What is the recommended treatment approach for a postmenopausal woman with Hormone Receptor (HR)-positive, node-negative breast cancer and an Oncotype DX (Genomic Test) recurrence score of 16-25?

Treatment for Oncotype DX Score 16-25 in Postmenopausal Women with HR-Positive, Node-Negative Breast Cancer

For postmenopausal women with HR-positive, HER2-negative, node-negative breast cancer and an Oncotype DX recurrence score of 16-25, endocrine therapy alone is recommended without the addition of chemotherapy, as the TAILORx trial demonstrated similar 9-year disease-free survival rates between endocrine therapy alone and chemoendocrine therapy in this population. 1

Age-Based Treatment Algorithm

Postmenopausal Women (or >50 years old)

• Endocrine therapy alone is the standard of care for recurrence scores 16-25, as no chemotherapy benefit was demonstrated in the TAILORx trial for this age group 1
• The 9-year invasive disease-free survival was 83.3% with endocrine therapy alone versus 84.3% with chemoendocrine therapy (hazard ratio 1.08; 95% CI 0.94-1.24) 2
• Distant recurrence rates at 9 years were 94.5% with endocrine therapy alone versus 95.0% with chemoendocrine therapy 2

Premenopausal Women (or ≤50 years old)

• Chemotherapy followed by endocrine therapy should be offered for recurrence scores 16-25, as subset analysis from TAILORx showed significantly lower rates of distant recurrence with chemotherapy addition in this age group 1
• The chemotherapy benefit varied with the combination of recurrence score and age (P=0.004 for interaction) 2
• The NCCN 2024 guidelines specifically recommend adjuvant chemotherapy followed by endocrine therapy ± ovarian suppression/ablation for premenopausal patients with RS 16-25 1

Endocrine Therapy Selection for Postmenopausal Women

First-Line Options

• Aromatase inhibitor (anastrozole, letrozole, or exemestane) for 5 years is the preferred initial approach (category 1) 1
• Alternatively, tamoxifen for 5 years followed by an aromatase inhibitor for up to 5 years (total 10 years) is acceptable 1
• Sequential therapy with tamoxifen for 2-3 years followed by an aromatase inhibitor for up to 5 years (total 7-8 years) is also supported 1

Duration Considerations

• Standard duration is 5 years, but extended therapy up to 10 years total may be considered for higher-risk features 1
• Extended aromatase inhibitor therapy carries ongoing risks and side effects that must be weighed against potential benefits 1

Critical Clinical Caveats

Tumor Characteristics That Modify Recommendations

• Patients with T1b tumors with low-grade histology and no lymphovascular invasion should receive endocrine monotherapy, as the TAILORx trial did not include such favorable tumors 1
• For tumors ≤0.5 cm and node-negative, consider adjuvant endocrine therapy alone (category 2B) regardless of recurrence score 1

When to Consider Chemotherapy Despite RS 16-25 in Postmenopausal Women

• The NCCN panel notes that clinical decision-making should incorporate tumor size, grade, lymphovascular invasion, and comorbid conditions beyond just the recurrence score 1
• Some real-world data suggest that among patients with RS 20-25 specifically, chemotherapy may provide an overall survival benefit regardless of age, though this contradicts the TAILORx findings 3

Node-Positive Disease Considerations

If the patient has 1-3 positive lymph nodes (not node-negative as in the original question), the treatment paradigm changes:

• For postmenopausal women with 1-3 positive nodes and RS ≤25, the RxPONDER trial showed no benefit from chemotherapy (5-year invasive disease-free survival 91.9% with endocrine alone vs 91.3% with chemoendocrine therapy; HR 1.02) 4
• For premenopausal women with 1-3 positive nodes and RS ≤25, chemotherapy provided significant benefit (5-year invasive disease-free survival 89.0% with endocrine alone vs 93.9% with chemoendocrine therapy; HR 0.60) 4

Monitoring and Adjunctive Therapies

• Consider adjuvant bisphosphonate therapy for 3-5 years in postmenopausal patients with high-risk features to reduce distant metastasis risk 1
• For select high-risk patients (≥4 nodes or 1-3 nodes with T3 tumors, grade 3, or Ki-67 ≥20%), consider adding abemaciclib for 2 years to endocrine therapy 1

Common Pitfalls to Avoid

• Do not withhold endocrine therapy based solely on the decision to omit chemotherapy—endocrine therapy is mandatory for all HR-positive breast cancer regardless of chemotherapy use 5
• Do not use concurrent tamoxifen with chemotherapy—if both are indicated, chemotherapy must be given first, followed by sequential endocrine therapy 1
• Do not extrapolate postmenopausal data to premenopausal women—the chemotherapy benefit differs significantly by menopausal status in the RS 16-25 range 2, 4