Abstract PS2-03-29: Evaluating Prognosis According to Axillary Surgery in Breast Cancer Patients with Isolated Internal Mammary Lymph Node Metastasis (cN2b): A Retrospective Cohort Study

Abstract Background: Metastasis to the internal mammary lymph nodes (IMLN) plays a critical role in the regional staging and prognosis of breast cancer. Although IMLN involvement often occurs alongside axillary lymph node (AXLN) metastasis, isolated IMLN metastasis without axillary involvement (cN2b) is rare, and the optimal surgical approach for these patients remains uncertain. While axillary lymph node dissection (ALND) is generally recommended for node-positive disease, its necessity in cases of cN2b is debatable. This study aims to clarify the prognostic significance of AXLN status and to assess whether ALND can be safely omitted in breast cancer patients presenting with isolated IMLN metastasis. Methods: We retrospectively analyzed patients with IMLN metastases confirmed preoperatively by cytology, who underwent surgery at our institution between 2007 and 2021. Inclusion required cytological confirmation of IMLN metastasis. Exclusion criteria included clinical T4 tumors, supraclavicular or distant metastases, and bilateral breast cancer. Patients were stratified into two groups: cN2b (isolated IMLN metastasis, n=21) and cN3b (IMLN with AXLN metastasis, n=104). Clinicopathological characteristics and 5-year disease-free survival (DFS) were compared between groups. In the cN2b cohort, oncologic outcomes were further evaluated according to the type of axillary surgery performed: sentinel lymph node biopsy (SLNB) alone versus ALND. Results: Of 15,231 surgically treated breast cancer patients, 230 had IMLN metastasis. After exclusions, 125 (0.8%) were included: 21 (0.1%) with cN2b and 104 (0.7%) with cN3b. The median follow-up was 59 months. The cN2b group demonstrated a significantly higher frequency of medial tumor location (52% vs. 30%, p=0.046) and tended to present with smaller tumor size compared to the cN3b group (p=0.039). Histologically, invasive ductal carcinoma was the predominant subtype in both groups. Hormone receptor-positive tumors accounted for the majority of cases in both cN2b and cN3b groups (62% and 60%, respectively, p=0.85). HER2-positive tumors were seen in 19% of cN2b and 26% of cN3b cases (p=0.50). The 5-year DFS was significantly better in cN2b patients compared to cN3b (94.7% vs. 64.0%, p=0.0049), indicating favorable prognosis in the absence of axillary involvement. Among cN2b patients, 10 underwent SLNB alone and 10 underwent ALND. The remaining patient did not undergo any axillary surgery due to personal preference. DFS rates did not significantly differ between these subgroups (88.9% for SLNB vs. 100% for ALND, p=0.32). In the cN2b group, 20 patients (95.2%), and in the cN3b group, 101 patients (97.1%) received postoperative radiotherapy, with irradiation fields including the regional lymph node areas in all cases. One SLNB-only patient developed distant bone metastasis, but no regional axillary recurrence occurred in any group. Two ALND patients had previously undetected axillary metastases though it is unclear whether these findings had any effect on DFS. Conclusions: This study suggests that breast cancer patients with isolated IMLN metastasis and no axillary involvement (cN2b) have significantly better outcomes than those with combined IMLN and AXLN metastasis (cN3b). Furthermore, omission of ALND in cN2b cases may be feasible and did not appear to compromise disease control, with no locoregional failures observed in the SLNB-only group. These findings support the potential safety and efficacy of a less invasive axillary management strategy—SLNB alone—for appropriately selected cN2b patients. Considering the rarity of this clinical subset, larger prospective studies are warranted to further validate these findings and refine treatment guidelines for isolated IMLN metastasis. Citation Format: Y. Ishizaka, T. Sakai, M. Kasahara, M. Kai, A. Kanazawa, E. Taniguchi, Y. Ito, Y. Kimura, U. Nakadaira, Y. Inoue, T. Maeda, N. Yamashita, A. Kataoka, N. Uehiro, T. Ueno. Evaluating Prognosis According to Axillary Surgery in Breast Cancer Patients with Isolated Internal Mammary Lymph Node Metastasis (cN2b): A Retrospective Cohort Study abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-03-29.