Isolated Regional Nodal Recurrence after Primary Breast Cancer: Risk Factors and Survival by Mode of Detection

Purpose:The prognostic relevance of the detection mode for regional lymph node recurrence (LNR) remains unclear.We aimed to identify the risk factors associated with isolated regional LNR and to evaluate the impact of the mode of detection on distant metastasis-free survival (DMFS) and overall survival (OS).Methods: This retrospective cohort study included women who underwent surgery for stage I-III invasive breast cancer between January 2011 and December 2019, with follow-up until December 2024.Isolated regional LNR was categorized according to the detection method (imaging vs. symptoms).Risk factors were identified using the Fine-Gray sub-distribution hazard model, and DMFS and OS were compared using Kaplan-Meier analysis and log-rank tests.Results: Among 13,406 women (median age, 49 years; range, 20-87 years), 126 (0.9%) developed isolated regional LNR during a median follow-up of 6.3 years.Of these, 118 (93.7%) were detected through imaging and 8 (6.3%) through symptoms.Independent risk factors for isolated regional LNR included higher T stages (T2: hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.11-2.64;T3: HR, 3.08; 95% CI, 1.68-5.65),higher N stages (N2: HR, 2.97; 95% CI, 1.54-5.75;N3: HR, 3.12; 95% CI, 1.36-7.13),triple-negative subtype (HR, 1.71; 95% CI, 1.09-2.67),and omission of adjuvant radiotherapy (HR, 4.35; 95% CI, 2.86-6.67).Radiological patterns varied by detection, with ultrasound usually detecting level I nodes (51.6%) and computed tomography detecting internal mammary nodes (58.1%).Symptom-detected recurrence frequently occurred in the supraclavicular region (50.0%).Symptom-detected LNRs were associated with significantly worse DMFS (p <0.05) than imaging-detected LNRs; however, OS did not differ between the groups. Conclusion:The detection mode was associated with DMFS, but not OS, suggesting that long-term outcomes are driven more by disease biology than by how recurrence is detected.