{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T14:20:58Z","timestamp":1779200458632,"version":"3.51.4"},"reference-count":33,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008363","name":"Danish Cancer Society","doi-asserted-by":"publisher","award":["R288-A16159"],"award-info":[{"award-number":["R288-A16159"]}],"id":[{"id":"10.13039\/100008363","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"publisher","award":["0095539"],"award-info":[{"award-number":["0095539"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Dagmar Marshall\u2019s Foundation","award":["1022-2993-01"],"award-info":[{"award-number":["1022-2993-01"]}]},{"name":"Fonden af 1870, Guldsmed A. L. Rasmussen\u2019s Memorial Fund"},{"name":"Grosserer A. V. Lykfeldt and Wife\u2019s Legacy"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Breast cancer-related lymphedema (BCRL) remains a challenging complication for breast cancer survivors. Currently, there are no effective pharmacological options available to address this condition. Emerging research highlights the critical role of inflammation, lymphatic dysfunction, and T-cell activity in the development of BCRL. Tacrolimus, a calcineurin inhibitor, has demonstrated promising results in preclinical studies for reducing inflammation, enhancing lymphatic function, and modulating T-cell activity\u2014key mechanisms implicated in BCRL pathogenesis. This study investigates whether topical tacrolimus ointment can reduce the incidence and severity of BCRL, providing a novel approach to mitigate this debilitating condition. Methods: A parallel, open-label non-randomized controlled multicenter clinical pilot trial was conducted from February 2020 to June 2022. Female participants undergoing axillary lymph node dissection (ALND) were recruited and divided into an intervention group (n = 22) receiving topical tacrolimus 0.1% ointment daily for 12 months and a control group (n = 39). Outcomes included lymphedema diagnosis (primary), arm volume, bioimpedance spectroscopy, quality of life (QOL) scores, and adverse events. Assessments were performed at baseline and at 3, 6, 9, and 12 months. Results: At 12 months, lymphedema was diagnosed in 3 of 18 patients (16.7%) in the intervention group and 4 of 37 patients (10.8%) in the control group (p &gt; 0.05). Mean increase in at-risk arm volume was 80.7 mL in the intervention group versus 116.1 mL in the control group (p &gt; 0.05). Disease-specific quality of life scores worsened in both groups, but scores returned to baseline at 12 months in the intervention group only. Adverse events were mild and manageable, with no serious events reported. Conclusions: While topical tacrolimus did not significantly reduce the incidence of lymphedema, exploratory patterns in symptom onset and quality-of-life measures indicate that further investigation in larger randomized trials may be warranted.<\/jats:p>","DOI":"10.3390\/cancers17233753","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T13:09:25Z","timestamp":1763989765000},"page":"3753","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exploratory Evaluation of Topical Tacrolimus for Prevention of Breast Cancer-Related Arm Lymphedema: A Multicenter Non-Randomized Pilot Study"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4588-8053","authenticated-orcid":false,"given":"Frederik","family":"Gulmark Hansen","sequence":"first","affiliation":[{"name":"Research Unit for Plastic Surgery, Odense University Hospital, 5000 Odense, Denmark"},{"name":"Institute of Clinical Research, University of Southern Denmark, 5000 Odense, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8755-3446","authenticated-orcid":false,"given":"Mads Gustaf","family":"J\u00f8rgensen","sequence":"additional","affiliation":[{"name":"Research Unit for Plastic Surgery, Odense University Hospital, 5000 Odense, Denmark"},{"name":"Institute of Clinical Research, University of Southern Denmark, 5000 Odense, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6800-4532","authenticated-orcid":false,"given":"Kim","family":"Gordon","sequence":"additional","affiliation":[{"name":"Department of Physio- and Occupational Therapy, Lillebelt Hospital, University Hospital of Southern Denmark, 7100 Vejle, Denmark"},{"name":"Department of Regional Health Research, University of Southern Denmark, 5000 Odense, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Kj\u00e6r","sequence":"additional","affiliation":[{"name":"Department of Plastic and Breast Surgery, Lillebaelt Hospital, University Hospital of Southern Denmark, 7100 Vejle, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lena Felicia","family":"Carstensen","sequence":"additional","affiliation":[{"name":"Department of Plastic and Breast Surgery, Lillebaelt Hospital, University Hospital of Southern Denmark, 7100 Vejle, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mette","family":"Tambour","sequence":"additional","affiliation":[{"name":"Department of Physiotherapy and Occupational Therapy, University Hospital of Southern Denmark, 6700 Esbjerg, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7655-688X","authenticated-orcid":false,"given":"Bibi","family":"Gram","sequence":"additional","affiliation":[{"name":"Department of Regional Health Research, University of Southern Denmark, 5000 Odense, Denmark"},{"name":"Research Unit of Endocrinology, Bariatrics, and Diabetes, University Hospital of Southern Denmark, 6700 Esbjerg, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7368-6133","authenticated-orcid":false,"given":"J\u00f8rn Bo","family":"Thomsen","sequence":"additional","affiliation":[{"name":"Research Unit for Plastic Surgery, Odense University Hospital, 5000 Odense, Denmark"},{"name":"Institute of Clinical Research, University of Southern Denmark, 5000 Odense, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4903-0094","authenticated-orcid":false,"given":"Jens Ahm","family":"S\u00f8rensen","sequence":"additional","affiliation":[{"name":"Research Unit for Plastic Surgery, Odense University Hospital, 5000 Odense, Denmark"},{"name":"Institute of Clinical Research, University of Southern Denmark, 5000 Odense, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1097\/01.sap.0000257149.42922.7e","article-title":"Lymphedema: A comprehensive review","volume":"59","author":"Warren","year":"2007","journal-title":"Ann. 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