Grants We Funded

Abstract
Expander-based post-mastectomy reconstruction is often precluded or delayed in breast cancer patients who require radiation (XRT) as a component of their breast cancer treatment. The deleterious consequences of XRT including destruction of skin and soft tissue, blood vessel obliteration, and aesthetic compromise, results in an unacceptably high incidence of complications in the setting of expander-based reconstruction. Amifostine (AMF) pre-treatment has been shown to protect bone and surrounding soft tissues from radiation damage during repair and regeneration in a small animal model. However, investigations regarding the radio-protective benefits of amifostine in a breast expansion model have been limited. The principal hypothesis to be tested is that radiation results in detrimental alterations in soft tissue collagen structure which ultimately lead to changes in tissue elasticity and strength. We further posit that the devastating effects of XRT-induced injury can be prevented utilizing the targeted pharmaco-therapeutic agent AMF.
In our study we will use Sprague Dawley rats (n=48) divided into three groups: Group 1 (controls) will undergo expander placement with subsequent expansion after a post-operative recovery period. Group 2 animals will undergo expander placement with XRT. Group 3 animals will undergo expansion with AMF therapy and XRT. For rats undergoing XRT, a human equivalent post-mastectomy radiation dose is administered with AMF given 45 minutes prior to XRT. Measured outcome metrics will include immunohistochemistry, scanning probe microscopy, and soft tissue tensile testing. By utilizing these parameters we will be investigating the cellular and structural effects of the damage of XRT with the corresponding mitigation of these metrics with AMF.
The long-term objective of our work is to determine the effect of radiotherapy induced devastation on the skin and soft tissue in a clinically relevant expander based reconstruction model and subsequently innovate radio-protective therapies designed to mitigate the pernicious effects of XRT. Successfully offering radio-protection would generate a significant impact on the availability of breast reconstruction for many women while decreasing the complication rates, cost, and resources required.

Biography
Dr. Alicia Snider, MD is a current research fellow in the Plastic Surgery Section at the University of Michigan, with a dedicated two year full-time commitment to research. Her research interest involves investigating the deleterious effects of radiation on bone and soft tissues. Her current focus is the study of the cytoprotective agent amifostine and its use in alleviating the negative consequences of radiation in a murine breast expansion model. She is completing her post-doctoral research between her third and fourth years of clinical training in general surgery residency at Palmetto Health Richland Hospital, University of South Carolina School of Medicine. Upon completion of her general surgery residency she intends to pursue further training in plastic and reconstructive surgery. She will be responsible for the design, planning, and execution of the project outlined in the proposal and will work closely with her mentor, Dr. Steven Buchman to accomplish these goals.