{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T07:09:05Z","timestamp":1780988945808,"version":"3.54.1"},"reference-count":18,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["RFPS-2006-1-339898"],"award-info":[{"award-number":["RFPS-2006-1-339898"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001006","name":"Breast Cancer Research Foundation","doi-asserted-by":"publisher","award":["PPI-23-002"],"award-info":[{"award-number":["PPI-23-002"]}],"id":[{"id":"10.13039\/100001006","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020581","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["IG 2008"],"award-info":[{"award-number":["IG 2008"]}],"id":[{"id":"10.13039\/100020581","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Italian League Against Cancer","award":["LILT 7-08"],"award-info":[{"award-number":["LILT 7-08"]}]},{"name":"Galliera Hospital"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Despite the proven efficacy of tamoxifen in breast cancer prevention, its uptake remains limited due to concerns over side effects. A phase 3 trial showed that low-dose tamoxifen (5\u2009mg\/d for 3\u2009years) substantially reduces recurrence with minimal toxicity. After 10\u2009years of follow-up, we observed no clinically significant differences in benign gynecological or breast events between the tamoxifen and placebo arms. The uterus was the most frequently affected site (30 cases per arm), followed by the breast (18 cases) and ovary (5 cases vs 3 cases for tamoxifen and placebo, respectively). Endometrial polyps were similarly distributed. Endometrial thickness remained stable in premenopausal women and showed only a mild, non\u2013clinically significant increase in postmenopausal women on tamoxifen (approximately 1.5\u2009mm). Compared with data on standard-dose tamoxifen, rates of benign events were lower. These findings reinforce the favorable safety profile of low-dose tamoxifen.<\/jats:p>","DOI":"10.1093\/jnci\/djaf250","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T11:44:25Z","timestamp":1756295065000},"page":"1115-1119","source":"Crossref","is-referenced-by-count":1,"title":["Effect of low-dose tamoxifen on benign gynecological and breast conditions in a phase 3 trial in noninvasive breast cancer"],"prefix":"10.1093","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9907-3299","authenticated-orcid":false,"given":"Alessio","family":"Carbone","sequence":"first","affiliation":[{"name":"EO Ospedali Galliera , Genoa,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5913-9258","authenticated-orcid":false,"given":"Martino","family":"Oliva","sequence":"additional","affiliation":[{"name":"EO Ospedali Galliera , Genoa,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7908-0626","authenticated-orcid":false,"given":"Matteo","family":"Puntoni","sequence":"additional","affiliation":[{"name":"Clinical and Epidemiological Research Unit, University Hospital of Parma , Parma,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1915-1688","authenticated-orcid":false,"given":"Aliana","family":"Guerrieri-Gonzaga","sequence":"additional","affiliation":[{"name":"European Institute of Oncology IRCCS , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0767-0026","authenticated-orcid":false,"given":"Irene Maria","family":"Briata","sequence":"additional","affiliation":[{"name":"EO Ospedali Galliera , Genoa,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2162-4002","authenticated-orcid":false,"given":"Matteo","family":"Lazzeroni","sequence":"additional","affiliation":[{"name":"European Institute of Oncology IRCCS , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2945-4108","authenticated-orcid":false,"given":"Davide","family":"Serrano","sequence":"additional","affiliation":[{"name":"European Institute of Oncology IRCCS , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9525-6070","authenticated-orcid":false,"given":"Livia","family":"Giordano","sequence":"additional","affiliation":[{"name":"Azienda Ospedaliera-Universitaria Citt\u00e0 della Salute e della Scienza , Torino,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7189-6893","authenticated-orcid":false,"given":"Maria","family":"Digennaro","sequence":"additional","affiliation":[{"name":"IRCCS, Istituto Tumori \u201cGiovanni Paolo II,\u201d