{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T02:09:50Z","timestamp":1777860590206,"version":"3.51.4"},"reference-count":33,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Oncotype DX has played a critical role in guiding treatment decisions for hormone receptor (HR)\u2013positive, HER2\u2010negative early\u2010stage breast cancer. Clinically, a subset of patients with low Oncotype recurrent score (RS) will still progress on standard therapy and ultimately develop metastasis. Our goal was to explore potential molecular mechanisms, including specific genetic alterations and pathway activity associated with disease progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We retrospectively reviewed a small series of low RS breast cancers with subsequent metastasis and analysed the clinicopathological characteristics and comprehensive genomic profiling (CGP) data from tumour tissue and circulating tumour DNA (ctDNA) by liquid biopsy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      These tumours demonstrated a range of histopathologic features and molecular profiles. Common findings included enrichment of\n                      <jats:italic>PIK3CA<\/jats:italic>\n                      and\n                      <jats:italic>TP53<\/jats:italic>\n                      mutations and treatment\u2010emergent\n                      <jats:italic>ESR1<\/jats:italic>\n                      mutations, observed in both tissue and ctDNA.\n                      <jats:italic>CDKN2A<\/jats:italic>\n                      ,\n                      <jats:italic>SPEN<\/jats:italic>\n                      ,\n                      <jats:italic>KIT<\/jats:italic>\n                      ,\n                      <jats:italic>CTNNB1<\/jats:italic>\n                      ,\n                      <jats:italic>MYC<\/jats:italic>\n                      ,\n                      <jats:italic>EMSY<\/jats:italic>\n                      ,\n                      <jats:italic>KMT2C<\/jats:italic>\n                      ,\n                      <jats:italic>MAP3K1<\/jats:italic>\n                      gene alterations were only found in low RS group in low frequency. Copy number amplifications events were less common in low RS group. In cases with both tissue and ctDNA data, tissue CGP proved useful baseline for identifying driver mutations such as\n                      <jats:italic>PIK3CA<\/jats:italic>\n                      and for contextualizing ctDNA findings, and ctDNA analysis was adequate for disease monitoring and tracking molecular evolution over time.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Using real\u2010world CGP of tumour tissue and ctDNA, we identified key molecular features associated with endocrine resistance in patients with low RS who later developed metastases.\n                      <jats:italic>PIK3CA<\/jats:italic>\n                      mutation and other ER group\u2010related mutations contributed to the low RS. Tissue CGP provides baseline for interpreting ctDNA, and ctDNA monitoring\n                      <jats:italic>PIK3CA, TP53<\/jats:italic>\n                      ,\n                      <jats:italic>ESR1<\/jats:italic>\n                      and other pathogenic or driver mutations in the early course of low RS cases may represent an excellent non\u2010invasive option for identifying targets and early intervention to prevent disease progression, though a large validation study is needed.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/his.70115","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T08:44:07Z","timestamp":1770713047000},"page":"1451-1458","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genomic and clinicopathological characteristics of low\u00a0oncotype recurrent score breast cancers with subsequent metastasis"],"prefix":"10.1111","volume":"88","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5329-4666","authenticated-orcid":false,"given":"Liu","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Rhode Island Hospital Warren Alpert Medical School of Brown University  Providence RI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1928-1722","authenticated-orcid":false,"given":"Stephanie L.","family":"Graff","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Rhode Island Hospital Warren Alpert Medical School of Brown University  Providence RI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6061-0781","authenticated-orcid":false,"given":"Sean","family":"Hacking","sequence":"additional","affiliation":[{"name":"Department of Pathology, NYU Langone Health NYU Grossman School of Medicine  New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6049-5293","authenticated-orcid":false,"given":"Liang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Rhode Island Hospital Warren Alpert Medical School of Brown University  Providence RI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1252-5579","authenticated-orcid":false,"given":"Yihong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Rhode Island Hospital Warren Alpert Medical School of Brown University  Providence RI 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