{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T02:23:40Z","timestamp":1791599020454,"version":"4.3.4"},"reference-count":68,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"44","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,10,31]]},"abstract":"<jats:p>Overtreatment of patients with ductal carcinoma in situ (DCIS) is driven by a lack of a reliable prognostic biomarker. Widespread mammographic screening has resulted in a substantial increase in women diagnosed with DCIS. To improve patient risk stratification, we investigate circulating tumor cells (CTCs) as a biomarker for DCIS patients\u2019 biological aggressiveness and as an indicator of early dissemination. We apply microfluidics to enrich CTCs from 34 patients with DCIS and find a significantly higher concentration of CTCs compared to in healthy controls. We profile CTCs and matched DCIS tissues using single-cell RNA sequencing. We find that CTCs express higher clonal aberrations when compared to white blood cells from the same samples, and clonal comparisons between matched tissue and CTC samples provide evidence for an evolutionary bottleneck model. mRNA expression in CTC reveals EMT\/MET and immunoregulatory pathway regulation with a suggestion of racial differences. Last, we provide support for early dissemination in DCIS using a Mouse IntraDuctal model.<\/jats:p>","DOI":"10.1126\/sciadv.adz0187","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T17:58:36Z","timestamp":1761760716000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":5,"title":["Circulating tumor cells as predictive biomarkers in the risk stratification of DCIS: Evidence of early dissemination"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7492-7633","authenticated-orcid":true,"given":"Neha","family":"Nagpal","sequence":"first","affiliation":[{"name":"Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA."},{"name":"BioInterfaces Institute, University of Michigan, Ann Arbor, MI, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3654-9882","authenticated-orcid":true,"given":"Brittany","family":"Rupp","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA."},{"name":"BioInterfaces Institute, University of Michigan, Ann Arbor, MI, USA."},{"name":"Department of Oral and Craniofacial Molecular Biology, Virginia Commonwealth University, Richmond, VA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1721-0767","authenticated-orcid":true,"given":"Yan","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3710-7798","authenticated-orcid":true,"given":"Jamie","family":"Wagner","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Kansas Medical Center, Kansas City, KS, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1977-9459","authenticated-orcid":true,"given":"Kelsey","family":"Larson","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Kansas Medical Center, Kansas City, KS, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christa","family":"Balanoff","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Kansas Medical Center, Kansas City, KS, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7379-6025","authenticated-orcid":true,"given":"Allison","family":"Aripoli","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Kansas Medical Center, Kansas City, KS, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Huppe","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Kansas Medical Center, Kansas City, KS, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onalisa","family":"Winblad","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Kansas Medical Center, Kansas City, KS, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5426-0891","authenticated-orcid":true,"given":"Jessica","family":"Peterson","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Kansas Medical Center, Kansas City, KS, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly","family":"Hill","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Kansas Medical Center, Kansas City, KS, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0245-2047","authenticated-orcid":true,"given":"Camron","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Kansas Medical Center, Kansas City, KS, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8855-4133","authenticated-orcid":true,"given":"Carol","family":"Fabian","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, University of Kansas Medical Center, Kansas City, KS, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3987-9580","authenticated-orcid":true,"given":"Andrew K.","family":"Godwin","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0665-370X","authenticated-orcid":true,"given":"Timothy","family":"Fields","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4180-7727","authenticated-orcid":true,"given":"Max","family":"Wicha","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA."},{"name":"Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6281-2651","authenticated-orcid":true,"given":"Fariba","family":"Behbod","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1497-7977","authenticated-orcid":true,"given":"Sunitha","family":"Nagrath","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA."},{"name":"BioInterfaces Institute, University of Michigan, Ann Arbor, MI, USA."},{"name":"Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","unstructured":"Breast cancer in World Health Organization (2024)."},{"key":"e_1_3_2_3_2","unstructured":"Breast Cancer Facts & Stats in National Breast Cancer Foundation Inc. (2025)."},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.2214\/AJR.20.23314"},{"key":"e_1_3_2_5_2","unstructured":"J. DePolo DCIS (Ductal Carcinoma In Situ) (2024); breastcancer.org."},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molonc.2013.07.005"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-022-00512-y"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-020-05954-2"},{"key":"e_1_3_2_9_2","unstructured":"Understanding Ductal Carcinoma In Situ (DCIS) in Breast Cancer Research Foundation (2025)."