Topical Deferoxamine Alleviates Skin Injury and Normalizes Atomic Force Microscopy Patterns Following Radiation in a Murine Breast Reconstruction Model

Alicia E. Snider, Jeremy V. Lynn, Kevin M. Urlaub, Alexis Donneys, Yekaterina Polyatskaya, Noah S. Nelson, Russell E. Ettinger, Geoffrey C. Gurtner, Mark M. Banaszak Holl, Steven R. Buchman

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background Breast cancer is most commonly managed with a combination of tumor ablation, radiation, and/or chemotherapy. Despite the oncologic benefit of these treatments, the detrimental effect of radiation on surrounding tissue challenges the attainment of ideal breast reconstruction outcomes. The purpose of this study was to determine the ability of topical deferoxamine (DFO) to reduce cutaneous ulceration and collagen disorganization following radiotherapy in a murine model of expander-based breast reconstruction. Methods Female Sprague-Dawley rats (n = 15) were divided into 3 groups: control (expander), XRT (expander + radiation), and DFO (expander + radiation + deferoxamine [DFO]). Expanders were placed in a submusculocutaneous plane in the right upper back and ultimately filled to 15 mL. Radiation was administered via a fractionated dose of 28 Gy. Deferoxamine was delivered topically for 10 days following radiation. After a 20-day recovery period, skin ulceration and dermal type I collagen organization were analyzed. Results Compared with control, the XRT group demonstrated a significant increase in skin ulceration (3.7% vs 43.3%, P = 0.00) and collagen fibril disorganization (26.3% vs 81.8%, P = 0.00). Compared with the XRT group, treatment with topical DFO resulted in a significant reduction in ulceration (43.3% vs 7.0%, P = 0.00) and fibril disorganization (81.8% vs 15.3%, P = 0.00). There were no statistical differences between the control and DFO groups in skin ulceration or collagen disorganization. Conclusions This study suggests topical DFO is capable of reducing skin ulceration and type I collagen fibril disorganization following radiotherapy. This novel application of DFO has potential to enhance expander-based breast reconstruction outcomes and improve quality of life for women suffering the devastating effects of breast cancer.

Original languageEnglish
Pages (from-to)604-608
Number of pages5
JournalAnnals of Plastic Surgery
Volume81
Issue number5
DOIs
Publication statusPublished - 1 Nov 2018
Externally publishedYes

Keywords

  • breast expander
  • cancer
  • fibrosis
  • skin ulceration
  • type I collagen

Cite this

Snider, Alicia E. ; Lynn, Jeremy V. ; Urlaub, Kevin M. ; Donneys, Alexis ; Polyatskaya, Yekaterina ; Nelson, Noah S. ; Ettinger, Russell E. ; Gurtner, Geoffrey C. ; Banaszak Holl, Mark M. ; Buchman, Steven R. / Topical Deferoxamine Alleviates Skin Injury and Normalizes Atomic Force Microscopy Patterns Following Radiation in a Murine Breast Reconstruction Model. In: Annals of Plastic Surgery. 2018 ; Vol. 81, No. 5. pp. 604-608.
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title = "Topical Deferoxamine Alleviates Skin Injury and Normalizes Atomic Force Microscopy Patterns Following Radiation in a Murine Breast Reconstruction Model",
abstract = "Background Breast cancer is most commonly managed with a combination of tumor ablation, radiation, and/or chemotherapy. Despite the oncologic benefit of these treatments, the detrimental effect of radiation on surrounding tissue challenges the attainment of ideal breast reconstruction outcomes. The purpose of this study was to determine the ability of topical deferoxamine (DFO) to reduce cutaneous ulceration and collagen disorganization following radiotherapy in a murine model of expander-based breast reconstruction. Methods Female Sprague-Dawley rats (n = 15) were divided into 3 groups: control (expander), XRT (expander + radiation), and DFO (expander + radiation + deferoxamine [DFO]). Expanders were placed in a submusculocutaneous plane in the right upper back and ultimately filled to 15 mL. Radiation was administered via a fractionated dose of 28 Gy. Deferoxamine was delivered topically for 10 days following radiation. After a 20-day recovery period, skin ulceration and dermal type I collagen organization were analyzed. Results Compared with control, the XRT group demonstrated a significant increase in skin ulceration (3.7{\%} vs 43.3{\%}, P = 0.00) and collagen fibril disorganization (26.3{\%} vs 81.8{\%}, P = 0.00). Compared with the XRT group, treatment with topical DFO resulted in a significant reduction in ulceration (43.3{\%} vs 7.0{\%}, P = 0.00) and fibril disorganization (81.8{\%} vs 15.3{\%}, P = 0.00). There were no statistical differences between the control and DFO groups in skin ulceration or collagen disorganization. Conclusions This study suggests topical DFO is capable of reducing skin ulceration and type I collagen fibril disorganization following radiotherapy. This novel application of DFO has potential to enhance expander-based breast reconstruction outcomes and improve quality of life for women suffering the devastating effects of breast cancer.",
keywords = "breast expander, cancer, fibrosis, skin ulceration, type I collagen",
author = "Snider, {Alicia E.} and Lynn, {Jeremy V.} and Urlaub, {Kevin M.} and Alexis Donneys and Yekaterina Polyatskaya and Nelson, {Noah S.} and Ettinger, {Russell E.} and Gurtner, {Geoffrey C.} and {Banaszak Holl}, {Mark M.} and Buchman, {Steven R.}",
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Topical Deferoxamine Alleviates Skin Injury and Normalizes Atomic Force Microscopy Patterns Following Radiation in a Murine Breast Reconstruction Model. / Snider, Alicia E.; Lynn, Jeremy V.; Urlaub, Kevin M.; Donneys, Alexis; Polyatskaya, Yekaterina; Nelson, Noah S.; Ettinger, Russell E.; Gurtner, Geoffrey C.; Banaszak Holl, Mark M.; Buchman, Steven R.

