Occult Micrometastases in Axillary Lymph Nodes Predict Subsequent Distant Metastases in Stage I Breast Cancer: A Case-Control Study with 15-Year Follow-Up

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Abstract
The prognostic significance of occult axillary metastases was evaluated in patients with stage I breast cancer. Ninety-six patients with pT1 breast carcinoma who underwent axillary lymph node dissection had negative nodes in routine microscopic examination. Forty-eight patients developed distant metastases within 15 years after surgery (M group) and are compared to 48 age-matched patients who were disease-free for 15 years (NM group). We reexamined 1539 lymph nodes from these patients, using three levels and cytokeratin immunostain. Occult metastases were detected in 21 patients: 16 of 48 (34%) in the M group and 5 of 48 (11%) in the NM group (P = .007). All metastases measured 2.0 mm or less and were classified as micrometastases (>0.2 mm to 2.0 mm) in 11 cases and as individual tumor cells (individual cells or clusters measuring ≤0.2 mm) in 10 cases. Micrometastases were 10 times more frequent in the M group than in the NM group (10/48 vs. 1/48; P = .004). Although there was no difference in tumor size, histologic type, estrogen receptor status, or type of treatment between the two patient groups, tumors in the M group were of a higher grade, had higher mitotic index and showed lymphovascular invasion. In multiple logistic regression, only high mitotic index and presence of micrometastases showed an independent significant correlation with the subsequent occurrence of distant metastases. The presence of micrometastases (>0.2 to 2.0 mm) in axillary nodes is significantly associated with the development of distant metastases in patients with T1 breast cancer.