{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T12:50:15Z","timestamp":1763988615415,"version":"build-2065373602"},"reference-count":20,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Current aftercare after early breast cancer overlooks recent evidence on circulating free tumor DNA (ctDNA). In this case report, we present a patient with low-risk hormone-receptor-positive breast cancer. ctDNA was first detected using a tumor-informed approach 12 months after the initial diagnosis and remained positive throughout adjuvant therapy with letrozole, while routine staging examinations showed no signs of relapse. Clinical relapse was ultimately identified nearly six years after the initial diagnosis, resulting in a lead time of four years and nine months. Current studies on ctDNA in the adjuvant setting have been conducted in high-risk cohorts and have shown a median molecular lead time of 8.9\u201312.4 months. Our study supports the need for large randomized clinical trials involving low-risk breast cancer patients to drive changes in clinical practice.<\/jats:p>","DOI":"10.3390\/ijms26178498","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T15:02:57Z","timestamp":1756825377000},"page":"8498","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Is Radiographic Aftercare Obsolete? How Testing Positive for ctDNA Can Be a Precedent for Late Relapse, Even in Low-Risk Hormone-Receptor-Positive Breast Cancer"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2831-1401","authenticated-orcid":false,"given":"Kerstin","family":"Pfister","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital Ulm, 89075 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophia","family":"Huesmann","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital Ulm, 89075 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelina","family":"Fink","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital Ulm, 89075 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4773-8067","authenticated-orcid":false,"given":"Thomas W. P.","family":"Friedl","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital Ulm, 89075 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franziska","family":"Mergel","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital Ulm, 89075 Ulm, Germany"},{"name":"Department of Gynecology and Obstetrics, SLK-Kliniken Heilbronn, 74078 Heilbronn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henning P.","family":"Sch\u00e4ffler","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital Ulm, 89075 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1227-1118","authenticated-orcid":false,"given":"Andreas","family":"Hartkopf","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s Health, T\u00fcbingen University, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9336-2267","authenticated-orcid":false,"given":"Stefan","family":"Lukac","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital Ulm, 89075 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2959-0580","authenticated-orcid":false,"given":"Kristina","family":"Veselinovic","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital Ulm, 89075 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Forca","family":"Mehmeti","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital Ulm, 89075 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathan","family":"Campbell","sequence":"additional","affiliation":[{"name":"NeoGenomics Babraham Research Campus, Cambridge CB22 3AT, UK"},{"name":"NeoGenomics Research Triangle Park, Durham, NC 27713, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christodoulos","family":"Pipinikas","sequence":"additional","affiliation":[{"name":"NeoGenomics Babraham Research Campus, Cambridge CB22 3AT, UK"},{"name":"NeoGenomics Research Triangle Park, Durham, NC 27713, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"Deininger","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, University Hospital Ulm, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9042-7806","authenticated-orcid":false,"given":"Ambros","family":"Beer","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, University Hospital Ulm, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8341-1722","authenticated-orcid":false,"given":"Stefanie","family":"Lorenz","sequence":"additional","affiliation":[{"name":"Department of Radiology, University Hospital Ulm, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7523-1979","authenticated-orcid":false,"given":"Meinrad","family":"Beer","sequence":"additional","affiliation":[{"name":"Department of Radiology, University Hospital Ulm, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2397-5041","authenticated-orcid":false,"given":"Lisa","family":"Wiesm\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital Ulm, 89075 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"Janni","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital Ulm, 89075 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Heublein","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital Ulm, 89075 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brigitte","family":"Rack","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital Ulm, 89075 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,1]]},"reference":[{"key":"ref_1","unstructured":"Robert Koch Institut (2024, December 10). Zentrum f\u00fcr Krebsregisterdaten. Available online: https:\/\/www.krebsdaten.de\/Krebs\/EN\/Content\/Cancer_sites\/Breast_cancer\/breast_cancer_node.html."