{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T01:18:23Z","timestamp":1793582303210,"version":"4.5.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2022,4,9]],"date-time":"2022-04-09T00:00:00Z","timestamp":1649462400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,4,9]],"date-time":"2022-04-09T00:00:00Z","timestamp":1649462400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Cancer Res Clin Oncol"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>Physical examinations and annual mammography (minimal follow-up) are as effective as laboratory\/imaging tests (intensive follow-up) in detecting breast cancer (BC) recurrence. This statement is now challenged by the availability of new diagnostic tools for asymptomatic cases. Herein, we analyzed current practices and circulating tumor DNA (ctDNA) in monitoring high-risk BC patients treated with curative intent in a comprehensive cancer center.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Patients and methods<\/jats:title>\n                <jats:p>Forty-two consecutive triple negative BC patients undergoing neoadjuvant therapy and surgery were prospectively enrolled. Data from plasma samples and surveillance procedures were analyzed to report the diagnostic pattern of relapsed cases, i.e., by symptoms, follow-up procedures and ctDNA.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Besides minimal follow-up, 97% and 79% of patients had at least 1 non-recommended imaging and laboratory tests for surveillance purposes. During a median follow-up of 5.1(IQR, 4.1\u20135.9) years, 13 events occurred (1 contralateral BC, 1 loco-regional recurrence, 10 metastases, and 1 death). Five recurrent cases were diagnosed by intensive follow-up, 5 by symptoms, and 2 incidentally. ctDNA antedated disseminated disease in all evaluable cases excepted two with bone-only and single liver metastases. The mean time from ctDNA detection to suspicious findings at follow-up imaging was 3.81(SD, 2.68), and to definitive recurrence diagnosis 8(SD, 2.98) months. ctDNA was undetectable in the absence of disease and in two suspected cases not subsequently confirmed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Some relapses are still symptomatic despite the extensive use of intensive follow-up. ctDNA is a specific test, sensitive enough to detect recurrence before other methods, suitable for clarifying equivocal imaging, and exploitable for salvage therapy in asymptomatic BC survivors.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00432-022-03990-7","type":"journal-article","created":{"date-parts":[[2022,4,9]],"date-time":"2022-04-09T08:02:39Z","timestamp":1649491359000},"page":"1543-1550","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Early stage breast cancer follow-up in real-world clinical practice: the added value of cell free circulating tumor DNA"],"prefix":"10.1007","volume":"148","author":[{"given":"E.","family":"La Rocca","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. C.","family":"De Santis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Silvestri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Ortolan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Valenti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Folli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. G.","family":"de Braud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. V.","family":"Bianchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. P.","family":"Scaperrotta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Apolone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. G.","family":"Daidone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Cappelletti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Pruneri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4666-8052","authenticated-orcid":false,"given":"S.","family":"Di Cosimo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,4,9]]},"reference":[{"issue":"6","key":"3990_CR1","doi-asserted-by":"publisher","first-page":"1502","DOI":"10.1245\/s10434-018-6359-z","volume":"25","author":"T Adesoye","year":"2018","unstructured":"Adesoye T, Schumacher JR, Neuman HB, Edge S, McKellar D, Winchester DP, Francescatti AB, Greenberg CC, Alliance ACS-CRP CCDR Breast Cancer Surveillance Working Group (2018) Use of breast imaging after treatment for locoregional breast cancer (AFT-01). Ann Surg Oncol 25(6):1502\u20131511","journal-title":"Ann Surg