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This study investigated the prognostic impact of WES-defined\n                      <jats:italic>ERBB2<\/jats:italic>\n                      amplification and its association with adjuvant chemotherapy (ACT) efficacy and circulating tumor DNA (ctDNA) in resectable CRC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Data from 3607 patients with resectable CRC from the GALAXY study were analyzed.\n                      <jats:italic>HER2<\/jats:italic>\n                      amplification was defined using\n                      <jats:italic>ERBB2<\/jats:italic>\n                      copy number alterations based on whole exome sequencing of tumor specimens. We analyzed disease-free survival (DFS) in WES-defined\n                      <jats:italic>ERBB2<\/jats:italic>\n                      amplified CRC, evaluating ACT benefit and the correlation between\n                      <jats:italic>ERBB2<\/jats:italic>\n                      copy number and ctDNA status.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      No significant difference in DFS was observed between those with and without WES-defined\n                      <jats:italic>ERBB2<\/jats:italic>\n                      amplification in a univariate (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.0659) or a multivariate analysis (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.2300). Among patients with pathological stage III, ACT was associated with improved DFS in the non-amplified subgroup (HR 0.67,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.0002), particularly in the subgroup of patients with early post-operative (2\u201310 weeks following surgical resection) ctDNA-positivity (HR 0.27,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.0001), whereas no clear association was detected in the small amplified subgroup; however, the ACT-by-\n                      <jats:italic>ERBB2<\/jats:italic>\n                      amplification interaction was not statistically significant. While WES-defined\n                      <jats:italic>ERBB2<\/jats:italic>\n                      amplification correlated with higher early post-operative ctDNA positivity (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.0486),\n                      <jats:italic>ERBB2<\/jats:italic>\n                      copy number did not associate with recurrence or levels. However, early post-operative ctDNA positivity strongly predicted poor DFS in patients with WES-defined\n                      <jats:italic>ERBB2<\/jats:italic>\n                      amplification (HR 15.26,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.0001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      WES-defined\n                      <jats:italic>ERBB2<\/jats:italic>\n                      amplification was not identified as a significant adverse prognostic factor in resectable CRC, unlike early post-operative ctDNA status. The limited number of amplified cases precluded a reliable assessment of whether WES-defined\n                      <jats:italic>ERBB2<\/jats:italic>\n                      amplification modifies the association between ACT and DFS.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10147-026-03161-5","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T11:28:09Z","timestamp":1787225289000},"page":"2512-2523","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical significance of WES-defined ERBB2 amplification in resectable colorectal 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