Prognostic Significance of Nodal Burden According to ABO Blood Group in Stage II–III Breast Cancer: An Exploratory Analysis

Background/Objectives: Previous studies of ABO blood group and breast cancer prognosis have yielded inconsistent results, mainly evaluating blood group itself as a prognostic factor. We investigated whether the prognostic associations of clinicopathological factors differ according to ABO blood group in stage II–III breast cancer. Methods: We retrospectively analyzed 1540 patients with stage II–III breast cancer who underwent curative resection between 2010 and 2019. Blood group-specific prognostic analyses of breast cancer-specific survival (BCSS) were performed, with continuous variables analyzed without dichotomization. Based on the observed patterns, an exploratory interaction between blood group B and pathological nodal status was tested, and its robustness was assessed using a permutation test and sensitivity analyses. Results: ABO blood group was not associated with BCSS overall (p = 0.641). In blood group-stratified multivariable analyses, ≥4 lymph node metastases was an independent adverse prognostic factor in blood groups A, O, and AB, but not in blood group B. A significant interaction was observed between blood group B and pathological nodal status (0–3 vs. ≥4 nodes) (p for interaction < 0.001; permutation-adjusted p = 0.004). Among patients with 0–3 lymph node metastases, blood group B was independently associated with worse BCSS (hazard ratio, 2.04; 95% confidence interval, 1.25–3.32; p = 0.004), consistently across sensitivity analyses; this association was more evident among patients who received neoadjuvant chemotherapy. In this subgroup, blood group B was also associated with more distant and visceral recurrence (all p < 0.05). Conclusions: The prognostic association of nodal burden in stage II–III breast cancer may differ according to ABO blood group. The exploratory findings in patients with limited nodal involvement suggest that blood group B may identify a subgroup characterized by worse BCSS and increased distant and visceral recurrence. Given the small number of events in blood group B with ≥4 nodes and possible differences according to neoadjuvant chemotherapy, these findings are hypothesis-generating and warrant independent validation.