Copy Number Aberration Analysis to Predict Response to Neoadjuvant Anti-HER2 Therapy: Results from the NeoALTTO Phase III Clinical Trial

PURPOSE: The heterogeneity of response to anti-HER2 agents represents a major challenge in patients with HER2-positive breast cancer. To better understand the sensitivity and resistance to trastuzumab and lapatinib, we investigated the role of copy number aberrations (CNA) in predicting pathologic complete response (pCR) and survival outcomes in the NeoALTTO trial. EXPERIMENTAL DESIGN: The neoadjuvant phase III NeoALTTO trial enrolled 455 patients with HER2-positive early-stage breast cancer. DNA samples from 269 patients were assessed for genome-wide copy number profiling. Recurrent CNAs were found with GISTIC2.0. RESULTS: WT subgroup. Interestingly, a gene-ontology analysis highlighted several immune processes correlated to 6q23-24 copy number. CONCLUSIONS: amplification. The complexity of the 6q23-24 region warrants further investigation.