Evidence of PIK3CA and TP53 co-mutation in breast cancer identification on next-generation sequencing (NGS) of ERBB2 (HER2)-amplified residual disease following preoperative anti-HER2 therapy.

Abstract

625 Background: Understanding the molecular alterations in residual, treatment-refractory HER2-positive breast cancer (BC) following preoperative trastuzumab (H), lapatinib (L) or both (HL) in combination with chemotherapy may help identify patients at risk for not achieving pathologic complete responses as well as genomic alterations (GA) to target to overcome therapy resistance. Here we summarize the GA present in 21 pts’ residual BC following preoperative anti-HER2 therapy. Methods: 100 pts with stage 2/3 HER2+ BC were randomized to treatment with H vs L 1250mg vs HL (L 750-1000mg) along with preoperative 5-fluoruracil, epirubicin, cyclophosphamide followed by weekly paclitaxel (Holmes F. BMC Res Notes 6:507, 2013). Following IRB-approved informed consent, targeted NGS was performed on 21 pts’ FFPE residual disease (RD) after preoperative therapy at a CLIA-certified laboratory to characterize all classes of genomic alterations across 287 cancer-related genes. Results: 3 of 21 pts with RD were HER2-nega...