e11057 Background: Controversy has developed over the use of hormone replacement therapy (HRT) and its association with the future risk of breast cancer. The biology of breast cancer diagnosed after the use of HRT is different than in non HRT users. One such pathologic feature that may be affected by the use of HRT is HER2 neu. While there is existing data illustrating the relationship between HRT and breast cancer, there is little data examining the relationship between HRT and HER2 neu. The purpose of this study is to investigate that relationship and determine whether or not the use of HRT has any effect on the HER2 neu status of primary breast cancers. Methods: A retrospective review of a prospective database identified 2,928 patients with primary breast cancer with a history of prior/current HRT use. Tumor specimens were evaluated for HER2 neu expression at the time of surgery using either IHC or FISH. Pearson’s χ² test along with evaluation of odds ratios were used to determine whether or not there was an association of HER2 neu expression with HRT use. Results: Table 1A illustrates the lack of a correlation between increasing HER2 expression and HRT. There was no significant change in odds of HRT use as HER2 expression increased. After confirming HER2 neu status using FISH, the odds of HER2 positivity among HRT users was OR= 1.05 times the odds of HER2 neu positivity among non-HRT users [C.I. 0.85, 1.29; p = 0.63] (Table 1B). Conclusions: Contrary to our expectation of an inverse relationship between HRT use and HER2 negative phenotype, we found no clear association between the two. Limitations of this study include the inability to discriminate from our data set between current and prior users, and between estrogen alone and combination estrogen/progesterone supplementation. Additionally, the definition of HER2 positivity by membranous staining has changed over the last decade, which may be contributory. We plan on determining the relationship between HER2 status and ER status as it relates to HRT use in future studies. [Table: see text] [Table: see text]