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Amifostine: A Safe and Effective Prophylactic Radioprotectant in Irradiated Breast Reconstruction
Alexandra O. Luby, MS; Jeremy V. Lynn, BS; Lauren Buchman; Noah S. Nelson, MS; Alexis Donneys, MD; Mark S. Cohen, MD; Steven R. Buchman, MD
University of Michigan
2019-02-12
Presenter: Alexandra O. Luby, MS
Affidavit:
Alex is a medical student working in my laboratory. She is not a resident, so she does not have a program director. I am the principal investigator of this project. I certify that this submission represents Alex's original work, as she has performed majority of the work on this project and she has my approval to submit this work and present it.
Director Name: Steven R. Buchman
Author Category: Medical Student
Presentation Category: Basic Science Research
Abstract Category: Breast (Aesthetic and Recon.)
Background: Radiation therapy (XRT) is a highly effective breast cancer treatment; however, it damages surrounding tissues and vasculature, leaving patients with devastating side-effects and delayed or compromised breast reconstruction. Thus, effective, yet safe methods of radiation injury prophylaxis are needed. Amifostine (AMF) is a FDA-approved radio-protectant, however, concerns about AMF protecting cancer from XRT persist. While the safety of AMF in head and neck cancer is well studied, it remains to be investigated in breast cancer. The purpose of this study was to evaluate the oncologic safety of Amifostine and determine its effect on triple-negative breast cancer in the setting of XRT.
Methods: Two ER-/PR-/Her2- breast cancer cell lines (MDA-MB-231,MDA-MB-468) and one healthy cell line (Female Fibroblasts(FF)), were investigated. Cells were treated with 0.25 mM WR-1065, the active metabolite of AMF, 20 minutes before XRT at 0Gy, 10Gy, or 20Gy. Live and dead cells were quantified after 48h; percent cell death was calculated.
Results: WR-1065 treatment significantly reduced healthy FF death after XRT compared to untreated controls. Both MDA-MB-468 and MDA-MB-231 cells exhibited radio-sensitivity with substantial cell death at 10 and 20 Gy. Cancer cells retained their radio-sensitivity despite pretreatment with WR-1065, as they achieved the same degree of cell death as controls.
Conclusions: Amifostine does not protect triple-negative breast cancer cells from XRT. This study demonstrated its proficiency to selectively protect healthy cells from XRT, while cancer cells remained radiosensitive. These results support the oncologic safety of Amifostine, and identify it as a highly effective radio-protectant in breast cancer.
