The aim of this retrospective analysis was to investigate the factors affecting the prognosis of brain metastases in breast cancer patients to identify subgroups which might benefit from prophylactic treatments in future. Seventy-three early and 13 advanced stage patients with known Erb-2 status were included. In 14% of the early stage patients, the first recurrence site was isolated brain metastasis. None of the anthracycline resistant patients had brain metastases as their first recurrence site. The median interval between diagnosis and brain metastasis was 41.5 months (95% CI, 35.79-47.20) in early stage patients. The median interval between the first extracerebral metastases to the brain metastases was 15.5 months (95% CI, 12.24-18.76) in all patients. High histologic and nuclear grade, large tumor, anthracycline resistance were the factors which significantly affected the early appearance of brain metastases but only advanced age (>= 55 years, P = .035) correlated with isolated brain metastasis. Progression with isolated brain metastases was significantly higher in responsive ErbB-2 positive population (P = .036) and none of other pathological factors was associated with isolated brain metastasis in advanced stage. The median survival after brain metastasis in patients with brain metastasis as first recurrence was longer than the patients with brain metastasis after other organ metastasis (13 months vs 2 months P = .003). The median survival following brain metastases in complete responsive patients was higher than the others (24 months vs 6 months, P = .002). Therefore, response to systemic treatment was more determinative in the development of isolated brain metastases than clinical and pathologic features. ErbB-2 should be emphasized in prophylactic treatment strategies. Prophylactic cranial radiotherapy may be an effective treatment option for metastatic patients with complete responsive disease and with controlled ErbB-2 positive disease. (C) 2008 Elsevier Ltd. All rights reserved.