In: Annals of Plastic Surgery, Vol. 81, No. 5, 01.11.2018, p. 604-608.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Topical Deferoxamine Alleviates Skin Injury and Normalizes Atomic Force Microscopy Patterns Following Radiation in a Murine Breast Reconstruction Model

AU - Snider, Alicia E.

AU - Lynn, Jeremy V.

AU - Urlaub, Kevin M.

AU - Donneys, Alexis

AU - Polyatskaya, Yekaterina

AU - Nelson, Noah S.

AU - Ettinger, Russell E.

AU - Gurtner, Geoffrey C.

AU - Banaszak Holl, Mark M.

AU - Buchman, Steven R.

PY - 2018/11/1

Y1 - 2018/11/1

N2 - Background Breast cancer is most commonly managed with a combination of tumor ablation, radiation, and/or chemotherapy. Despite the oncologic benefit of these treatments, the detrimental effect of radiation on surrounding tissue challenges the attainment of ideal breast reconstruction outcomes. The purpose of this study was to determine the ability of topical deferoxamine (DFO) to reduce cutaneous ulceration and collagen disorganization following radiotherapy in a murine model of expander-based breast reconstruction. Methods Female Sprague-Dawley rats (n = 15) were divided into 3 groups: control (expander), XRT (expander + radiation), and DFO (expander + radiation + deferoxamine [DFO]). Expanders were placed in a submusculocutaneous plane in the right upper back and ultimately filled to 15 mL. Radiation was administered via a fractionated dose of 28 Gy. Deferoxamine was delivered topically for 10 days following radiation. After a 20-day recovery period, skin ulceration and dermal type I collagen organization were analyzed. Results Compared with control, the XRT group demonstrated a significant increase in skin ulceration (3.7% vs 43.3%, P = 0.00) and collagen fibril disorganization (26.3% vs 81.8%, P = 0.00). Compared with the XRT group, treatment with topical DFO resulted in a significant reduction in ulceration (43.3% vs 7.0%, P = 0.00) and fibril disorganization (81.8% vs 15.3%, P = 0.00). There were no statistical differences between the control and DFO groups in skin ulceration or collagen disorganization. Conclusions This study suggests topical DFO is capable of reducing skin ulceration and type I collagen fibril disorganization following radiotherapy. This novel application of DFO has potential to enhance expander-based breast reconstruction outcomes and improve quality of life for women suffering the devastating effects of breast cancer.

AB - Background Breast cancer is most commonly managed with a combination of tumor ablation, radiation, and/or chemotherapy. Despite the oncologic benefit of these treatments, the detrimental effect of radiation on surrounding tissue challenges the attainment of ideal breast reconstruction outcomes. The purpose of this study was to determine the ability of topical deferoxamine (DFO) to reduce cutaneous ulceration and collagen disorganization following radiotherapy in a murine model of expander-based breast reconstruction. Methods Female Sprague-Dawley rats (n = 15) were divided into 3 groups: control (expander), XRT (expander + radiation), and DFO (expander + radiation + deferoxamine [DFO]). Expanders were placed in a submusculocutaneous plane in the right upper back and ultimately filled to 15 mL. Radiation was administered via a fractionated dose of 28 Gy. Deferoxamine was delivered topically for 10 days following radiation. After a 20-day recovery period, skin ulceration and dermal type I collagen organization were analyzed. Results Compared with control, the XRT group demonstrated a significant increase in skin ulceration (3.7% vs 43.3%, P = 0.00) and collagen fibril disorganization (26.3% vs 81.8%, P = 0.00). Compared with the XRT group, treatment with topical DFO resulted in a significant reduction in ulceration (43.3% vs 7.0%, P = 0.00) and fibril disorganization (81.8% vs 15.3%, P = 0.00). There were no statistical differences between the control and DFO groups in skin ulceration or collagen disorganization. Conclusions This study suggests topical DFO is capable of reducing skin ulceration and type I collagen fibril disorganization following radiotherapy. This novel application of DFO has potential to enhance expander-based breast reconstruction outcomes and improve quality of life for women suffering the devastating effects of breast cancer.

KW - breast expander

KW - cancer

KW - fibrosis

KW - skin ulceration

KW - type I collagen

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U2 - 10.1097/SAP.0000000000001592

DO - 10.1097/SAP.0000000000001592

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