For a Trans-bottom study, researchers sought to analyze the predictive performance of BCI (H/I). BCI results for 2,445 aTTom trial patients were available. Cox proportional hazards regression and the log-rank test were used to examine the primary endpoint of recurrence-free interval (RFI) and secondary endpoints of disease-free interval (DFI) and disease-free survival (DFS). Final analysis of the entire study population (N=2,445) revealed no significant improvement in RFI with extended tamoxifen [HR, 0.90; 95% CI, 0.69–1.16; P=0.401]. Because of the low event rate in the N0 group, both the overall study population and the N0 group were underpowered. In a planned analysis of the N+ subset (N=789), BCI (H/I)-High patients benefited from extended tamoxifen (9.7% absolute benefit: HR, 0.33; 95% CI, 0.14–0.75; P=0.016), but BCI (H/I)-Low patients did not (−1.2% absolute benefit; HR, 1.11; 95% CI, 0.76–1.64; P=0.581). RFI, DFI, and DFS showed a significant treatment-to-biomarker interaction (P=0.037, 0.040, and 0.025, respectively). In the N+/HER2 subgroup, BCI (H/I)-High patients remained predictive of benefit from extended tamoxifen (9.4% absolute benefit: HR, 0.35; 95% CI, 0.15–0.81; P=0.047). The interaction of BCI (H/I), treatment, and HER2 status was not statistically significant (P=0.849). According to new research, BCI (H/I) significantly predicts benefits from extended tamoxifen in HR+ N+  patients with HER2 disease. Furthermore, BCI (H/I) showed significant treatment-biomarker interaction across all survival outcomes.