In the present study, ER+/HER2+ patients treated with trastuzumab had significantly better 5-year DFS (HR 0.52, 95% CI: 0.37–0.73, P <  0.001) and OS (HR 0.38, 95% CI: 0.22–0.67, P = 0.037) rates than those with ER+/HER2- tumor in multivariable analysis by adjusting clinicopathological factors, indicating HER2 positivity was no longer an adverse factor for ER+ patients if they were treated with trastuzumab, which may guide further clinical treatment decision making. The gene discussed is ESR1; the disease is neoplasm.