Breast Cancer Index is a predictive biomarker of treatment benefit and outcome from extended tamoxifen therapy: final analysis of the Trans-aTTom study

Purpose: The Breast Cancer Index (BCI) HOXB13/IL17BR (H/I) ratio predicts benefit from extended endocrine therapy in hormone receptor–positive (HR ^þ) early-stage breast cancer. Here, we report the final analysis of the Trans-aTTom study examining BCI (H/I)’s predictive performance. Experimental Design: BCI results were available for 2,445 aTTom trial patients. The primary endpoint of recurrence-free interval (RFI) and secondary endpoints of disease-free interval (DFI) and disease-free survival (DFS) were examined using Cox proportional hazards regression and log-rank test. Results: Final analysis of the overall study population (N ¼ 2,445) did not show a significant improvement in RFI with extended tamoxifen [HR, 0.90; 95% confidence interval (CI), 0.69–1.16; P ¼ 0.401]. Both the overall study population and N0 group were underpowered due to the low event rate in the N0 group. In a pre-planned analysis of the N ^þ subset (N ¼ 789), BCI (H/I)-High patients derived significant benefit from extended tamoxifen (9.7% absolute benefit: HR, 0.33; 95% CI, 0.14–0.75; P ¼ 0.016), whereas BCI (H/I)-Low patients did not (-1.2% absolute benefit; HR, 1.11; 95% CI, 0.76–1.64; P ¼ 0.581). A significant treatment-to-biomarker interaction was demonstrated on the basis of RFI, DFI, and DFS (P ¼ 0.037, 0.040, and 0.025, respectively). BCI (H/I)-High patients remained predictive of benefit from extended tamoxifen in the N ^þ/HER2 ^- subgroup (9.4% absolute benefit: HR, 0.35; 95% CI, 0.15–0.81; P ¼ 0.047). A three-way interaction evaluating BCI (H/I), treatment, and HER2 status was not statistically significant (P ¼ 0.849). Conclusions: Novel findings demonstrate that BCI (H/I) significantly predicts benefit from extended tamoxifen in HR ^þ N ^þ patients with HER2 ^- disease. Moreover, BCI (H/I) demonstrates significant treatment to biomarker interaction across survival outcomes.