Factors influencing the outcome of breast cancer patients with 10 or more metastasized axillary lymph nodes

Background: The purpose of this study was to investigate prognostic factors in breast cancer patients with metastasis of ten or more lymph nodes (pathologic N3a). Methods: We conducted a retrospective analysis of the cases of 304 breast cancer patients with pathologic N3a disease who had undergone definitive surgery between 1986 and 2006, and investigated the correlation between clinicopathologic characteristics and treatment outcomes. Results: With a median follow-up period of 55 months, the 5-year disease-free survival rate was 42.9% and the overall survival rate was 57.8%. Univariate analysis showed that the factors associated with poor disease-free survival were: age < 35 years (P = 0.001), history of neoadjuvant chemotherapy (P<0.001), T4 stage (P<0.001), 20 or more positive lymph nodes (P<0.001), presence of lymphovascular invasion (P = 0.003), and negative progesterone receptor expression (P = 0.003). Multivariate analysis showed the factors with independent prognostic significance to be: history of neoadjuvant chemotherapy (hazard ratio [HR] 3.163; 95% confidence interval [CI], 2.025-4.941; P<0.001), 20 or more positive nodes (HR 1.598; 95% CI, 1.063-2.402; P = 0.024), and presence of lymphovascular invasion (HR 1.636; 95% CI, 1.009-2.654; P = 0.046). Factors associated with poor overall survival in univariate analysis were: age <35 years (P = 0.033), history of neoadjuvant chemotherapy (P<0.001), T4 stage (P = 0.001), 20 or more positive lymph nodes (P<0.001), and negative progesterone receptor expression (P = 0.013). Multivariate analysis showed these factors to be: history of neoadjuvant chemotherapy (HR 2.900; 95% CI, 2.011-4.182; P<0.001), and 20 or more positive nodes (HR 1.956; 95% CI, 1.419-2.696; P<0.001). Conclusion: Cases of breast tumors with extensive nodal metastasis were found to be heterogeneous in terms of prognosis. History of previous neoadjuvant chemotherapy and higher numbers of metastatic lymph nodes were found to be the two most important prognostic markers for pathologic N3a disease. New strategies such as biologic therapy and novel combinations should be considered for application in patients with poor prognosis, rather than conventional treatment.