Identifying breast cancer patients at risk for Central Nervous System (CNS) metastases in trials of the International Breast Cancer Study Group (IBCSG)

Background: We sought to determine whether a high-risk group could be defined among patients with operable breast cancer in whom a search of occult central nervous system (CNS) metastases was justified. Patients and methods: We evaluated data from 9524 women with early breast cancer (42% node-negative) who were randomized in International Breast Cancer Study Group clinical trials between 1978 and 1999, and treated without anthracyclines, taxanes, or trastuzumab. We identified patients whose site of first event was CNS and those who had a CNS event at any time. Results: Median follow-up was 13 years. The 10-year incidence (10-yr) of CNS relapse was 5.2% (1.3% as first recurrence). Factors predictive of CNS as first recurrence included: node-positive disease (10-yr = 2.2% for > 3 N+), estrogen receptor-negative (2.3%), tumor size > 2 cm (1.7%), tumor grade 3 (2.0%), < 35 years old (2.2%), HER2-positive (2.7%), and estrogen receptor-negative and node-positive (2.6%). The risk of subsequent CNS recurrence was elevated in patients experiencing lung metastases (10-yr = 16.4%). Conclusion: Based on this large cohort we were able to define risk factors for CNS metastases, but could not define a group at sufficient risk to justify routine screening for occult CNS metastases.