Breast Cancer Index (BCI) and prediction of benefit from extended aromatase inhibitor (AI) therapy (tx) in HR+ breast cancer: NRG oncology/NSABP B-42

501 Background: The BCI HOXB13/IL17BR ratio (BCI-H/I) has been shown to predict endocrine tx (ET) and extended ET (EET) benefit. We examined the effect of BCI-H/I for EET benefit prediction in NSABP B-42, evaluating extended letrozole tx (ELT) in HR+ breast cancer patients (pts) who completed 5 yrs of ET. Methods: All pts with available primary tumor tissue were eligible. Primary endpoint was recurrence-free interval (RFI). Secondary endpoints were distant recurrence (DR), breast cancer-free interval (BCFI), and disease-free survival (DFS). Stratified Cox proportional hazards model was used. Due to a non-proportional effect of ELT on DR, time-dependent secondary analyses (≤4y, >4y) were performed. Likelihood ratio test evaluated treatment by BCI-H/I interaction. Results: In 2,179 pts analyzed (60% N0; 62% AI only; 80% HER2-), 45% were BCI-H/I-High and 55% BCI-H/I-Low. ELT showed an absolute 10y benefit of 1.6% for RFI (HR=0.77, 95% CI 0.57-1.05, p=0.10) (BCI-H/I-Low: 1.1% [HR=0.69, 0.43-1.11, p=0.13]; BCI-H/I-High: 2.4% [HR=0.83, 0.55-1.26, p=0.38]; interaction p=0.55). There was no statistically significant ELT by BCI-H/I interaction for BCFI (BCI-H/I-Low: HR=0.53, 0.36-0.78, p=0.001; BCI-H/I-High: HR=0.85, 0.60-1.21, p=0.36; interaction p=0.07) or for DFS (BCI-H/I-Low: HR=0.75, 0.58-0.95, p=0.017; BCI-H/I-High: HR=0.81, 0.64-1.04, p=0.09; interaction p=0.62). Before 4y, there was no statistically significant ELT benefit on DR in either BCI-H/I group. After 4y, BCI-H/I-High pts had statistically significant ELT benefit on DR (HR: 0.29, 0.12-0.69, p=0.003), while BCI-H/I-Low pts were less likely to benefit (HR: 0.68, 0.33-1.39, p=0.28) (interaction p=0.14). Conclusions: BCI-H/I prediction of ELT benefit on RFI was not confirmed. In time-dependent DR analyses, BCI-H/I-High pts had statistically significant benefit from ELT after 4y, while BCI-H/I-Low pts did not. Observed ELT benefit on BCFI in BCI-H/I-Low pts was primarily driven by second primary breast cancers. Additional follow-up is needed to further characterize BCI-H/I predictive ability in this study. Support: U10CA180868, -180822, U24CA196067; Novartis; Biotheranostics. Clinical trial information: NCT00382070. [Table: see text]