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The Role of Deferoxamine in Irradiated Breast Reconstruction: A Study of Oncologic Safety

Lynn, Jeremy V. B.S.; Urlaub, Kevin M. B.S.; Ranganathan, Kavitha M.D.; Donneys, Alexis M.D., M.S.; Nelson, Noah S. M.P.H.; Subramanian, Chitra Ph.D., M.B.A.; Cohen, Mark S. M.D.; Buchman, Steven R. M.D.

Plastic and Reconstructive Surgery: June 2019 - Volume 143 - Issue 6 - p 1666-1676
doi: 10.1097/PRS.0000000000005647
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Background: Radiotherapy plays an essential role in the oncologic management of breast cancer. However, patients who undergo radiotherapy experience significantly more wound complications during the reconstructive process. Deferoxamine has immense potential to up-regulate angiogenesis and improve reconstructive outcomes. The purpose of this study was to determine the impact of deferoxamine on breast cancer cell proliferation in vitro, to delineate oncologic safety concerns regarding the use of deferoxamine as a regenerative therapeutic.

Methods: The dose-dependent effect of radiation and deferoxamine on two triple-negative breast cancer cell lines (MDA-MB-231 and MDA-MB-468) was determined by means of MTS (percentage cell viability) and tumorsphere (sphere number) analysis. Radiation therapy and deferoxamine were delivered both individually and in combination, and all experiments were completed in triplicate. Intracellular iron, nuclear factor-κB localization, and apoptosis/necrosis assays were performed to delineate mechanism. Analysis of variance statistical analysis was performed using SPSS (p < 0.05).

Results: For both cell lines, percentage viability and sphere number significantly decreased following exposure to 10 Gy of radiation. Surprisingly, the administration of 25 µM deferoxamine also significantly decreased each metric. The administration of deferoxamine (100 µM) in combination with radiation (10 Gy) resulted in significantly reduced percentage viability and sphere number compared with the administration of radiation alone. Deferoxamine treatment decreased intracellular iron, suppressed nuclear factor-κB activation, and induced apoptosis.

Conclusion: Radiation and deferoxamine significantly decrease breast cancer proliferation when delivered independently and in combination, suggesting deferoxamine may be safely used to facilitate improved reconstructive outcomes among triple-negative breast cancer survivors.

CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Ann Arbor, Mich.

From the Department of Surgery, Section of Plastic and Reconstructive Surgery, and the Department of Pharmacology, University of Michigan.

Received for publication April 23, 2018; accepted October 26, 2018.

Disclosure:The authors have no financial interest to declare in relation to the content of this article.

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Steven R. Buchman, M.D., University of Michigan, 1540 East Hospital Drive, Floor 4, Suite 4-730, Ann Arbor, Mich. 48104, sbuchman@med.umich.edu

Copyright © 2019 by the American Society of Plastic Surgeons