Background: BCI is a validated gene expression-based assay that stratifies patients based on risk of overall (0-10y) and late (post-5y) distant recurrence (DR) and predicts likelihood of benefit from extended endocrine therapy (EET). The Trans-aTTom study established Level1B validation for BCI (H/I) to predict benefit from EET.¹ In this updated Trans-aTTom analysis including HER2 status, BCI (H/I) and prediction of endocrine benefit were further characterized. Methods: Centralized HER2 was determined for all cases according to current ASCO/CAP guidelines. Kaplan-Meier and Cox proportional hazards regression were conducted to assess primary and secondary endpoints of Recurrence-Free Interval (RFI) and Disease-Free Interval (DFI), respectively. A three-way interaction using likelihood ratio testing, which included treatment, BCI (H/I) and HER2, was performed to assess the effect of HER2 on BCI (H/I) prediction of EET benefit. Results: Of 789 N+ patients, 90% (N = 711) and 9% (N = 72) were HR+/HER2- and HR+/HER2+, respectively. In the HER2- subset, BCI (H/I)-High (48%) showed significant benefit from 10y vs. 5y of tamoxifen (9.4% RFI: HR = 0.35 [95% CI 0.15-0.81]; P = 0.047) while BCI (H/I)-Low patients did not (-2.1% RFI; HR = 1.15 [95% CI 0.78-1.69]; P = 0.491). For DFI, BCI (H/I)-High patients also showed significant benefit (10.3% DFI; HR = 0.41 [95% CI 0.18-0.91]; P = 0.047) while BCI (H/I)-Low patients did not (-1.7% DFI; HR = 1.10 [95% CI 0.75-1.62] P = 0.612). As demonstrated in the overall N+ cohort, significant interaction between BCI (H/I) and treatment was shown in the HER2- subset (RFI P = 0.045; DFI P = 0.044). Notably, three-way interaction evaluating BCI (H/I), treatment and HER2 status was not statistically significant (P = 0.85), indicating the ability of BCI (H/I) to predict benefit of EET activity was not significantly affected by HER2 status. Conclusions: In this updated Trans-aTTom analysis with HER2 data, BCI (H/I) showed similar predictive performance for EET response in the HER2- subset when compared to the overall N+ cohort. These data further support the clinical utility of BCI (H/I) as a predictive biomarker for informing EET benefit in HR+/HER2- and HR+/HER2+ disease. Clinical trial information: NCT00003678.

¹Bartlett JMS et al, Annal Oncol. 2019.