Background: The recent Trial Assigning Individualized Options for Treatment (TAILORx) was practice changing. However, several important questions remain unanswered about therapy for women with early stage, hormone receptor positive (HR+), HER2- breast cancers, including chemotherapy effects by age and different Oncotype recurrence score (RS) cut-points, and longer follow-up. We developed a simulation model to extend the trial results to begin to fill these gaps. Methods: We developed a simulation model using an empirical Bayesian approach to simulate women eligible for the TAILORx trial. The joint distributions of patient and tumor characteristics were derived from de-identified TAILORx data. The remaining inputs used data independent of the trial, including SEER, the Oxford Overview, and other trials. TAILORx was simulated to examine the effects of chemotherapy (+ hormonal Rx) vs. hormonal Rx alone on distant recurrence-free survival (DRFS) at 9- and 20-years by age (≤50 and >50 years) and RS (11-25 and 16-25). We also evaluated the effects of chemotherapy in women with RS 26-30. Hazard ratios (HR) were determined using Cox regressions and DRFS by treatment were derived from Kaplan-Meier curves. We report the mean results from 1000 trial simulations, where each simulation randomly sampled values for each parameter from their observed joint distribution. Finally, the original trial was replicated for model validation. Results: The model closely replicated actual trial results. Sample sizes ranged from 7000-10000. The model estimated that chemotherapy improved DFRS in women aged ≤50 with RS 16-25 (Table). The 20-year event rates remained low in the 11-25 category. Among women with RS 26-30, HR for no chemo vs. chemo was 1.38 (95% CI:1.18-1.58). Conclusions: Simulation suggests that chemotherapy may reduce distant recurrence in younger women at different cut points between 11-25. Simulation modeling may be useful to translate trial results to broader population subgroups than those possible to test in RCTs. Nine-year distant recurrence-free survival by chemotherapy.

* No Chemo vs. Chemo