Abstract Background: The annexin superfamily of proteins has been implicated in several cellular processes. In particular, annexin A1 is known to have anti-inflammatory, anti-proliferative and pro-apoptotic functions. The expression and precise role of annexin A1 in breast cancer have been conflicting. The goal of this retrospective study was to explore the association of annexin A1 expression and survival outcome among women with breast cancer. Methods: 426 women with breast cancer whose tumor samples and associated data was available were identified. Annexin A1 expression was measured using RPPA and was considered as a categorical and continuous variable. Range of annexin A1 levels for the cohort was −1.90 to 2.36. Patients were divided into four groups according to the annexin A1 level: a) negative (annexin A1 <-0.84), b) low (annexin A1 > = −0.84 and <0.23), c) medium (annexin A1 >=0.23 and < 1.29) and d) high (annexin A1 >=1.29). Recurrence free survival (RFS) was estimated using the Kaplan-Meier product limit methods and compared across groups using log rank statistic. Cox proportional hazards models were used to determine the association of survival outcomes and annexin expression (continuous variable) adjusted by patient and tumor characteristics. Results: Median age at diagnosis was 62 years. 41 (9.6%), 245 (57.5%), 25 (5.9) and 115 (27.0%) patients had Her2 positive, hormone receptor (HR) positive, metaplastic and triple negative (TNBC) disease respectively. For the whole cohort 44 (10%), 235 (55.2%), 119 (27.9%), 28 (6.6%) breast tumors were classified as having negative, low, medium and high annexin expression respectively. High annexin A1 levels were associated with hormone receptor positive disease, increased age, post-menopausal status, low grade and lower disease stage. Median annexin A1 level was −0.19, 0.0, −0.34, −0.2 among tumors that were HER2 positive, HR positive, metaplastic and TNBC disease respectively. 5-yearRFS was 65.8% and 84.9% respectively among women with negative/low and medium/high annexin A1 levels respectively (p < 0.0001). Among women with Her2 positive, HR positive, metaplastic or TNBC disease 5-year RFS was significantly higher among tumors with medium/high annexin A1 levels. In the multivariable model an increase in annexin was associated with a 13% reduction in the risk of recurrence (HR = 0.87, 95% CI 0.60–1.26, p = 0.46). Conclusion: In this large dataset with long follow up our results indicate that high annexin A1 expression among women with breast cancer was associated with favorable patient and tumor characteristics and an improved RFS. Annexin A1 should be explored further as a potential prognostic biomarker. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-07-25.