Oncol"},{"issue":"5","key":"3990_CR2","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1177\/030089161109700503","volume":"97","author":"S Barni","year":"2011","unstructured":"Barni S, Venturini M, Molino A et al (2011) Importance of adherence to guidelines in breast cancer clinical practice. The Italian experience (AIOM). Tumori 97(5):559\u2013563","journal-title":"Tumori"},{"issue":"8","key":"3990_CR3","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1093\/annonc\/mdz173","volume":"30","author":"F Cardoso","year":"2019","unstructured":"Cardoso F, Kyriakides S, Ohno S et al (2019) Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 30(8):1194\u20131220","journal-title":"Ann Oncol"},{"key":"3990_CR4","doi-asserted-by":"crossref","unstructured":"Cardoso F, Paluch-Shimon S, Senkus E (2020) 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5)\u2020 [Internet]. Ann Oncol 31(12):1623\u20131649","DOI":"10.1016\/j.annonc.2020.09.010"},{"key":"3990_CR5","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1200\/JCO.2015.62.3504","volume":"34","author":"M Colleoni","year":"2016","unstructured":"Colleoni M, Sun Z, Price KN et al (2016) Annual hazard rates of recurrence for breast cancer during 24 years of follow-up: results from the international breast cancer study group trials I to V. J Clin Oncol 34:927\u2013935","journal-title":"J Clin Oncol"},{"issue":"14","key":"3990_CR6","doi-asserted-by":"publisher","first-page":"4255","DOI":"10.1158\/1078-0432.CCR-18-3663","volume":"25","author":"RC Coombes","year":"2019","unstructured":"Coombes RC, Page K, Salari R et al (2019) Personalized detection of circulating tumor DNA antedates breast cancer metastatic recurrence. Clin Cancer Res 25(14):4255\u20134263","journal-title":"Clin Cancer Res"},{"issue":"13","key":"3990_CR7","doi-asserted-by":"publisher","first-page":"6537","DOI":"10.2147\/CMAR.S300869","volume":"20","author":"G Cuy\u00fan Carter","year":"2021","unstructured":"Cuy\u00fan Carter G, Mohanty M, Stenger K et al (2021) Prognostic factors in hormone receptor-positive\/human epidermal growth factor receptor 2-negative (HR+\/HER2\u2212) advanced breast cancer: a systematic literature review. Cancer Manag Res 20(13):6537\u20136566","journal-title":"Cancer Manag Res"},{"issue":"4","key":"3990_CR8","doi-asserted-by":"publisher","first-page":"100203","DOI":"10.1016\/j.esmoop.2021.100203","volume":"6","author":"L De Cock","year":"2021","unstructured":"De Cock L, Heylen J, Wildiers A et al (2021) Detection of secondary metastatic breast cancer by measurement of plasma CA 153. ESMO Open 6(4):100203. https:\/\/doi.org\/10.1016\/j.esmoop.2021.100203","journal-title":"ESMO Open"},{"issue":"Suppl 3","key":"3990_CR9","doi-asserted-by":"publisher","first-page":"iii28","DOI":"10.1093\/annonc\/mdz096.005","volume":"30","author":"S Di Cosimo","year":"2019","unstructured":"Di Cosimo S, Appierto V, Ortolan E et al (2019) Circulating tumor DNA and disease recurrence in early stage breast cancer: From a case-control study to a prospective longitudinal trial. Ann Oncol 30(Suppl 3):iii28","journal-title":"Ann Oncol"},{"issue":"10","key":"3990_CR10","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1001\/jamaoncol.2019.1838","volume":"5","author":"I Garcia-Murillas","year":"2019","unstructured":"Garcia-Murillas I, Chopra N, Comino-M\u00e9ndez I et al (2019) Assessment of molecular relapse detection in early-stage breast cancer. JAMA Oncol 5(10):1473\u20131478","journal-title":"JAMA Oncol"},{"issue":"24","key":"3990_CR11","doi-asserted-by":"publisher","first-page":"4316","DOI":"10.1002\/cncr.28363","volume":"119","author":"EE Hahn","year":"2013","unstructured":"Hahn EE, Hays RD, Kahn KL, Litwin MS, Ganz PA (2013) Use of imaging and biomarker tests for posttreatment care of early-stage breast cancer survivors. Cancer 119(24):4316\u20134324","journal-title":"Cancer"},{"issue":"3","key":"3990_CR12","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1200\/JCO.2002.20.3.620","volume":"20","author":"GN Hortobagyi","year":"2002","unstructured":"Hortobagyi GN (2002) Can we cure limited metastatic breast cancer? J Clin Oncol 20(3):620\u2013623","journal-title":"J Clin Oncol"},{"issue":"5","key":"3990_CR13","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1038\/s41571-020-00457-x","volume":"18","author":"M Ignatiadis","year":"2021","unstructured":"Ignatiadis M, Sledge GW, Jeffrey SS (2021) Liquid biopsy enters the clinic\u2014implementation issues and future challenges. Nat Rev Clin Oncol 18(5):297\u2013312","journal-title":"Nat Rev Clin