A high number of tumor free axillary lymph nodes from patients with lymph node negative breast carcinoma is associated with poor outcome.

BACKGROUND Lymph node metastasis is the oldest and most reliable prognostic indicator in breast carcinoma. In the absence of tumor metastasis, draining lymph nodes can undergo hyperplasia, resulting in increases in the number and size of detectable lymph nodes. The prognostic value of this process has never been established. Lymph node negative breast carcinoma provides a unique opportunity to study the downstream effects of increased lymphatic drainage and lymph node hyperplasia. METHODS The authors studied 290 cases of lymph node negative breast carcinoma and provided patients with a median of 103 months of follow-up. The number of tumor free lymph nodes in ipsilateral axillary resections, as well as 10 traditional histopathologic markers, were analyzed for their prognostic value. RESULTS The cohort was divided into quartiles according to the number of tumor negative lymph nodes. The 5-year survival for patients with 20 or more tumor free lymph nodes (top quartile) was 84.7%, compared with 96.3% for patients with fewer than 20 tumor free lymph nodes. The 5-year relative risk of dying of metastatic disease in the top quartile was 3.61 (95% confidence interval, 1.37-9.52, P = 0.01), independent of necrosis, tumor size, patient age, nuclear and histologic grade, lymphocytic infiltrate, and lymphovascular invasion. The absolute lymph node number was highly associated with the presence of necrosis in invasive tumor. CONCLUSIONS The number of tumor free lymph nodes is a novel, independent predictor of aggressive disease in cases of lymph node negative breast carcinoma. This finding may be a biologic function of host-derived, and possibly tumor-derived, lymphangiogenic cytokines.