Predicting Brain Metastasis in Breast Cancer Patients: Stage Versus Biology

Brain metastasis is a devastating complication of breast cancer. We conducted a retrospective analysis among patients presenting with early and metastatic breast cancer to determine the clinical and pathological factors that can predict brain metastasis. Advanced stage and HER2 overexpression were the major predictive factors of brain metastasis in the early setting while lung metastasis and early relapse were associated with subsequent brain metastasis in the metastatic setting. Background: Brain metastasis (BM) is a life-threatening event in breast cancer patients. Identifying patients at a high risk for BM can help to adopt screening programs and test preventive interventions. We tried to identify the incidence of BM in different stages and subtypes of breast cancer. Patients and Methods: We reviewed the clinical records of 2193 consecutive breast cancer patients who presented between January 1999 and December 2010. We explored the incidence of BM in relation to standard clinicopathological factors, and determined the cumulative risk of BM according to the disease stage and phenotype. Results: Of the 2193 included women, 160 (7.3%) developed BM at a median follow-up of 5.8 years. Age younger than 60 years (P =.015), larger tumors (P =.004), lymph node (LN) positivity (P <.001), high tumor grade (P =.012), and HER2 positivity (P <.001) were associated with higher incidence of BM in the whole population. In patients who presented with locoregional disease, 3 factors independently predicted BM: large tumors (hazard ratio [HR], 3.60; 95% confidence interval [CI], 1.54-8.38; P =.003), axillary LN metastasis (HR, 4.03; 95% CI, 1.91-8.52; P <.001), and HER2 positivity (HR, 1.89; 95% CI, 1.0-3.41; P =.049). A Brain Relapse Index was formulated using those 3 factors, with 5-year cumulative incidence of BM of 19.2% in those having the 2 or 3 risk factors versus 2.5% in those with no or 1 risk factor (P <.001). In metastatic patients, 3 factors were associated with higher risk of BM: HER2 positivity (P =.007), shorter relapse-free interval (P <.001), and lung metastasis (P <.001). Conclusion: Disease stage and biological subtypes predict the risk for BM and subsequent treatment outcome.