Oncol"},{"issue":"9","key":"3990_CR14","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1200\/JCO.2006.08.6876","volume":"25","author":"NL Keating","year":"2007","unstructured":"Keating NL, Landrum MB, Guadagnoli E, Winer EP, Ayanian JZ (2007) Surveillance testing among survivors of early-stage breast cancer. J Clin Oncol 25(9):1074\u20131081","journal-title":"J Clin Oncol"},{"issue":"5","key":"3990_CR15","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1016\/j.breast.2014.06.017","volume":"23","author":"A Llombart-Cussac","year":"2014","unstructured":"Llombart-Cussac A, Pivot X, Biganzoli L et al (2014) A prognostic factor index for overall survival in patients receiving first-line chemotherapy for HER2-negative advanced breast cancer: an analysis of the ATHENA trial. Breast 23(5):656\u2013662","journal-title":"Breast"},{"key":"3990_CR16","doi-asserted-by":"publisher","first-page":"1750","DOI":"10.1016\/S0140-6736(20)32381-3","volume":"397","author":"S Loibl","year":"2021","unstructured":"Loibl S, Poortmans P, Morrow M, Denkert C, Curigliano G (2021) Breast cancer. Lancet 397:1750\u20131769","journal-title":"Lancet"},{"issue":"1","key":"3990_CR17","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1007\/s11864-013-0265-1","volume":"15","author":"JM Matro","year":"2014","unstructured":"Matro JM, Goldstein LJ (2014) How do I follow patients with early breast cancer after completing adjuvant therapy. Curr Treat Options Oncol 15(1):63\u201378","journal-title":"Curr Treat Options Oncol"},{"key":"3990_CR18","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1002\/pon.1481","volume":"18","author":"A Mehnert","year":"2009","unstructured":"Mehnert A, Berg P, Henrich G, Herschbach P (2009) Fear of cancer progression and cancer-related intrusive cognitions in breast cancer survivors. Psychooncology 18:1273\u20131280","journal-title":"Psychooncology"},{"key":"3990_CR19","doi-asserted-by":"publisher","first-page":"1631","DOI":"10.1200\/JCO.2017.76.8671","volume":"36","author":"JD Merker","year":"2018","unstructured":"Merker JD, Oxnard GR, Compton C et al (2018) Circulating tumor DNA analysis in patients with cancer: American Society of Clinical Oncology and College of American Pathologists Joint Review. J Clin Oncol 36:1631\u20131641","journal-title":"J Clin Oncol"},{"key":"3990_CR20","first-page":"1768","volume":"5","author":"I Moschetti","year":"2016","unstructured":"Moschetti I, Cinquini M, Lambertini M, Levaggi A, Liberato A (2016) Follow-up strategies for women treated for early breast cancer. Cochrane Database Syst Rev 5:1768","journal-title":"Cochrane Database Syst Rev"},{"issue":"4","key":"3990_CR21","doi-asserted-by":"publisher","first-page":"94063","DOI":"10.1371\/journal.pone.0094063","volume":"9","author":"C Natoli","year":"2014","unstructured":"Natoli C, Brocco D, Sperduti I et al (2014) Breast cancer \u201ctailored follow-up\u201d in Italian oncology units: a web-based survey. PLoS ONE 9(4):94063","journal-title":"PLoS ONE"},{"issue":"2","key":"3990_CR22","doi-asserted-by":"publisher","first-page":"100086","DOI":"10.1016\/j.esmoop.2021.100086","volume":"6","author":"E Ortolan","year":"2021","unstructured":"Ortolan E, Appierto V, Silvestri M et al (2021) Blood-based genomics of triple-negative breast cancer progression in patients treated with neoadjuvant chemotherapy. ESMO Open 6(2):100086","journal-title":"ESMO Open"},{"key":"3990_CR23","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1093\/jnci\/djq029","volume":"102","author":"O Pagani","year":"2010","unstructured":"Pagani O, Senkus E, Wood W et al (2010) International guidelines for management of metastatic breast cancer: can metastatic breast cancer be cured? J Natl Cancer Inst 102:456\u2013463","journal-title":"J Natl Cancer Inst"},{"key":"3990_CR24","doi-asserted-by":"publisher","DOI":"10.1200\/PO.20.00522","author":"K Page","year":"2021","unstructured":"Page K, Martinson LJ, Fernandez-Garcia D et al (2021) Circulating tumor DNA profiling from breast cancer screening through to metastatic disease. JCO Precis Oncol. https:\/\/doi.org\/10.1200\/PO.20.00522","journal-title":"JCO Precis Oncol"},{"key":"3990_CR25","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.1001\/jama.281.17.1586","volume":"281","author":"D Palli","year":"1999","unstructured":"Palli D, Russo A, Saieva C et al (1999) Intensive vs clinical follow-up after treatment of primary breast cancer: 10-year update of a randomized trial. National Research Council Project on Breast Cancer Follow-up. JAMA 