Breast Cancer Index and Prediction of Extended Aromatase Inhibitor Therapy Benefit in Hormone Receptor-positive Breast Cancer from the NRG Oncology/NSABP B-42 Trial.

PURPOSE:BCI (H/I) has been shown to predict extended endocrine therapy (EET) benefit. We examined BCI (H/I) for EET benefit prediction in NSABP B-42, which evaluated extended letrozole therapy (ELT) in hormone receptor-positive breast cancer patients after 5 years of ET. METHODS:Stratified Cox model was used to analyze RFI as primary endpoint, with DR, BCFI, and DFS, as secondary endpoints. Due to a non-proportional effect of ELT on DR, time-dependent analyses were performed. RESULTS:The translational cohort included 2,178 patients (45% BCI (H/I)-High, 55% BCI (H/I)-Low). ELT showed an absolute 10-year RFI benefit of 1.6% (P=0.10), resulting in an underpowered primary analysis (50% power). ELT benefit and BCI (H/I) did not show a significant interaction for RFI (BCI [(H/I])-Low: 10y absolute benefit 1.1% [HR=0.70, 0.43-1.12, P=0.13]; BCI [(H/I])-High: 2.4% [HR=0.83, 0.55-1.26, p=0.38]; Pinteraction=0.56). Time-dependent DR analysis showed that after 4y, BCI (H/I)-High patients had significant ELT benefit (HR=0.29, 0.12-0.69, P<0.01), whereas BCI (H/I)-Low patients were less likely to benefit (HR=0.68, 0.33-1.39, P=0.29) (Pinteraction=0.14). Prediction of ELT benefit by BCI (H/I) was more apparent in the HER2- subset after 4y (ELT-by-BCI (H/I) Pinteraction=0.04). CONCLUSIONS:BCI(H/I)-High vs -Low did not show a statistically significant difference in ELT benefit for the primary endpoint (RFI). However, in time-dependent DR analysis, BCI (H/I)-High patients experienced statistically significant benefit from ELT after 4y, whereas (H/I)-Low patients did not. Because BCI (H/I) has been validated as a predictive marker of EET benefit in other trials, additional follow-up may enable further characterization of BCI's predictive ability.