{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T02:23:57Z","timestamp":1791599037305,"version":"4.3.4"},"reference-count":41,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"840","funder":[{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","award":["CSCC-Team-23-980420-01-CSCC"],"award-info":[{"award-number":["CSCC-Team-23-980420-01-CSCC"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","award":["23-980420-01-CSCC"],"award-info":[{"award-number":["23-980420-01-CSCC"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["NCI CA060553"],"award-info":[{"award-number":["NCI CA060553"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA245699"],"award-info":[{"award-number":["R01CA245699"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA298232"],"award-info":[{"award-number":["R01CA298232"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI167272"],"award-info":[{"award-number":["R01AI167272"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005410","name":"American-Italian Cancer Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005410","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2026,3,11]]},"abstract":"<jats:p>Metastasis is the leading cause of death in patients with breast cancer (BC), but the mechanisms underlying metastasis formation are still poorly understood. Circulating tumor cells (CTCs) are considered the main seed of metastasis with demonstrated prognostic impact in patients with BC. They are conventionally identified as cells positive for epithelial markers and lacking leukocyte markers. Nonetheless, circulating cells expressing both markers [dual-positive cells (DPcells)] have been reported but poorly investigated. Here, we evaluated, in a cohort of 340 patients with advanced BC, the prognostic impact of DPcells, showing their association with worse survival, particularly in patients with less than five CTCs. Their prognostic value varied among BC subtypes, with greater relevance observed in triple-negative and HER2-positive BC. Moreover, by performing single-cell genomic profiling of DPcells isolated from patients, we detected genomic aberrations in 28 and 93% of analyzed DPcells and CTCs, respectively. In vivo, DPcells were detected only in the blood of immunocompetent but not immunodeficient mice and no differences in the lung metastatic colonization ability of DPcells versus control cancer cells were observed. Our findings highlight the importance of studying this overlooked subpopulation of CTCs as a prognostic biomarker in BC, which might be particularly important in specific BC subtypes. Moreover, our results support the malignancy and metastasis-forming capability of DPcells and underline the need for future studies better defining the origin of these cells.<\/jats:p>","DOI":"10.1126\/scitranslmed.adw7698","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T17:58:12Z","timestamp":1773251892000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":5,"title":["Dual-positive CTCs in patients with advanced breast cancer show metastatic potential and prognostic value"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0514-0152","authenticated-orcid":true,"given":"Carolina","family":"Reduzzi","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Hematology-Oncology, Weill Cornell Medicine, New York, NY 10021, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5042-6550","authenticated-orcid":true,"given":"Eleonora","family":"Nicol\u00f2","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology-Oncology, Weill Cornell Medicine, New York, NY 10021, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8313-4834","authenticated-orcid":true,"given":"Lorenzo","family":"Gerratana","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Udine, Udine 33100, Italy."},{"name":"Department of Medical Oncology, CRO Aviano, National Cancer Institute, IRCCS, Aviano 33081, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren L.","family":"Ozimski","sequence":"additional","affiliation":[{"name":"Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology (ETH) Zurich, Zurich 8049, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8283-9130","authenticated-orcid":true,"given":"Marco","family":"Silvestri","sequence":"additional","affiliation":[{"name":"Department of Advanced Diagnostics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youbin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4604-1620","authenticated-orcid":true,"given":"David","family":"Scholten","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9192-9170","authenticated-orcid":true,"given":"Mara S.","family":"Serafini","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology-Oncology, Weill Cornell Medicine, New York, NY 10021, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4037-3402","authenticated-orcid":true,"given":"Maroua","family":"Manai","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA."},{"name":"Pasteur Institute of Tunis, University of Tunis El Manar, Tunis 1002, Tunisia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9155-425X","authenticated-orcid":true,"given":"Paolo","family":"D\u2019Amico","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1979-5020","authenticated-orcid":true,"given":"Elisabetta","family":"Molteni","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology-Oncology, Weill Cornell Medicine, New York, NY 10021, USA."},{"name":"Department of Medicine, University of Udine, Udine 33100, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8949-2296","authenticated-orcid":true,"given":"Nadia","family":"Bayou","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology-Oncology, Weill Cornell Medicine, New York, NY 10021, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3738-6715","authenticated-orcid":true,"given":"Brenno","family":"Past\u00f2","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology-Oncology, Weill Cornell Medicine, New York, NY 10021, USA."