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1001\/jama.1994.03510440053032","article-title":"Intensive diagnostic follow-up after treatment of primary breast cancer. A randomized trial. National Research Council Project on Breast Cancer follow-up","volume":"271","author":"Palli","year":"1994","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"The GIVIO Investigators (1994). Impact of follow-up testing on survival and health-related quality of life in breast cancer patients. A multicenter randomized controlled trial. The GIVIO Investigators. JAMA, 271, 1587\u20131592.","DOI":"10.1001\/jama.1994.03510440047031"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1038\/nm.1789","article-title":"Circulating mutant DNA to assess tumor dynamics","volume":"14","author":"Diehl","year":"2008","journal-title":"Nat. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1200\/JCO.2012.45.2011","article-title":"Liquid biopsies: Genotyping circulating tumor DNA","volume":"32","author":"Diaz","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4255","DOI":"10.1158\/1078-0432.CCR-18-3663","article-title":"Personalized Detection of Circulating Tumor DNA Antedates Breast Cancer Metastatic Recurrence","volume":"25","author":"Coombes","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1001\/jamaoncol.2019.1838","article-title":"Assessment of Molecular Relapse Detection in Early-Stage Breast Cancer","volume":"5","author":"Chopra","year":"2019","journal-title":"JAMA Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2408","DOI":"10.1200\/JCO.22.00908","article-title":"Circulating Tumor DNA and Late Recurrence in High-Risk Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer","volume":"40","author":"Santos","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1038\/s41388-018-0565-9","article-title":"EGFL6 promotes breast cancer by simultaneously enhancing cancer cell metastasis and stimulating tumor angiogenesis","volume":"38","author":"An","year":"2019","journal-title":"Oncogene"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4772","DOI":"10.1002\/jcb.29700","article-title":"lncRNA TTN-AS1 facilitates proliferation, invasion, and epithelial-mesenchymal transition of breast cancer cells by regulating miR-139-5p\/ZEB1 axis","volume":"121","author":"Fang","year":"2020","journal-title":"J. Cell Biochem."},{"key":"ref_11","unstructured":"(2025, August 19). AGO Komission Mamma AGO-Leitlinien Mammakarzinom. Available online: https:\/\/www.ago-online.de\/fileadmin\/ago-online\/downloads\/_leitlinien\/kommission_mamma\/2024\/Einzeldateien\/AGO_2024D_16_Nachsorge.pdf."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1056\/NEJMoa2305488","article-title":"Ribociclib plus Endocrine Therapy in Early Breast Cancer","volume":"390","author":"Slamon","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"102390","DOI":"10.1016\/j.esmoop.2024.102390","article-title":"Circulating tumor DNA for predicting recurrence in patients with operable breast cancer: A systematic review and meta-analysis","volume":"9","author":"Monteforte","year":"2024","journal-title":"ESMO Open"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"TPS620","DOI":"10.1200\/JCO.2024.42.16_suppl.TPS620","article-title":"The SURVIVE study: Liquid biopsy guided surveillance after intermediate- to high-risk early breast cancer","volume":"42","author":"Pfister","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1038\/s41416-022-01716-7","article-title":"Liquid BIOpsy for MiNimal RESidual DiSease Detection in Head and Neck Squamous Cell Carcinoma (LIONESS)-a personalised circulating tumour DNA analysis in head and neck squamous cell carcinoma","volume":"126","author":"Flach","year":"2022","journal-title":"Br. J. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1038\/s41591-022-02199-y","article-title":"High- or low-dose preoperative ipilimumab plus nivolumab in stage III urothelial cancer: The phase 1B NABUCCO trial","volume":"29","author":"Pipinikas","year":"2023","journal-title":"Nat. Med."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Voss, T., Ullius, A., Schonborn, M., and Oelmuller, U. (2021). Sensitivity assessment of workflows detecting rare circulating cell-free DNA targets: A study design proposal. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0253401"},{"key":"ref_18","unstructured":"(2024, December 10). Available online: https:\/\/kersnikova.org\/wp-content\/uploads\/2022\/03\/1.-Isolation-of-mononuclear-cells-_-basic-protocol_-GE-Healthcare.pdf."},{"key":"ref_19","unstructured":"(2024, December 10). Available online: https:\/\/www.sigmaaldrich.com\/DE\/de\/technical-documents\/protocol\/clinical-testing-and-diagnostics-manufacturing\/hematology\/recommended-standard-method."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/s41419-020-2531-z","article-title":"Deep sequencing of circulating tumor DNA detects molecular residual disease and predicts recurrence in gastric cancer","volume":"11","author":"Yang","year":"2020","journal-title":"Cell Death Dis."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/17\/8498\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:37:25Z","timestamp":1760035045000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/17\/8498"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,1]]},"references-count":20,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["ijms26178498"],"URL":"https:\/\/doi.org\/10.3390\/ijms26178498","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,9,1]]}}}