Association of genomic analysis of immune function genes and clinical outcome in the NCCTG (Alliance) N9831 adjuvant trastuzumab trial.

509 Background: Some 20-25% of patients with HER2+ disease relapse after adjuvant trastuzumab (H). We used a genomic approach to define biological processes that predict benefit from H. Methods: Whole genome DASL technology was used to identify genes associated with relapse-free survival (RFS) among 1,282 patients enrolled in the N9831 adjuvant H trial (NCT00005970). Cox proportional hazard ratios (HR), adjusted for significant clinical/pathological risk factors, were used to determine the association of each gene with RFS (median follow-up 6years, 11months) for 433 patients who received chemotherapy alone and 849 patients who received chemotherapy plus H. Functional ontology analysis and network modeling were used to identify key biological processes associated with RFS in patients who received chemotherapy alone or chemotherapy plus trastuzumab. Results: Using probes with HR pu003c0.01, 10/13 significantly enriched biological processes associated with increased RFS (pu003c0.01) were linked to immune functions. ...