INTRODUCTION: Estrogen receptor (ER) status is a critical component of determining initial therapy of newly diagnosed breast cancer. Although 70% of primary breast malignancies are ER+, there remains limited data on whether ER status influences treatment outcomes for patients with brain metastases. Gamma Knife Radiosurgery (GKS) is increasingly being used in the management of brain metastases. The goal of this study is to determine the impact of ER status in patients receiving GKS for breast cancer metastases to brain. METHODS: A database of consecutive breast cancer patients receiving GKS at our institution from January 2000 to March 2012 was reviewed for hormone receptor status, dates of initial brain metastasis and GKS, presence of neurologic symptoms, and recurrence of GKS-treated lesions. The main cohort was subdivided by receptor status at initial tissue diagnosis. Progression or loss of local control of the treated lesions was defined as radiographic evidence of growth (greater than 20% increase in the sum of the longest diameters) or treated lesions requiring additional treatment until death or last follow-up. Analysis for neurological symptom improvement was performed for patients with available follow-up information, with at least 1 month follow–up. Comparisons were made between subgroups using Kaplan-Meier method, Chi-square analysis and univariate comparisons with log-rank test. Significance was set at p < 0.05. RESULTS: A total of 93 breast cancer patients received GKS, and receptor status was available in 83 patients. Forty-six (45.7%) percent of patients were ER+. The median follow-up for all patients was 85.5 months (range 2.5 to 307.6). For all patients, the median number of brain metastases was 2.0 and median age at diagnosis was 54 years. According to ER status, there were no differences in patient age at diagnosis, age at GKS, or number of brain metastasis, although the time to development of brain metastasis (median 92.2 vs 34.0 months, p = 0.02) was longer in the ER+ cohort. The median GKS dose was 18 Gy. Fifty one percent of ER+ patients had GKS alone versus 54% of ER− patients (p = 0.26). There was no difference in survival from GKS according to ER status, with survival for ER+ and ER− patients of 21.3 and 16.8 months, respectively (p = 0.39). However, ER+ patients exhibited longer progression-free survival of treated metastases with 19.1 versus 7.5 months (p = 0.02). In addition, for all patients who attained local control, 10 of 22 ER+ patients had an improvement in neurologic symptoms versus 4 of 17 ER− patients (p = 0.02). DISCUSSION: While ER positivity conveys a favorable prognosis at the time of diagnosis, survival after intensive treatment of brain metastases appears similar to ER− patients. This occurs independently of ER status, even though brain relapse was significantly more common in ER− patients, suggesting efforts to further improve extracranial systemic control may potentially enhance survival. Both local and neurologic symptom control were poorer for ER− patients. Whether alternative approaches, such as increasing GKS dose, surgical resection, and/or routine inclusion of WBRT, can improve outcomes for ER− patients with brain metastases may warrant future investigation. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-12-02.

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