{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T14:37:38Z","timestamp":1786113458538,"version":"build-2736575974"},"reference-count":49,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100001831","name":"Lynn Sage Breast Cancer Foundation","doi-asserted-by":"publisher","award":["OncoSET Precision Medicine Program\/ National Insti"],"award-info":[{"award-number":["OncoSET Precision Medicine Program\/ National Insti"]}],"id":[{"id":"10.13039\/100001831","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:p>\n                    Endocrine resistance is a complex phenomenon, including alterations of the\n                    <jats:italic>ESR1<\/jats:italic>\n                    gene. The aim of this study was to simultaneously analyze\n                    <jats:italic>ESR1<\/jats:italic>\n                    promoter methylation and\n                    <jats:italic>ESR1<\/jats:italic>\n                    hotspot mutations in circulating tumor cells (CTCs) and paired plasma\u2010circulating tumor DNA (ctDNA) from patients with estrogen receptor\u2010positive (ER+) advanced breast cancer (BC). We retrospectively analyzed samples from 42 ER+ advanced BC patients characterized for CTCs and ctDNA at Northwestern University. CTCs were enumerated using the CellSearch\u00ae system, while ctDNA was analyzed with the Guardant360 NGS platform. Genomic DNA from CellSearch\u2010enriched CTC fractions was amplified and analyzed using the ESR1\u2010NAPA assay.\n                    <jats:italic>ESR1<\/jats:italic>\n                    methylation analysis was performed in 34 samples.\n                    <jats:italic>ESR1<\/jats:italic>\n                    mutations were detected in 59.5% CTC\u2010derived samples, a significantly higher proportion than in paired plasma ctDNA (29.6%).\n                    <jats:italic>ESR1<\/jats:italic>\n                    methylation was observed in 26.5% patients. Concurrent\n                    <jats:italic>ESR1<\/jats:italic>\n                    mutations and methylation were identified in six cases, suggesting combined genetic and epigenetic mechanisms of endocrine resistance. Overall, CTC\u2010derived genomic DNA showed higher sensitivity for detecting\n                    <jats:italic>ESR1<\/jats:italic>\n                    mutations than plasma ctDNA, supporting the potential value of CTC analysis for characterizing endocrine resistance in advanced BC.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.70254","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T17:39:54Z","timestamp":1779903594000},"page":"2102-2113","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>\n                      <i>ESR1<\/i>\n                    <\/scp>\n                    methylation and\n                    <scp>\n                      <i>ESR1<\/i>\n                    <\/scp>\n                    mutations in circulating tumor cells (\n                    <scp>CTCs<\/scp>\n                    ) and paired plasma\u2010\n                    <scp>cfDNA<\/scp>\n                    of advanced breast cancer patients: A feasibility proof\u2010of\u2010concept study"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3492-491X","authenticated-orcid":false,"given":"Dimitra","family":"Stergiopoulou","sequence":"first","affiliation":[{"name":"Analysis of Circulating Tumor Cells, Laboratory of Analytical Chemistry, Department of Chemistry University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7760-9701","authenticated-orcid":false,"given":"Athina","family":"Markou","sequence":"additional","affiliation":[{"name":"Analysis of Circulating Tumor Cells, Laboratory of Analytical Chemistry, Department of Chemistry University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Nicolo","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology Weill Cornell Medicine\/New York\u2010Presbyterian Hospital  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara S","family":"Serafini","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology Weill Cornell Medicine\/New York\u2010Presbyterian Hospital  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Robert H. Lurie Cancer Center of Northwestern University Feinberg School of Medicine  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youbin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Robert H. Lurie Cancer Center of Northwestern University Feinberg School of Medicine  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Gerratana","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Centro di Riferimento Oncologico di Aviano (CRO), IRCCS  Aviano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew A.","family":"Davis","sequence":"additional","affiliation":[{"name":"Division of Oncology Washington University  St. Louis MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiping","family":"Liu","sequence":"additional","affiliation":[{"name":"Robert H. Lurie Cancer Center of Northwestern University Feinberg School of Medicine  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J","family":"Gradishar","sequence":"additional","affiliation":[{"name":"Robert H. Lurie Cancer Center of Northwestern University Feinberg School of Medicine  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Reduzzi","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology Weill Cornell Medicine\/New York\u2010Presbyterian Hospital  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Cristofanilli","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology Weill Cornell Medicine\/New York\u2010Presbyterian Hospital  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7796-5914","authenticated-orcid":false,"given":"Evi","family":"Lianidou","sequence":"additional","affiliation":[{"name":"Analysis of Circulating Tumor Cells, Laboratory of Analytical Chemistry, Department of Chemistry University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,27]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21763"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/ONCOLO\/OYAC045"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/S10549-013-2711-Y"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/OP.21.00707"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.25810"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15072185"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2024.11.009"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-020-00457-x"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMOA040766"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-24-3108"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22695"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2024.104483"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-25400-1"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCO.0000000000001168"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCO.0000000000000964"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-20-4037"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737159.2019.1631799"},{"key":"e_1_2_11_19_1","doi-asserted-by":"crossref","unstructured":"Bidard F. 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