2876 - Genomically-Guided Regional Nodal Irradiation in Luminal Breast Cancer Using MammaPrint

Purpose/Objective(s): Randomized trials support regional nodal irradiation (RNI) for node-positive breast cancer, though benefit may vary in hormone receptor–positive (HR+) disease treated with modern systemic therapy. Genomic assays such as MammaPrint (MP) provide prognostic stratification for chemotherapy, but their ability to identify patients who benefit from RT remains unclear. We hypothesized that MP genomic risk may stratify clinical outcomes after RT and RNI.

Materials/Methods: We performed a single-institution retrospective review of all patients with HR+, HER2-negative, T1–2 N1 or T3 N0 breast cancer diagnosed from 2012-2023, with MP testing, who received adjuvant RT. MP risk was classified as low or high using standard thresholds. Patients were classified as receiving RNI vs breast/chest wall RT alone. Outcomes included overall survival (OS), disease-free survival (DFS), distant disease-free survival (DDFS), local recurrence–free survival (LRFS), and locoregional recurrence–free survival (LRRFS). Survival was assessed using Kaplan–Meier methods, log-rank testing, and univariable Cox regression, stratified by MP risk.

Results: A total of 179 patients were included; 107 (59.8%) were low-risk and 72 (40.2%) high-risk. The overall rates of locoregional recurrence, distant metastasis, and mortality were 2.8% (5/179), 3.4% (6/179), and 7.8% (14/179) of patients, respectively. Median follow-up was 73.6 months (range: 6.5–153.6 months); median survival was not reached for any endpoint. The high-risk group did not significantly differ from the low-risk group (reference group) in terms of OS (HR 0.48; 95% CI 0.13-1.72, p=0.257), DFS (HR 0.93; 95% CI 0.37-2.33, p=0.881), DDFS (HR 0.89; 95% CI 0.33-2.40, p=0.824), LRFS (HR 0.59; 95% CI 0.19-1.83, p=0.359), or LRRFS (HR 0.86; 95% CI 0.32-2.28, p=0.763). RNI was delivered to 122 patients (68.2%): 54 (44.3%) high-risk and 68 (55.7%) low-risk. Although not statistically significant, RNI trended towards improved outcomes across endpoints for low-risk patients (Table 1). This pattern was not observed in the high-risk cohort.

Conclusion: In this contemporary luminal breast cancer cohort, MP genomic risk did not identify a subgroup with a statistically significant benefit from RT or RNI. Although outcomes favored RNI among MP low-risk patients non-significantly, this pattern was not observed in high-risk patients, likely reflecting limited sample size and event rates. Further study on clinical trial is warranted.