Abstract Background: Brain metastases (BM) occur in 10%-15% patients of breast cancer patients. It is associated with poor prognosis, requiring great effort to manage local and systemic treatment for BM. The purpose of this study was to analyze the clinico-pathological characteristics of long-term survivors with BM in breast cancer patients. Method: 63 patients with breast cancer BM diagnosed from 2002 to 2010 at the Tokyo Metropolitan Komagome hospital were included. Long–term survival group (Long) was defined as to be consisted of the patients with survival duration more than 36 months after diagnosed with BM and the patients with less than 36 month was into Short-term survival group (Short) in this study. The clinico-pathological characteristics were compared between these two groups. Survival rate and prognostic factors of BM were analyzed by the Kaplan–Meier method and employed by Log–Rank test. Multivariate analysis was performed by the Cox proportional hazard model. Results: Median age of the 63 patients was 53 years (range, 35–78). Median survival time after BM was 12 months (range, 1–168), with about 90 percent of cause of death related to BM (e.g. failure of PS due to BM). As for ER and HER2 status, the number of ER+/HER2- (Luminal:Lum), ER+or-/HER2+ (HER2-enrich:Her2-E), ER-/HER2- (Basal:Bas) were 18, 27, 18, respectively. Among those 63 patients, 11 survived 36 months or more after BM. However, there was no difference in the rate of ER status between Long (55%) and Short (38%), there were significantly high rate of Her2-E case in Long (73%) as compared with Short (29%). Median survival duration after diagnosed with BM of Lum, Her2-E and Bas were 11, 37, 3 months, respectively. Prognosis of Bas was significantly poor (Bas vs. Her2-E p<0.001), and although Her2-E was not significant as compared with ER (p = 0.188), survival time after BM of Her2-E was the tendency to be long. In univariate analysis, Karnofsky performance status (KPS≥70 or <70), HER2 status, disease free interval (from initial diagnosis to first recurrence, DFI≥2years or <2years) had significant impact on survival time after BM. (p = 0.0458, 0.0398, 0.0385, respectively). Meningitis status was a borderline. (p = 0.052) In multivariate analysis, KPS, HER2 status and DFI were significant prognostic factors. (KPS: RR 2.08, 95% CI 1.08-4.07; HER2: RR 2.911, 95% CI 1.396- 6.484; DFI: RR 1.933, 95% CI 0.83-4.102) Conclusions: Although, it was believed that the prognosis after BM was poor, Her2-E BM had a comparatively good prognosis. An existing report supports extension of the survival time after BM by HER2–targeted treatment in BM cases with Her2 positive breast cancer. This newest study reviles the median survival after BM as 37 months in Her2-E BM group, but that of Bas group was only 3 months and this is not improved at all compared with historically reported survival duration (2.4-4.9months). Our reports suggested that the innovation of Her2–targeted treatment leads this surprising improvement of life extension in HER2 positive BM patients but innovation of cytotoxic agents could not contribute toward improvement of clinical outcome in triple negative BM patients. So the necessity of examining the medical treatment of breast cancer BM according to subtype from now on is also considered. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-11-11.