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Background: The natural course of traditionally prognostically unfavorable human epidermal growth factor receptor 2 (HER2)-positive breast cancer has been changed by anti-HER2 therapy. It is not clear whether the prognosis for HER2-positive patients treated with adjuvant trastuzumab differs from that of HER2-negative patients., Methods: We performed a retrospective study including patients with lymph node-negative invasive breast cancer treated at our institution in the period 2000-2009. Disease-free (DFS) and overall survival (OS) were calculated using the Kaplan-Meier method. The Cox proportional hazards model was applied to control for other clinically important variables., Results: Median follow-up was 90-109 months. The 5-year DFS rates for HER2-negative patients, HER2-positive patients without adjuvant trastuzumab and trastuzumab-treated HER2-positive patients were 88.1% (95% confidence interval (CI) 85.6-90.6%), 73.1% (95% CI 64.3-81.9%) and 90.7% (95% CI 83.1-98.3%), respectively. No significant difference in DFS was observed between trastuzumab-treated HER2-positive patients and HER2-negative patients in multivariate analysis (hazard ratio 1.15; 95% CI 0.53-2.46; p = 0.728). There were no differences in OS among the 3 groups., Conclusion: Based on our results, the negative prognostic effect of HER2 positivity seen before targeted anti-HER2 treatment has completely disappeared in the era of routine trastuzumab administration in the adjuvant setting.