{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T06:36:18Z","timestamp":1773815778828,"version":"3.50.1"},"reference-count":31,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["RF 2018 12366921"],"award-info":[{"award-number":["RF 2018 12366921"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Circulating microRNAs (miRNAs) are promising minimally invasive biomarkers for cancer risk assessment, yet prospective evidence for breast cancer (BC) remains limited. We conducted a nested case\u2013control study within a prospective cohort to examine whether pre-diagnostic circulating miRNAs are associated with subsequent BC risk and to explore their potential relevance in prospective population-based settings. Baseline serum from 160 women (80 incident BC cases; 80 matched controls) was analyzed, with a median time to diagnosis of 8.9 years. Eight candidate miRNAs were quantified by droplet digital PCR (ddPCR) and normalized to miR-484. Group differences were evaluated by non-parametric tests, and odds ratios for BC were estimated using logistic regression models adjusted for established risk factors, with Bonferroni correction for multiple testing. Cases and controls were comparable at baseline. Among the candidates, lower circulating miR-181 levels showed a suggestive inverse association with BC risk in fully adjusted models, while lower Let7 levels showed only a non-significant, hypothesis-generating inverse trend that did not survive Bonferroni correction. No other miRNA displayed clear associations with BC risk. These findings, while preliminary, support further large-scale prospective investigations specifically designed to assess predictive performance and external validation. employing standardized pre-analytical and analytical protocols, repeated sampling, and independent replication\/external validation to clarify the etiologic relevance and potential risk-prediction value of circulating miRNAs for BC.<\/jats:p>","DOI":"10.3390\/ijms27062706","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T09:35:57Z","timestamp":1773740157000},"page":"2706","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Circulating microRNAs as Early Biomarkers of Breast Cancer: A Nested Case-Control Study Within a Prospective Cohort in Italy"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9609-3681","authenticated-orcid":false,"given":"Lisa","family":"Padroni","sequence":"first","affiliation":[{"name":"Department of Clinical and Biological Sciences, Centre for Biostatistics, Epidemiology, and Public Health (C-BEPH), University of Turin, 10043 Orbassano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giorgia","family":"Marmiroli","sequence":"additional","affiliation":[{"name":"Unit of Cancer Epidemiology, Department of Medical Sciences, University of Turin, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2167-9270","authenticated-orcid":false,"given":"Laura","family":"De Marco","sequence":"additional","affiliation":[{"name":"Unit of Cancer Epidemiology, Citt\u00e0 Della Salute e Della Scienza University-Hospital and Center for Cancer Prevention (CPO), Via Santena 7, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Fiano","sequence":"additional","affiliation":[{"name":"Unit of Cancer Epidemiology, Department of Medical Sciences, University of Turin, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2262-1102","authenticated-orcid":false,"given":"Saverio","family":"Caini","sequence":"additional","affiliation":[{"name":"Cancer Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), 50139 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Agnoli","sequence":"additional","affiliation":[{"name":"Epidemiology and Prevention Unit, Department of Epidemiology and Data Science, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7351-8634","authenticated-orcid":false,"given":"Claudia","family":"Vener","sequence":"additional","affiliation":[{"name":"Epidemiology and Prevention Unit, Department of Epidemiology and Data Science, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2387-4125","authenticated-orcid":false,"given":"Vittorio","family":"Simeon","sequence":"additional","affiliation":[{"name":"Medical Statistics Unit, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"Panico","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, School of Medicine, Federico II University, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6530-4326","authenticated-orcid":false,"given":"Luca","family":"Manfredi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, Centre for Biostatistics, Epidemiology, and Public Health (C-BEPH), University of Turin, 10043 Orbassano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2185-2179","authenticated-orcid":false,"given":"Lorenzo","family":"Milani","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, Centre for Biostatistics, Epidemiology, and Public Health (C-BEPH), University of Turin, 10043 Orbassano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8749-9737","authenticated-orcid":false,"given":"Fulvio","family":"Ricceri","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, Centre for Biostatistics, Epidemiology, and Public Health (C-BEPH), University of Turin, 10043 Orbassano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8008-5096","authenticated-orcid":false,"given":"Carlotta","family":"Sacerdote","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Eastern Piedmont, Via Solaroli 17, 28100 Novara, Italy"},{"name":"Unit of Epidemiology, Local Health Unit of Novara, Viale Roma, 7, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,16]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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