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Whole exome sequencing of long-term, never relapse exceptional responders of trastuzumab-treated HER2+ metastatic breast cancer

ABSTRACT: Trastuzumab has significantly improved the overall survival of patients with HER2+ metastatic breast cancer (MBC). However, outcomes can vary, with patients progressing within 1-year of treatment or exceptional cases of complete response to trastuzumab for Ã¢Â‰Â¥ 10 years. Identification of the underlying genomic aberrations of Ã¢Â€Âœexceptional responders (ExRs)Ã¢Â€Â compared to Ã¢Â€Âœrapid non-responders (NR)Ã¢Â€Â increases our understanding of the mechanisms involved in MBC progression and identification of biomarkers of trastuzumab response and resistance. Whole exome sequencing was performed on six ExRs compared to five NR. The overall fraction of genome copy number alteration (CNA) burden was higher in NR patients (P=0.07), while more significantly pronounced in copy number gains (P=0.03) in NR compared to ExRs. Delineation of the distribution of CNA burden across the genome identified a greater degree of CNA burden in NR within chr8 (P=0.02) and in chr17 (P=0.06) and conferred a statistically significant benefit in overall survival.

PROVIDER: EGAS00001004486 | EGA |

REPOSITORIES: EGA

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