281:1586","journal-title":"JAMA"},{"issue":"49","key":"3990_CR26","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1093\/jncimonographs\/lgu023","volume":"2014","author":"BA Rabin","year":"2014","unstructured":"Rabin BA, Ellis JL, Steiner JF et al (2014) Health-care utilization by prognosis profile in a managed care setting: using the surveillance, epidemiology and end results cancer survival calculator SEER*CSC. J Natl Cancer Inst Monogr 2014(49):275\u2013281","journal-title":"J Natl Cancer Inst Monogr"},{"key":"3990_CR27","doi-asserted-by":"publisher","first-page":"1593","DOI":"10.1001\/jama.271.20.1593","volume":"271","author":"M Rosselli Del Turco","year":"1994","unstructured":"Rosselli Del Turco M, Palli D, Cariddi A et al (1994) Intensive diagnostic follow-up after treatment of primary breast cancer. A randomized trial National Research Council Project on Breast Cancer follow-up. JAMA 271:1593\u20131597","journal-title":"JAMA"},{"issue":"6","key":"3990_CR28","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1200\/JCO.2015.64.3809","volume":"34","author":"CD Runowicz","year":"2016","unstructured":"Runowicz CD, Leach CR, Henry NL et al (2016) American Cancer Society\/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline. J Clin Oncol 34(6):611\u2013635","journal-title":"J Clin Oncol"},{"issue":"20","key":"3990_CR29","doi-asserted-by":"publisher","first-page":"1587","DOI":"10.1001\/jama.1994.03510440047031","volume":"271","author":"The GIVIO Investigators","year":"1994","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. JAMA 271(20):1587\u20131592","journal-title":"JAMA"},{"key":"3990_CR30","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1002\/pon.2070","volume":"21","author":"B Thewes","year":"2012","unstructured":"Thewes B, Butow P, Zachariae R, Christensen S, Simard S, Gotay C (2012) Fear of cancer recurrence: a systematic literature review of self-report measures. Psychooncology 21:571\u2013587","journal-title":"Psychooncology"},{"issue":"6","key":"3990_CR31","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1038\/nrclinonc.2011.44","volume":"8","author":"RR Weichselbaum","year":"2011","unstructured":"Weichselbaum RR, Hellman S (2011) Oligometastases revisited. Nat Rev Clin Oncol 8(6):378\u2013382","journal-title":"Nat Rev Clin Oncol"},{"issue":"6","key":"3990_CR32","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1093\/annonc\/mdm573","volume":"19","author":"SH Yang","year":"2008","unstructured":"Yang SH, Yang KH, Li YP et al (2008) Breast conservation therapy for stage I or stage II breast cancer: a meta-analysis of randomized controlled trials. Ann Oncol 19(6):1039\u20131044","journal-title":"Ann Oncol"}],"container-title":["Journal of Cancer Research and Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00432-022-03990-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00432-022-03990-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00432-022-03990-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T07:07:16Z","timestamp":1652771236000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00432-022-03990-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,9]]},"references-count":32,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,6]]}},"alternative-id":["3990"],"URL":"https:\/\/doi.org\/10.1007\/s00432-022-03990-7","relation":{},"ISSN":["0171-5216","1432-1335"],"issn-type":[{"value":"0171-5216","type":"print"},{"value":"1432-1335","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,9]]},"assertion":[{"value":"8 March 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 March 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 April 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"ELR, MCD, MS, EO, MV, SF, GVB, GS, GA, MGD, and VC: none; FGdB: speakers bureau honoraria from BMS, Eli Lilly, Roche, Amgen, AstraZeneca, Gentili, Fondazione Menarini, Novartis, MSD, Ignyta, Bayer, Noema SRL, ACCMED, DEPHAFORUM SRL, Nadirex, Roche, Biotechspert Ltd., PriME Oncology, Pfizer, consultant\/advisory board fees from BMS, Tiziana Life Sciences, Celgene, Novartis, Servier, Phanm Research Associated, Daiichi Sankyo, Ignyta, Amgen, Pfizer, Roche, Teogarms, and Pierre Fabre; GP: honoraria from Roche, GSK, Genomic Health, and Hybrid Genetic; SDC:\u00a0consulting fees from Pierre-Fabre, IQVIA.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This study was performed in line with the principles of the Declaration of Helsinki.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}}]}}