The Prognostic Significance of Micrometastases in Breast Cancer: a SEER Population-based Analysis

Introduction: The prognostic significance of lymph node micrometastases in breast cancer is controversial. We hypothesized that the survival of patients with solely micrometastatic disease (N1mi) would be intermediate to patients with 1-3 tumor-positive lymph nodes (N1) and those with no positive lymph nodes (N0).

Methods: We queried the surveillance, epidemiology and end results (SEER) database for all patients between 1992 and 2003 with invasive ductal or lobular breast cancer without distant metastases and < or = 3 axillary nodes with macroscopic disease. Patients were stratified by nodal involvement and compared using the Kaplan-Meier method. Cox proportional hazards regression was utilized to compare survival after adjusting for patient and tumor characteristics.

Results: Between 1992 and 2003, N1mi diagnoses increased from 2.3% to 7% among the 209,720 study patients (p < 0.001). In a T-stage stratified univariate analysis, N1mi patients had a worse prognosis in T2 lesions. On multivariate analysis, N1mi remained a significant prognostic indicator across all patients (p < 0.0001) with a hazard ratio of 1.35 compared to N0 disease and 0.82 compared to N1 disease. Other negative prognostic factors included male gender, estrogen-receptor negativity, progesterone-receptor negativity, lobular histology, higher grade, older age, higher T-stage, and diagnosis in an earlier time period.

Conclusion: Nodal micrometastasis of breast cancer carries a prognosis intermediate to N0 and N1 disease, even after adjusting for tumor- and patient-related factors. Prospective study is warranted and the results of pending trials are highly anticipated. Until then adjuvant therapy trials should consider using N1mi as a stratification factor when determining nodal status.