Abstract: Objective To investigate the expression of HER4 in invasive breast cancer and its correlation with clinical characteristics and the prognosis.Methods Out of 58 patients with primary invasive breast carcinoma,32 underwent recurrence within 5 years and 26 did not.The expression of ER,HER2 and HER4 was detected by immunohistochemistry.The overall survival and relapse-free survival were followed up.Results The positive expression of ER,HER2 or HER4 was 31/58(53.4%),14/58(24.1%)and 19/58(32.8%),respectively.Non-recurrence group had a higher expression of HER4(P=0.05)and lower expression of HER2(P=0.043),but presented similar level of ER to that in recurrence group(P=0.866).Univariate analysis showed positive expression of HER4 had a significant relapse-free survival advantage(P=0.023)and a tendency of longer overall survival(P=0.057).However,HER2 manifested a negative effect on both relapse-free survival(P=0.048)and overall survival(P=0.02).In addition,coexpression status of HER2 and HER4 was aslo correlated with the relapse-free survival(P=0.016)and overall survival(P=0.014),with the best outcome in HER2-/HER4+ group.In multivariate analysis,more involved axillary lymphnodes,positive expression of HER2 and lack of HER4 expression were independently associated with a poor overall survival.The number of positive axillary lymphnodes and HER4 status were influencing factors for relapse-free survival as well.Conclusion HER4 status was an independent prognostic factor for invasive breast cancer and its positive expression predicts better outcome.