},{"name":"Department of Medicine, University of Udine, Udine 33100, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5916-8516","authenticated-orcid":true,"given":"Massimo","family":"Saini","sequence":"additional","affiliation":[{"name":"Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology (ETH) Zurich, Zurich 8049, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0447-9967","authenticated-orcid":true,"given":"Andrew A.","family":"Davis","sequence":"additional","affiliation":[{"name":"Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4666-8052","authenticated-orcid":true,"given":"Serena","family":"Di Cosimo","sequence":"additional","affiliation":[{"name":"Department of Advanced Diagnostics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Cappelletti","sequence":"additional","affiliation":[{"name":"Department of Advanced Diagnostics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4822-7995","authenticated-orcid":true,"given":"Huiping","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA."},{"name":"Department of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA."},{"name":"Chan Zuckerberg Biohub Chicago, Chicago, IL 60642, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"Gradishar","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9579-6918","authenticated-orcid":true,"given":"Nicola","family":"Aceto","sequence":"additional","affiliation":[{"name":"Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology (ETH) Zurich, Zurich 8049, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4194-7175","authenticated-orcid":true,"given":"Massimo","family":"Cristofanilli","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology-Oncology, Weill Cornell Medicine, New York, NY 10021, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2018.12.004"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1228522"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-017-4372-8"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0144535"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/bcr3622"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0099409"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201010021"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1012539107"},{"key":"e_1_3_2_10_2","first-page":"100","article-title":"Individual profiling of circulating tumor cell composition in patients with non-small cell lung cancer receiving platinum based treatment","volume":"3","author":"Nel I.","year":"2014","unstructured":"I. Nel, U. Jehn, T. Gauler, A. C. Hoffmann, Individual profiling of circulating tumor cell composition in patients with non-small cell lung cancer receiving platinum based treatment. Transl. Lung Cancer Res. 3, 100\u2013106 (2014).","journal-title":"Transl. Lung Cancer Res."},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14194617"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1313594110"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aat7828"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-021-10379-2"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.1095839"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0134320"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-93053-7"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2019.10.008"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-13-0896"},{"key":"e_1_3_2_20_2","first-page":"623","article-title":"Fusion hybrids with macrophage and melanoma cells up-regulate N-acetylglucosaminyltransferase V, \u03b21-6 branching, and metastasis","volume":"12","author":"Chakraborty A. K.","year":"2001","unstructured":"A. K. Chakraborty, J. Pawelek, Y. Ikeda, E. Miyoshi, N. Kolesnikova, Y. Funasaka, M. Ichihashi, N. Taniguchi, Fusion hybrids with macrophage and melanoma cells up-regulate N-acetylglucosaminyltransferase V, \u03b21-6 branching, and metastasis. Cell Growth Differ. 12, 623\u2013630 (2001).","journal-title":"Cell Growth Differ."},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.3892\/or.2014.3264"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2020.1773204"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0087893"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2371"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0184451"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29455"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergen.2021.05.009"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0168581"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.AM2023-2301"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bmt.1704939"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature25432"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0750-6"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/bs.acc.2015.12.005"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.19320"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006530"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb0508-503"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.15-271098"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0915-y"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04875-y"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.23687"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.175141.114"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/hvac019"}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.adw7698","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T17:58:38Z","timestamp":1773683918000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.adw7698"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,11]]},"references-count":41,"journal-issue":{"issue":"840","published-print":{"date-parts":[[2026,3,11]]}},"alternative-id":["10.1126\/scitranslmed.adw7698"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.adw7698","relation":{},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,11]]},"assertion":[{"value":"2025-02-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-03","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadw7698"}}