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

Breast Cancer - HER2/ER
Session Type and Session Title: 
Clinical Science Symposium, Harnessing Biology and Immunology to Develop Novel Biomarkers
Abstract Number: 
J Clin Oncol 32:5s, 2014 (suppl; abstr 509)
Edith A. Perez, E. Aubrey Thompson, S. Keith Anderson, Yan W. Asmann, Krishna R. Kalari, Jeanette Eckel-Passow, Amylou C. Dueck, Kathleen S. Tenner, Jin Jen, Jian-Bing Fan, Xochiquetzal Geiger, Ann E. McCullough, Beiyun Chen, Michael Zschunke, Robert B. Jenkins, George W. Sledge, Eric P. Winer, Julie Gralow, Monica Madden Reinholz, Karla V. Ballman; Mayo Clinic, Jacksonville, FL; Mayo Clinic, Rochester, MN; Mayo Clinic, Scottsdale, AZ; Illumina, Inc., San Diego, CA; Stanford University, Palo Alto, CA; Dana-Farber Cancer Institute, Boston, MA; Seattle Cancer Care Alliance, Seattle, WA

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures


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 p<0.01, 10/13 significantly enriched biological processes associated with increased RFS (p<0.01) were linked to immune functions. These 10 processes defined a cohort of 87 immune function genes. Patients defined as immune function positive based on the 87 genes experienced a favorable outcome when treated with H (HR=0.55, p=0.0005). Patients who did not exhibit immune function enrichment and were treated with H did not have better RFS than patients with immune function enrichment who were treated with chemotherapy alone (HR=0.93, p=0.72). Among patients who received chemotherapy alone, enriched immune function was not associated with increased RFS (HR=1.01, p=0.96). Conclusions: Improved RFS following treatment with adjuvant H appears to be associated with a heightened state of immunological function. This observation may define a significant biological process that is linked to the efficacy of HER2-targeted therapy, may provide a means of predicting probability of relapse following adjuvant trastuzumab, and suggests possible routes of therapeutic enhancement.