Molecular alterations and late recurrence in postmenopausal women with hormone receptor-positive node-positive breast cancer (BC): Results from the “SOLE” trial.

517Background: Women with hormone receptor-positive BC have an ongoing risk of relapse. We performed molecular analyses of primary BC from postmenopausal patients (pts) enrolled in the extended adjuvant intermittent letrozole vs. continuous letrozole (SOLE) trial to identify prognostic factors and potential targets. Methods: From 4884 pts enrolled, 3162 had FFPE tumor samples and were eligible. A case-cohort design selected 599 pts, and 499 DNA samples underwent next-generation sequencing of 35 and 19 actionable genes for mutation (SNV) and copy number gain (CNG) analyses. Correlations of SNV/CNG with clinicopathologic factors were analyzed. Associations with breast cancer free-interval (BCFI) and distant recurrence free-interval (DRFI) were assessed using weighted proportional hazards models to obtain unbiased and consistent estimates representing the overall trial population. With 403 pts there was 90% power to detect a hazard ratio (HR) = 2.0 (SNV/CNG+ vs. -; assuming a 40% mutation prevalence), with 0...