Is it safe to omit regional nodal irradiation (RNI) in breast cancer patients who have responded to neo-adjuvant chemotherapy (NAC)?

Regional Nodal Irradiation After Response to Neoadjuvant Chemotherapy in Breast Cancer

Regional nodal irradiation (RNI) should be based on pre-chemotherapy tumor characteristics, regardless of response to neoadjuvant chemotherapy (NAC), as radiation therapy is recommended in patients with clinical stage III disease even with a pathologic complete response to NAC. 1

Decision-Making for Regional Nodal Irradiation

Pre-Chemotherapy Nodal Status Guides Treatment

• Decisions about RNI should be made based on pre-chemotherapy tumor characteristics, not on the response to NAC 1
• For patients with clinical stage III disease who achieve pathologic complete response to NAC, radiation therapy is still recommended 1

Recommendations Based on Nodal Status

• 4 or more positive lymph nodes: RNI is strongly recommended (category 1) after lumpectomy or mastectomy 1
• 1-3 positive lymph nodes: Strongly consider RNI based on risk assessment after lumpectomy or mastectomy 1
• RNI includes treatment of the supraclavicular area, infraclavicular region, internal mammary nodes, and any part of the axillary bed considered at risk 1

Evidence Supporting RNI After NAC

Benefits of RNI in Node-Positive Disease

• The NCIC-CTG MA.20 trial demonstrated that regional node irradiation reduces the risk of locoregional and distant recurrence and improves disease-free survival in node-positive patients 1
• After 10 years of median follow-up, regional nodal irradiation improved locoregional disease-free survival, distant disease-free survival, and breast cancer mortality 1
• Multicovariate analysis shows RNI significantly reduces the risk of locoregional recurrence and any disease recurrence in patients with axillary metastases who received NAC 2

Recent Research on RNI Omission

• The NSABP B-51/RTOG 1304 trial (2025) found that in patients who achieved ypN0 status (pathologically negative nodes) after NAC, omitting RNI did not significantly increase the risk of invasive breast cancer recurrence or death 3
• After a median follow-up of 59.5 months, there was no significant difference in invasive breast cancer recurrence-free interval between patients who received RNI and those who did not (hazard ratio, 0.88; 95% CI, 0.60 to 1.28) 3

Special Considerations

Subtype-Specific Effects

• RNI shows particularly strong reduction in risk of disease recurrence in patients with HER2+ disease who received trastuzumab 2
• Treatment decisions should consider breast cancer subtype and other risk factors 2

Potential Toxicities

• When administering RNI, CT-based treatment planning should be used to reduce radiation dose to the heart and lungs 1
• Grade 4 adverse events are rare with RNI (0.5% in the irradiation group vs 0.1% in the no-irradiation group) 3

Clinical Approach

Algorithm for Decision-Making

1. Determine pre-chemotherapy nodal status and tumor characteristics
2. Assess pathologic response to NAC
3. For patients with initial node-positive disease:
   • If 4+ positive nodes pre-NAC: Recommend RNI regardless of response 1
   • If 1-3 positive nodes pre-NAC: Strongly consider RNI based on risk factors 1
   • For patients achieving ypN0 status after NAC: Consider the option of omitting RNI based on recent evidence 3, 4

Radiation Fields

• When RNI is indicated, treatment should include the supraclavicular area, infraclavicular region, internal mammary nodes, and any part of the axillary bed considered at risk 1
• The recommended radiation dose for chest wall/breast is 45-50 Gy in fractions of 1.8-2.0 Gy, or 42.5 Gy in fractions of 2.55 Gy 1

While recent evidence suggests RNI may be safely omitted in patients who achieve ypN0 status after NAC 3, 4, current guidelines still recommend basing radiation therapy decisions on pre-chemotherapy tumor characteristics 1. This approach ensures comprehensive treatment of patients with initially node-positive disease, which has been shown to improve locoregional control and disease-free survival.