Background: The number of involved lymph nodes negatively affects prognosis in breast cancer patients. Nevertheless, current staging and treatment recommendations do not distinguish between patients with single versus multiple lymphatic micrometastases. In this study, we aim to better characterize these patients. Methods: The National Cancer Database was retrospectively queried to identify 486,800 women with stage I–III, estrogen receptor-positive/progesterone receptor-positive/human epidermal growth factor receptor 2-negative (ER+/PR+/HER2−) breast cancer and nodal status of N0, N1mi with 1 (Nmic1) or more (Nmic > 1) involved nodes, and N1 with 1 involved node (N1.1), from 2010 to 2016. Patients with different nodal statuses were compared regarding treatment characteristics, survival, and benefit from chemotherapy by their 21-gene recurrence score (RS). Results: Of the 23,072 N1mi patients, 88.3% were Nmic1 and 11.7% were Nmic > 1. Nmic > 1 patients were younger, had larger and higher-grade tumors, with more lymphovascular invasion, and were more commonly treated by axillary dissection, radiation, and chemotherapy than Nmic1 patients. In that, they were comparable with N1.1 patients. Five-year survival of Nmic > 1 patients (88.1%) was worse than Nmic1 patients (90.1%; p = 0.02), but similar to N1.1 patients (87.9%). Nmic1, Nmic > 1, and N1.1 patients with RS 11–25 exhibited a < 2% absolute survival benefit associated with chemotherapy. With RS > 25, Nmic > 1 patients showed a 3.5% benefit, similar to Nmic1 (4.8%) and lower than N1.1 (10.9%) patients. Conclusions: Nmic > 1 breast cancer patients have worse prognoses than Nmic1 patients, similar to N1.1 patients. Our data suggest those patients with RS 11–25 have minimal benefit from chemotherapy. These findings should be taken into account when discussing prognosis and considering chemotherapy in patients with lymphatic micrometastases.
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