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Cited by 25Lymphatic System and DiseasesBreast Cancer Treatment StudiesChemotherapy-related skin toxicity

Treatment of Breast Cancer-Related Lymphedema With Topical Tacrolimus: A Prospective, Open-Label, Single-Arm, Phase II Pilot Trial

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Gulmark Hansen, Frederik C., Jørgensen, Mads Gustaf, Sørensen, Jens Ahm·2023·Journal of Breast Cancer
DOI 10.4048/jbc.2023.26.e2PMC PMC9981991
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Abstract

Purpose: Breast cancer-related lymphedema (BCRL) is a chronic, progressive side effect of breast cancer treatment, occurring in one-third of patients treated with axillary lymph node dissection and nodal radiotherapy.Cluster of differentiation 4-positive (CD4 + ) cells plays a key role in BCRL by facilitating inflammation and inhibiting lymphangiogenesis.Tacrolimus is an anti-inflammatory and immunosuppressive macrolide that targets CD4 + cells.Treatment of lymphedema with topical tacrolimus has revealed promising results in preclinical trials.This clinical trial was aimed at evaluating the feasibility, safety, and effect of tacrolimus in women with stage I or II BCRL, according to the International Society of Lymphology. Methods:We conducted this open-label, single-arm, phase II pilot trial from September 2020 to April 2021.Eighteen women with BCRL stage I or II BCRL were treated with topical tacrolimus for 6 months and followed up at 3 and 6 months.The primary outcome was arm volume, and secondary outcomes were the lymphedema index (L-Dex), health-related quality of life (HRQoL), lymph flow and function, and safety and feasibility of the trial design.Results: The mean lymphedema arm volume and L-Dex reduced significantly by 130.44 ± 210.13 mL (p < 0.05; relative reduction: 3.6%) and 3.54 ± 4.98 (p < 0.05), respectively, and health-related quality of life scores was improved significantly (p < 0.05).According to the MD Anderson scale, in terms of lymph flow and function, three patients (16.7%) showed improvement, while none showed worsening.Lymph flow or function showed no change according to the Arm Dermal Backflow scale.Conclusion: In this trial, treatment with tacrolimus was safe and feasible in women with stage I or II BCRL.Tacrolimus alleviated BCRL in terms of improved arm volume, L-Dex, and HRQoL.Assessments of lymph flow and function were positive, although inconclusive.Larger randomized controlled trials are required to verify these findings.

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  • CD4+ T cell inhibition with tacrolimus was effective in the mouse tail wound model, and a phase 2 clinical trial of topical tacrolimus resulted in limb volume reduction in breast cancer lymphedema patients.

    “CD4+ T cell inhibition with tacrolimus, a calcineurin inhibitor, was effective in the mouse tail wound model (149), and a phase 2 clinical trial of topical tacrolimus application resulted in limb volume reduction in breast cancer lymphedema patients (150).”

    From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [150]

  • Lymphatic function as assessed by indocyanine green was not significantly improved by tacrolimus despite limb volume reduction.

    “However, lymphatic function as assessed by indocyanine green was not significantly improved by tacrolimus despite limb volume reduction in that study (150).”

    From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [150]

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Cited by

Sorted by citations

Authors
Gulmark Hansen, F. C., Jørgensen, M. G., & Sørensen, J. A.
Affiliations
  • Research Unit for Plastic Surgery, Odense University Hospital, Odense, Denmark.
  • University of Southern Denmark (DK)
ORCID
Venue
Journal of Breast Cancer
Publisher
XMLink
Published
2023
Volume
26
Issue
1
Pages
46
ISSN
  • 1598-3641 (ISSN-L)
  • 1738-6756
  • 2092-9900
DOI
10.4048/jbc.2023.26.e2
PMC
PMC9981991
OpenAlex
W4319031847
Cited by
25
References
5
Citations by year
2026: 6 · 2025: 9 · 2024: 6 · 2023: 4
FWCI
3.05
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Breast Cancer (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion, cc-by-nc)
Funders
  • Kræftens Bekæmpelse (R288-A16159)
  • Dagmar Marshalls Fond (1022-2993-01)
Topics
  • Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
  • Health Sciences › Medicine › Dermatology › Chemotherapy-related skin toxicity
Keywords
breast cancer-related lymphedema, topical tacrolimus, CD4+ T cells, lymphangiogenesis, arm volume, health-related quality of life, lymph flow, axillary lymph node dissection, radiotherapy complications, immunosuppressive therapy

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