{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:06:38Z","timestamp":1792785998816,"version":"4.5.0"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Atossa Therapeutics and was conducted entirely in Sweden by staff at Karolinska Institutet and at the three included hospitals","id":[{"id":"https:\/\/ror.org\/056d84691","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>(Z)-endoxifen is the tamoxifen metabolite that possesses the highest affinity to the estrogen receptor and is evolving as an alternative to tamoxifen. Mammographic breast density (MBD) change has been shown to be a proxy for tamoxifen therapy response. The objective was to measure the effect of 2 different doses of (Z)-endoxifen on MBD, safety, and side effects in healthy women.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Healthy premenopausal women included in the national Swedish screening program in Stockholm were invited to KARISMA Endoxifen, a proof of principle, dose determining, double-blinded, randomized, placebo-controlled trial. Women were randomly assigned to placebo or 1 or 2\u2009mg of (Z)-endoxifen daily for 6 months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In all, 240 women were randomly assigned. There was a significant relative change in MBD in both (Z)-endoxifen arms compared to placebo: \u221219.3% (95% confidence interval [CI] = \u22126.15% to \u221232.4%) in the 1\u2009mg arm and \u221226.5% (95% CI = \u221214.1% to \u221238.9%) in the 2\u2009mg arm. The number of participants discontinuing because of adverse events related to the investigational medicinal product was 4 (placebo), 5 (1\u2009mg), and 11 (2\u2009mg), respectively. Participants on 2\u2009mg of (Z)-endoxifen reported significantly higher scores of vasomotor symptoms, compared with placebo. No clinically significant changes in hematological safety tests or vital signs were noted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Both 1 and 2\u2009mg of (Z)-endoxifen significantly reduced MBD to a degree comparable to the established 20\u2009mg dose of tamoxifen. The 1\u2009mg dosage of (Z)-endoxifen indicated superior tolerability. Future studies are necessary to confirm impact on breast cancer incidence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov ID: NCT05068388.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jnci\/djag087","type":"journal-article","created":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T12:36:41Z","timestamp":1774096601000},"page":"1899-1906","source":"Crossref","is-referenced-by-count":0,"title":["Endoxifen for mammographic density reduction\u2014results from the KARISMA endoxifen trial"],"prefix":"10.1093","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5640-9126","authenticated-orcid":false,"given":"Per","family":"Hall","sequence":"first","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet , Stockholm,","place":["Sweden"]},{"name":"Department of Oncology, 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