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 ≥10 years. Identification of the underlying genomic aberrations of "exceptional responders (ExRs)" compared to "rapid non-responders (NRs)" 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. Clinical trial number: NCT01722890 [ICORG 12/09].

journal_name

Br J Cancer

authors

Walsh N,Andrieu C,O'Donovan P,Quinn C,Maguire A,Furney SJ,Gullo G,Crown J

doi

10.1038/s41416-020-0999-z

subject

Has Abstract

pub_date

2020-10-01 00:00:00

pages

1219-1222

issue

8

eissn

0007-0920

issn

1532-1827

pii

10.1038/s41416-020-0999-z

journal_volume

123

pub_type

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