Long-Term Impact of Regional Nodal Irradiation in Patients With Node-Positive Breast Cancer Treated With Neoadjuvant Systemic Therapy.

Purpose: The impact of regional nodal irradiation (RNI) on locoregional recurrence (LRR) and any disease recurrence (DR) in women with node-positive breast cancer who receive neoadjuvant systemic therapy (NAT) is unknown.

Methods And Materials: The impact of RNI on LRR and DR was estimated with the cumulative incidence method in 1289 women with stage II to III breast cancer with cytologically confirmed axillary metastases who received NAT between 1989 and 2007. Multicovariate Cox regression analysis was performed to examine the effect of RNI after accounting for other predictive and prognostic variables.

Results: The median follow-up after definitive surgery was 10.2 years. Axillary pathologic complete response (pCR) was observed in 368 of 1289 patients (28.5%). On univariate analysis, axillary pCR reduced 10-year LRR risk from 9.7% to 4.8% (P = .006) and DR risk from 43.0% to 17.0% (P < .001). RNI was administered to 1080 of 1289 patients (83.8%). On univariate analysis, RNI did not affect 10-year LRR risk (no RNI, 9.4%; RNI, 8.1%; P = .62) or DR risk (no RNI, 31.3%; RNI, 36.5%; P = .16). On multicovariate analysis, RNI significantly reduced the risk of LRR (hazard ratio, 0.497; 95% confidence interval [CI], 0.279-0.884; P = .02) and DR (hazard ratio, 0.731; 95% CI, 0.541-0.988; P = .04) and showed a particularly strong reduction in risk of DR in patients with HER2+ disease who received trastuzumab (hazard ratio, 0.237; 95% CI, 0.109-0.517; P = .0003). A nomogram to predict 10-year LRR risk with and without RNI has been generated to assist clinicians in individualizing treatment decisions based on patient and disease characteristics and response to NAT.

Conclusions: Adjuvant RNI reduces risk of LRR and DR in patients with breast cancer with axillary metastases who receive NAT across subtypes and particularly decreases the risk of DR in HER2+ breast cancer treated with trastuzumab. Enrollment on the National Surgical Adjuvant Breast and Bowel Project B-51/Radiation Therapy Oncology Group 1304 protocol is encouraged to help determine whether RNI can be omitted in patients with axillary pCR to NAT.