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Tamoxifen is a standard treatment for receptor-positive breast cancer and is also aproved for primary prevention. We investigated the effect of tamoxifen and its main metabolites on the breast tissue collagen organisation as a proxy for stiffness and explored the relationship between mammographic density (MD) and collagen organisation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Material and methods<\/jats:title>\n                <jats:p>This sub-study of the double-blinded dose-determination trial, KARISMA, included 83 healthy women randomised to 6\u00a0months of 20, 10, 5, 2.5, and 1\u00a0mg of tamoxifen or placebo. Ultrasound-guided core-needle breast biopsies collected before and after treatment were evaluated for collagen organisation by polarised light microscopy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Tamoxifen reduced the amount of organised collagen and overall organisation, reflected by a shift from heavily crosslinked thick fibres to thinner, less crosslinked fibres. Collagen remodelling correlated with plasma concentrations of tamoxifen metabolites. MD change was not associated with changes in amount of organised collagen but was correlated with less crosslinking in premenopausal women.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>In this study of healthy women, tamoxifen decreased the overall organisation of fibrillar collagens, and consequently, the breast tissue stiffness. These stromal alterations may play a role in the well-established preventive and therapeutic effects of tamoxifen.<\/jats:p>\n                <jats:p><jats:italic>Trial registration<\/jats:italic> ClinicalTrials.gov ID: NCT03346200. Registered November 1st, 2017. Retrospectively registered.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13058-024-01919-1","type":"journal-article","created":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T07:45:27Z","timestamp":1732607127000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Low-dose tamoxifen treatment reduces collagen organisation indicative of tissue stiffness in the normal breast: results from the KARISMA randomised controlled trial"],"prefix":"10.1186","volume":"26","author":[{"given":"Sara","family":"G\u00f6ransson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Hern\u00e1ndez-Varas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattias","family":"Hammarstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxanna","family":"Hellgren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"B\u00e4cklund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"L\u00e5ng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann H.","family":"Rosendahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikael","family":"Eriksson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Signe","family":"Borgquist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Staffan","family":"Str\u00f6mblad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamila","family":"Czene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Hall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marike","family":"Gabrielson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,26]]},"reference":[{"key":"1919_CR1","doi-asserted-by":"publisher","first-page":"e100937","DOI":"10.1371\/journal.pone.0100937","volume":"9","author":"NF Boyd","year":"2014","unstructured":"Boyd NF, et al. 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