receptor (PR) positive, Human Epidermal growth factor Receptor 2 (HER2) negative, and Node (N) 0 disease?

Genomic Testing for Adjuvant Chemotherapy Decision-Making in ER/PR-Positive, HER2-Negative, Node-Negative Breast Cancer

The 21-gene Recurrence Score (Oncotype DX) is the recommended test to determine the need for adjuvant chemotherapy in patients with ER/PR-positive, HER2-negative, node-negative breast cancer. 1

Recommended Genomic Testing Options

For patients with ER/PR-positive, HER2-negative, node-negative breast cancer, the following genomic tests are supported by clinical guidelines:

1. 21-gene Recurrence Score (Oncotype DX) - First-line recommendation

   • Strongest evidence for clinical utility
   • Only test clinically validated to predict benefit from adjuvant chemotherapy 1
   • Provides a score from 0-100 that stratifies patients into risk categories:
     • Low risk (RS <18): Minimal benefit from chemotherapy
     • Intermediate risk (RS 18-30): Limited benefit from chemotherapy (except in women ≤50 years with RS 16-25)
     • High risk (RS ≥31): Clear benefit from adjuvant chemotherapy

2. Alternative options (if Oncotype DX unavailable):

   • 12-gene risk score (EndoPredict) 1
   • MammaPrint (70-gene assay) - Only for those with high clinical risk per MINDACT categorization 1

Patient Selection for Testing

Genomic testing is most valuable in cases where:

• Decision to administer chemotherapy is uncertain based on traditional clinicopathologic features
• Patient falls into intermediate risk category using traditional prognostic tools
• Need to quantify potential benefit of chemotherapy 2

Testing Limitations and Contraindications

Genomic testing is not recommended in:

• Very small tumors (≤1 cm) where chemotherapy would be unlikely given anyway
• Very large tumors (>5 cm), inflammatory breast cancer, or ≥4 positive nodes where chemotherapy would likely be given regardless 2
• HER2-positive breast cancer 1
• Triple-negative breast cancer 1

Impact on Treatment Decisions

Implementation of genomic testing has significantly reduced unnecessary chemotherapy use:

• Studies show 34.7% of patients can be spared chemotherapy based on Oncotype DX results 3
• At comprehensive cancer centers, chemotherapy use decreased from 23.8% to 10.9% after implementation of Oncotype DX testing 4

Clinical Interpretation Algorithm

1. Obtain Oncotype DX test for ER/PR-positive, HER2-negative, node-negative breast cancer patients
2. Interpret Recurrence Score:
   • RS <18: Endocrine therapy alone (chemotherapy not indicated)
   • RS 18-30:
     • If patient >50 years: Endocrine therapy alone
     • If patient ≤50 years with RS 16-25: Consider adding chemotherapy
   • RS ≥31: Endocrine therapy plus chemotherapy

Common Pitfalls to Avoid

• Don't rely solely on traditional clinicopathologic features - Studies show these features alone lead to overtreatment with chemotherapy 3
• Don't use genomic testing for all patients - Testing is not valuable in cases where treatment decision is already clear based on tumor characteristics
• Don't use alternative genomic tests as equivalent to Oncotype DX - Other assays should not be considered equivalent with respect to data generated or risk stratification 1
• Don't ignore age in intermediate risk scores - Younger patients (≤50 years) with RS 16-25 may benefit from chemotherapy while older patients may not 1

By following these evidence-based recommendations, clinicians can make more informed decisions about adjuvant chemotherapy, potentially sparing many patients from unnecessary treatment while ensuring those who would benefit receive appropriate therapy.