Bari,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8950-8561","authenticated-orcid":false,"given":"Laura","family":"Cortesi","sequence":"additional","affiliation":[{"name":"Azienda Ospedaliera-Universitaria Policlinico di Modena , Modena,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3507-5407","authenticated-orcid":false,"given":"Francesco","family":"Millo","sequence":"additional","affiliation":[{"name":"Ospedali Riuniti ASL AL\u2014Ospedale SS Antonio e Margherita , Tortona, AL,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5800-1602","authenticated-orcid":false,"given":"Katia","family":"Cagossi","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, \u201cB. Ramazzini\u201d Hospital, Carpi ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Aprile","sequence":"additional","affiliation":[{"name":"Department of Oncology, San Bortolo General Hospital, ULSS8 Berica , Vicenza,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4959-579X","authenticated-orcid":false,"given":"Patrizia","family":"Serra","sequence":"additional","affiliation":[{"name":"IRCCS Istituto Romagnolo per lo Studio dei Tumori \u201cDino Amadori\u201d\u2014IRST S.r.l. , Meldola, FC,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Gallerani","sequence":"additional","affiliation":[{"name":"Aziende Socio Sanitarie Territoriale dei Sette Laghi , Varese,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3589-2128","authenticated-orcid":false,"given":"Bernardo","family":"Bonanni","sequence":"additional","affiliation":[{"name":"European Institute of Oncology IRCCS , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2635-4491","authenticated-orcid":false,"given":"Andrea","family":"DeCensi","sequence":"additional","affiliation":[{"name":"EO Ospedali Galliera , Genoa,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,8,29]]},"reference":[{"key":"2026060902504118600_djaf250-B1","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1093\/jnci\/90.18.1371","article-title":"Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study","volume":"90","author":"Fisher","year":"1998","journal-title":"J Natl Cancer Inst"},{"key":"2026060902504118600_djaf250-B2","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1016\/S0140-6736(13)62292-8","article-title":"Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial","volume":"383","author":"Cuzick","year":"2014","journal-title":"Lancet"},{"key":"2026060902504118600_djaf250-B3","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1093\/annonc\/mdv590","article-title":"Factors affecting uptake and adherence to breast cancer chemoprevention: a systematic review and meta-analysis","volume":"27","author":"Smith","year":"2016","journal-title":"Ann Oncol"},{"key":"2026060902504118600_djaf250-B4","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1007\/s10549-012-2089-2","article-title":"Use of tamoxifen and raloxifene for breast cancer chemoprevention in 2010","volume":"134","author":"Waters","year":"2012","journal-title":"Breast Cancer Res Treat"},{"key":"2026060902504118600_djaf250-B5","doi-asserted-by":"publisher","first-page":"3152","DOI":"10.1200\/JCO.19.01472","article-title":"Use of endocrine therapy for breast cancer risk reduction: ASCO clinical practice guideline update","volume":"37","author":"Visvanathan","year":"2019","journal-title":"J Clin Oncol"},{"key":"2026060902504118600_djaf250-B6","doi-asserted-by":"publisher","first-page":"1629","DOI":"10.1200\/JCO.18.01779","article-title":"Randomized placebo controlled trial of low-dose tamoxifen to prevent local and contralateral recurrence in breast intraepithelial neoplasia","volume":"37","author":"DeCensi","year":"2019","journal-title":"J Clin Oncol"},{"key":"2026060902504118600_djaf250-B7","doi-asserted-by":"publisher","first-page":"3116","DOI":"10.1200\/JCO.22.02900","article-title":"Randomized placebo controlled trial of low-dose tamoxifen to prevent recurrence in breast noninvasive neoplasia: a 10-year follow-up of TAM-01 study","volume":"41","author":"Lazzeroni","year":"2023","journal-title":"J Clin Oncol"},{"key":"2026060902504118600_djaf250-B8","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1007\/s10549-022-06577-5","article-title":"Initiation and tolerance of chemoprevention among women with high-risk breast lesions: the potential of low-dose tamoxifen","volume":"193","author":"Bychkovsky","year":"2022","journal-title":"Breast Cancer Res