},{"key":"e_1_3_2_10_2","unstructured":"Survival Rates for Breast Cancer in American Cancer Society (2025)."},{"key":"e_1_3_2_11_2","unstructured":"C. Helwick E. S. Hwang Optimizing the Management of DCIS The ASCO Post (2024)."},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25240-z"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/jncimonographs\/lgq039"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.25895"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-014-2898-6"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.12022"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2023.04.002"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.5820"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2017.08.012"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202000171"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31009-9"},{"key":"e_1_3_2_22_2","unstructured":"10x Genomics Fixation of Cells & Nuclei for Chromium Fixed RNA Profiling (2023)."},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/bcr2358"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa040766"},{"key":"e_1_3_2_25_2","first-page":"5145","article-title":"Real-time quantification of CK-19 mRNA-positive cells in peripheral blood of breast cancer patients using the lightcycler system","volume":"9","author":"Stathopoulou A.","year":"2003","unstructured":"A. Stathopoulou, A. Gizi, M. Perraki, S. Apostolaki, N. Malamos, D. Mavroudis, V. Georgoulias, E. S. Lianidou, Real-time quantification of CK-19 mRNA-positive cells in peripheral blood of breast cancer patients using the lightcycler system. Clin. Cancer Res. 9, 5145\u20135151 (2003).","journal-title":"Clin. Cancer Res."},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/dju066"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-2042"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-0378"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-08129-x"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06252-9"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2019.12.001"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-21-4145"},{"key":"e_1_3_2_33_2","unstructured":"T. Tickle I. Tirosh C. Georgescu M. Brown B. Haas inferCNV of the Trinity CTAT Project GitHub (2019)."},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2023.01.001"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0243928"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033788"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13058-024-01885-8"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2022.10.021"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells9030623"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom10111561"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1017\/erm.2017.6"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI164227"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2017.21"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21246-9"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-08480-y"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-41095-y"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0015624"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1186\/bcr3333"},{"key":"e_1_3_2_50_2","first-page":"2345","article-title":"Relationship between hematogenous tumor cell dissemination and cellular immunity in DCIS patients","volume":"36","author":"Gruber I. V.","year":"2016","unstructured":"I. V. Gruber, A. D. Hartkopf, M. Hahn, F.-A. Taran, A. Staebler, D. Wallwiener, S. Y. Brucker, J. Hanke, T. Fehm, Relationship between hematogenous tumor cell dissemination and cellular immunity in DCIS patients. Anticancer Res 36, 2345\u20132351 (2016).","journal-title":"Anticancer Res"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2025.217703"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2024.11.009"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1111\/his.14804"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-020-01152-5"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2017.00248"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2015.2510"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-050715-104920"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2024.2205"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2020.17124"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa022152"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa020989"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01082-3"},{"key":"e_1_3_2_63_2","unstructured":"S. A. Narod Treating DCIS: To Escalate or De-escalate? The ASCO Post (2024); https:\/\/ascopost.com\/issues\/april-25-2024\/treating-dcis-to-escalate-or-de-escalate\/."},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.m1570"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-20301-6_3"},{"key":"e_1_3_2_66_2","unstructured":"Triple-negative Breast Cancer American Cancer Society (2023)."},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.07.024"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2018-026797"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1200\/PO.19.00345"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.adz0187","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T18:00:40Z","timestamp":1761760840000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.adz0187"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,31]]},"references-count":68,"journal-issue":{"issue":"44","published-print":{"date-parts":[[2025,10,31]]}},"alternative-id":["10.1126\/sciadv.adz0187"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.adz0187","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,31]]},"assertion":[{"value":"2025-05-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadz0187"}}