Abstract
Breast cancer is the second leading cancer-related cause of death in women. While there are few proactive interventions for average-risk women, prophylactic mastectomy is the most effective, risk-reducing intervention for high-risk women. However, prophylactic mastectomy is an invasive procedure that removes all mammary epithelial cells along with the surrounding stroma, fat tissue, and/or musculature. Our overall research goal is to develop a non-invasive intraductal (ID) delivery procedure that locally kills the mammary epithelial cells by filling the entire ductal tree with an ablative solution. We previously demonstrated that ID delivery of ethanol as an ablative solution is effective in rodent models (mice and rats). This protocol presents an ID delivery of 10-70% ethanol solution containing iohexol (90-300 mg/mL) as an X-ray contrast agent into the multi-ductal tree system of the rabbit mammary gland. The mammary gland of a rabbit (Oryctolagus cuniculus) with a multi-duct system is more alike to the human breast than those of other large animals (e.g., cows, sheep). This rabbit protocol addresses technical challenges of scalability, real-time imaging, and ID delivery into a multi-ductal tree system in a large-animal intermediate model. This protocol establishes a fluoroscopy-guided multi-duct ID delivery with instruments, materials, and reagents that could be directly applied in the clinic. Tissue analysis enables optimizing the concentration of ethanol for maximal epithelial ablation and minimal collateral tissue damage as a starting point for future first-in-human evaluation of this ablative procedure for primary prevention of breast cancer.