Data from Breast Cancer Index Is a Predictive Biomarker of Treatment Benefit and Outcome from Extended Tamoxifen Therapy: Final Analysis of the Trans-aTTom Study

Abstract

<div>AbstractPurpose:<p>The Breast Cancer Index (BCI) <i>HOXB13/IL17BR</i> (H/I) ratio predicts benefit from extended endocrine therapy in hormone receptor–positive (HR⁺) early-stage breast cancer. Here, we report the final analysis of the Trans-aTTom study examining BCI (H/I)'s predictive performance.</p>Experimental Design:<p>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.</p>Results:<p>Final analysis of the overall study population (<i>N</i> = 2,445) did not show a significant improvement in RFI with extended tamoxifen [HR, 0.90; 95% confidence interval (CI), 0.69–1.16; <i>P</i> = 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⁺ subset (<i>N</i> = 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; <i>P</i> = 0.016), whereas BCI (H/I)-Low patients did not (−1.2% absolute benefit; HR, 1.11; 95% CI, 0.76–1.64; <i>P</i> = 0.581). A significant treatment-to-biomarker interaction was demonstrated on the basis of RFI, DFI, and DFS (<i>P</i> = 0.037, 0.040, and 0.025, respectively). BCI (H/I)-High patients remained predictive of benefit from extended tamoxifen in the N⁺/HER2⁻ subgroup (9.4% absolute benefit: HR, 0.35; 95% CI, 0.15–0.81; <i>P</i> = 0.047). A three-way interaction evaluating BCI (H/I), treatment, and HER2 status was not statistically significant (<i>P</i> = 0.849).</p>Conclusions:<p>Novel findings demonstrate that BCI (H/I) significantly predicts benefit from extended tamoxifen in HR⁺ N⁺ patients with HER2⁻ disease. Moreover, BCI (H/I) demonstrates significant treatment to biomarker interaction across survival outcomes.</p></div>