Regional Nodal Irradiation for cT3N0 HER2+ Breast Cancer with Pathologic Complete Response
For a patient with clinical T3N0 HER2-positive breast cancer who achieved pathologic complete response (pCR) after neoadjuvant chemotherapy, regional nodal irradiation (RNI) should be administered based on the pre-treatment clinical stage, as current guidelines mandate that radiation decisions be guided by the maximal disease stage at diagnosis regardless of treatment response. 1, 2
Guideline-Based Rationale
The NCCN explicitly states that following neoadjuvant chemotherapy, indications for radiation therapy should be guided by maximal disease stage from either pre-chemotherapy tumor characteristics at diagnosis or postchemotherapy pathology results—whichever is worse. 1 This principle does not negate the need for radiation therapy if indications were present at diagnosis. 1
For clinical T3 disease (tumors >5 cm), RNI is strongly recommended even in the setting of clinically node-negative disease. 1 The NCCN guidelines specifically recommend consideration of radiation to the ipsilateral supraclavicular area and internal mammary lymph nodes for patients with tumors greater than 5 cm. 1
Evidence Supporting RNI Despite pCR
Guideline Consensus
Clinical stage III disease warrants radiation therapy even with pathologic complete response to neoadjuvant chemotherapy. 2 The NCCN explicitly recommends that patients with clinical stage III disease who achieve pCR should still receive radiation therapy. 2
RNI should be strongly considered for select patients with node-negative disease at high risk, with clinicians assessing tumor size, lymphovascular invasion, response to neoadjuvant chemotherapy, extent of residual disease, and intrinsic tumor type. 1
Recent High-Quality Research Evidence
The most recent and highest-quality evidence comes from the NSABP B-51/RTOG 1304 trial (2025), which specifically addressed this question. 3 However, this landmark trial studied patients with initially node-positive disease (cN1) who converted to ypN0 after neoadjuvant chemotherapy—not patients who were clinically node-negative at presentation. 3 The trial found no benefit to RNI in the ypN0 population after neoadjuvant chemotherapy. 3
Critically, your patient differs from the B-51 population: they were clinically N0 at diagnosis, not cN1 converting to ypN0. The B-51 results cannot be directly extrapolated to your cT3N0 patient.
Supporting Evidence for RNI in Your Clinical Scenario
A 2018 retrospective analysis of 1,289 patients with initially node-positive breast cancer receiving neoadjuvant therapy found that RNI significantly reduced locoregional recurrence (HR 0.497,95% CI 0.279-0.884, P=0.02) and any disease recurrence (HR 0.731,95% CI 0.541-0.988, P=0.04) on multivariate analysis. 4 Notably, RNI showed particularly strong reduction in disease recurrence risk in HER2+ patients who received trastuzumab (HR 0.237,95% CI 0.109-0.517, P=0.0003). 4
Clinical Algorithm for Your Patient
Step 1: Establish Pre-Treatment Risk Category
- Clinical T3 (>5 cm) = High-risk feature for locoregional recurrence 1
- Clinical N0 status = Lower nodal risk but does not eliminate T3-associated risk 1
Step 2: Apply Guideline Recommendations
- NCCN Category 2A recommendation: Consider RNI for node-negative disease with tumors >5 cm 1
- Base radiation decisions on pre-treatment clinical stage, not post-chemotherapy pathology 1, 2
Step 3: Consider HER2+ Biology
- HER2+ subtype with trastuzumab shows exceptional benefit from RNI in reducing disease recurrence 4
- pCR in HER2+ disease indicates excellent systemic control but does not eliminate locoregional risk from initial T3 presentation 4
Step 4: Define RNI Target Volumes
- Supraclavicular area
- Infraclavicular region
- Internal mammary nodes
- Any part of the axillary bed considered at risk
Critical Caveats
The absence of level I evidence specifically for cT3N0 patients with pCR creates uncertainty. 1 The NCCN acknowledges that studies evaluating regional node management after neoadjuvant chemotherapy (NSABP B-51/RTOG 1304 and Alliance 011202) were ongoing at the time of their recommendations. 1 The B-51 trial has now reported, but studied a different population (cN1→ypN0). 3
Common pitfall: Assuming pCR eliminates the need for radiation based on post-treatment pathology alone. Guidelines consistently emphasize using the worst stage from either pre-treatment or post-treatment assessment. 1, 2
Recurrence risk may be lower for patients who experience pathologic complete response, 1 but the initial T3 presentation establishes a high-risk category that warrants comprehensive locoregional treatment. 1