Breast cancer (BC) is the leading cancer diagnosis accounting for 31% of all cancer cases for women in the United States. Equally as impactful, BC is also the second leading cause of cancer deaths among women. Despite the rise of BC diagnoses, the number of preventive interventions to mitigate the prevalence of cases is inadequate. Currently, only three BC prevention options are approved and implemented for women. Prophylactic mastectomy removes the entirety of the breast and reduces breast cancer risk by up to 90%. However, it’s a highly invasive procedure that takes many painful weeks to heal and can be emotionally exhausting. Tamoxifen and raloxifene are selective estrogen receptor modulators that have less risk reduction, only 50%. These drugs can increase the risk of stroke, endometrial cancer, and can induce postmenopausal symptoms early. Watchful waiting does not lower BC risk and relies on attentiveness, self-breast exams and annual checkups to detect tumor formation before it becomes cancerous. The harsh realities of the detrimental side effects outweigh the risk reduction benefits and deter most women from opting for these preventions. Consequently, only ‘high-risk’ women, those with a prevalent family history or BRCA1/2 mutations, even consider the choices. Therefore, it is imperative to investigate modern prevention methods with high-risk reduction while minimalizing side effects associated with current preventions because while treatments can save lives, prevention can save more. Unlike other organs, the breast, specifically the ductal tree, is accessible externally. The ductal tree is primarily composed of epithelial cells that line the lumen and are responsible for milk production and secretion but are the origin of most breast cancer cases. Intraductal (ID) injections are a unique approach solely for the breast that can directly target epithelial cells of the ductal tree through entry at the nipple. By utilizing ID injections to deliver an ablating agent, epithelial cells can be eradicated before they have a chance to become malignant with minimum invasion to the organ and no systemic processing. Ethanol is an inexpensive, readily available, ablating agent used for treatments such as unresectable liver tumors and breast pseudoaneurysms that can be repurposed for ID ablation as an effective prevention method. Therefore, the objective of this dissertation is to identify the impact of 70% ethanol ID ablation as a novel competitive approach for BC prevention that mitigates the shortcomings of existing preventive measures. Herein I demonstrated that ID ablation with 70% ethanol is an effective preventive for BC. A single injection can ablate a majority of epithelial cells within the ductal tree without inducing a cancerous effect. I investigated the minimum volume necessary for effective prevention while maintaining a high ablation rate. The translational ability of ID ablation was demonstrated by successful ablation and increased tumor latency from mouse to rat BC models. I explored the combination of ethanol and ethyl cellulose, a clinically used gelling agent, with the aim to mitigate ethanol dispersion which yielded no reduction in dispersion. The addition of tantalum oxide, a versatile X-ray contrast agent further supports the translational ability of ID ablation into clinics. However, further studies are needed to identify the impact on the local immune response and the exact mechanisms behind wound healing. The work is highly translational with tools readily available for repurposing and can have a direct impact on saving human lives.
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