Treat"},{"key":"2026060902504118600_djaf250-B9","doi-asserted-by":"publisher","first-page":"331","DOI":"10.6004\/jnccn.2024.0035","article-title":"Breast cancer, version 3.2024, NCCN clinical practice guidelines in oncology","volume":"22","author":"Gradishar","year":"2024","journal-title":"J Natl Compr Canc Netw"},{"key":"2026060902504118600_djaf250-B10","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1158\/1940-6207.CAPR-24-0324","article-title":"Improved uptake and adherence to risk-reducing medication with the use of low-dose tamoxifen in patients at high risk for breast cancer","volume":"17","author":"Cornell","year":"2024","journal-title":"Cancer Prev Res (Phila)"},{"key":"2026060902504118600_djaf250-B11","doi-asserted-by":"publisher","first-page":"970","DOI":"10.1016\/j.annonc.2023.08.017","article-title":"Understanding breast cancer complexity to improve patient outcomes: the St Gallen International Consensus Conference for the Primary Therapy of Individuals with Early Breast Cancer 2023","volume":"34","author":"Curigliano","year":"2023","journal-title":"Ann Oncol"},{"key":"2026060902504118600_djaf250-B12","doi-asserted-by":"publisher","first-page":"1230","DOI":"10.1016\/j.ajog.2004.12.083","article-title":"Benign gynecologic conditions among participants in the Breast Cancer Prevention Trial","volume":"192","author":"Chalas","year":"2005","journal-title":"Am J Obstet Gynecol"},{"key":"2026060902504118600_djaf250-B13","doi-asserted-by":"publisher","first-page":"535.e1-5","DOI":"10.1016\/j.ajog.2011.06.067","article-title":"Gynecologic conditions in participants in the NSABP breast cancer prevention study of tamoxifen and raloxifene (STAR)","volume":"205","author":"Runowicz","year":"2011","journal-title":"Am J Obstet Gynecol"},{"key":"2026060902504118600_djaf250-B14","doi-asserted-by":"publisher","first-page":"4201","DOI":"10.1200\/JCO.2006.09.4318","article-title":"Randomized dose-ranging trial of tamoxifen at low doses in hormone replacement therapy users","volume":"25","author":"Decensi","year":"2007","journal-title":"J Clin Oncol"},{"key":"2026060902504118600_djaf250-B15","doi-asserted-by":"publisher","first-page":"2753","DOI":"10.1093\/annonc\/mdt244","article-title":"A phase-III prevention trial of low-dose tamoxifen in postmenopausal hormone replacement therapy users: the HOT study","volume":"24","author":"DeCensi","year":"2013","journal-title":"Ann Oncol"},{"key":"2026060902504118600_djaf250-B16","doi-asserted-by":"publisher","first-page":"3749","DOI":"10.1200\/JCO.2008.19.3797","article-title":"Randomized double-blind 2 x 2 trial of low-dose tamoxifen and fenretinide for breast cancer prevention in high-risk premenopausal women","volume":"27","author":"Decensi","year":"2009","journal-title":"J Clin Oncol"},{"key":"2026060902504118600_djaf250-B17","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1093\/jnci\/95.4.302","article-title":"Effects of tamoxifen on benign breast disease in women at high risk for breast cancer","volume":"95","author":"Tan-Chiu","year":"2003","journal-title":"J Natl Cancer Inst"},{"key":"2026060902504118600_djaf250-B18","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1158\/1940-6207.CAPR-24-0483","article-title":"Selecting the right dose to move breast cancer prevention forward","volume":"17","author":"King","year":"2024","journal-title":"Cancer Prev Res (Phila)"}],"container-title":["JNCI: Journal of the National Cancer Institute"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jnci\/advance-article-pdf\/doi\/10.1093\/jnci\/djaf250\/64163097\/djaf250.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jnci\/article-pdf\/118\/6\/1115\/64163097\/djaf250.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jnci\/article-pdf\/118\/6\/1115\/64163097\/djaf250.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T06:50:50Z","timestamp":1780987850000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jnci\/article\/118\/6\/1115\/8244295"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,29]]},"references-count":18,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,8,29]]},"published-print":{"date-parts":[[2026,6,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jnci\/djaf250","relation":{},"ISSN":["0027-8874","1460-2105"],"issn-type":[{"value":"0027-8874","type":"print"},{"value":"1460-2105","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,6]]},"published":{"date-parts":[[2025,8,29]]}}}