A Retrospective Analysis of Risk Factors of Central Nervous System Metastases in Operable Breast Cancer: Different Survival by Biological Subtype and Ki67 Overexpression.

Abstract

Abstract Background: New agents have improved systemic disease control, but the control of central nervous system (CNS) metastases is still insufficient. The identification of factors that may predispose to CNS metastases may help lead to earlier detection possibly to improvement in disease management.Methods: Patients (pts) with metastatic who were diagnosed with clinical stage I-III primary breast cancer at National Cancer Center Hospital East from January 2003 to December 2005 were screened. All pts with CNS metastases were identified by CT or MRI. Cox proportional hazards models were fitted to find risk factors of CNS metastases. Factors included age, menopausal status, clinical stage, T stage, histological grade, lymphovascular invasion, hormone and HER2 status, and Ki67 (at least 30% tumor cells positive). Survival was calculated by the Kaplan-Meier method.Results: Median follow-up from operation was 53.5 months. Of 591 breast cancer pts, 76 pts (12.9%) relapsed. Seventeen pts (2.9%) developed CNS metastases; 5 pts developed as the first recurrence site. Multivariable analysis indicated the higher risk for developing CNS metastases were triple negative (TN) tumors (HR 5.532, 95% CI 1.445-21.180, p=0.013) and Ki67 overexpression (HR 3.906, 95% CI 1.179-12.939, p=0.026). There were no statistically significant differences in other factors. CNS metastasesCumulative incidence of CNS metastases (4 yrs)Median duration to CNS metastases (Months)Overall survival (4 yrs)Disease free survival (4 yrs)TN9.7% (9/93 pts)9.4%11.378.5%73.3%HER2 positive3.7% (4/107 pts)4.4%20.391.0%84.9%Others1.0% (4/391 pts)0.8% (p<0.0001)24.197.5% (p<0.0001)92.4% (p<0.0001) Ki67 ≥30%8.6% (12/140 pts)9.4%12.382.4%75.0%Ki67 <30%1.1% (5/446 pts)0.7% (p<0.0001)23.996.7% (p<0.0001)92.0% (p<0.0001) Discussion: In our analysis, TN or Ki67 overexpression breast cancer showed earlier CNS metastases and shorter overall survival. In case of these tumors, there is higher probability for early detection of limited CNS metastatic involvement. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6053.