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Background: Insulin receptor substrate 1 (IRS-1) has been known to be an associated factor with breast cancer progression. However, there has been little study with respect to the relationship between the expression of IRS-1 and breast cancer prognosis in clinical practice. In this study, we evaluated the impact of the estrogen receptor (ER) and IRS-1 on the recurrence and survival of breast cancer patients.Methods: We analyzed the pathologic finding of 376 tissue samples from breast cancer patients who received proper treatment between January 1990 and December 2006 using the tissue microarray. We measured the expression of ER and IRS-1 by immunohistochemistry staining and analyzed the difference of recurrence and survival rate in each subgroup of ER and IRS-1.Results: Our results show that there is a significant difference of disease-free survival (DFS) according to ER and IRS-1 subgroups with both univariate and multivariate analyses. Specifically, ER-positive and IRS-1-positive breast cancer samples showed improved DFS compared to ER-positive and IRS-1-negative breast cancer (adjusted hazard ratio: 2.17; 95% confidence interval: 1.15-4.09; P = 0.01). There was a difference of overall survival according to ER and IRS-1 subgroups by univariate analysis (P = 0.01), but not by multivariate analysis (P = 0.36).Conclusion: ER and IRS-1 subgroups appear to be critical factors for the prediction of breast cancer recurrence. In particular, we suggest that the patients who have ER-positive and IRS-1-negative breast cancer undergo more aggressive treatment because they have poorer prognoses. [ABSTRACT FROM AUTHOR]