Abstract 26: Intraductal procedure with refined ethanol-containing ablative solution for primary prevention of breast cancer
Authors: Zaluzec Erin Kay , Kenyon Elizabeth , Volk Maximilian , Jackson Brooke L. , Hix Jeremy , Chakravarty Shatadru , Shapiro Erik , Moore Anna , Sempere Lorenzo F. 
Published: September 2020

Abstract
Breast cancer (BC) is the second leading cause of cancer-related deaths in women. One in every eight women will develop BC during her lifetime. For moderate and low risk women, there are few options available for prevention. For high-risk patients, prophylactic mastectomy is the most effective intervention for primary prevention of BC. Prophylactic mastectomy consists of the complete removal of mammary epithelial cells, from which the majority of BC arises, and the surrounding tissue which can have great physical, emotional, and psychological tolls on the individual. Therefore, fewer than 30% of high-risk individuals choose to undergo this aggressive procedure as their primary intervention. We seek to develop an alternative, minimally invasive procedure that intraductally delivers a cell-killing solution throughout the ductal tree to ablate the mammary epithelial cells before they become malignant. Existing methods such as ductography for clinical diagnostic imaging support the technical feasibility of this approach. We recently published a proof-of-concept study with ethanol as an intraductal (ID) ablative solution in non-transgenic FVB mice and in a C(3)1-tag FVB BC model. Ethanol is a safe compound with multiple clinical applications as an ablative and sclerosing agent. ID injections of 70% ethanol showed maximal and most consistent epithelial cell ablation than other tested concentrations with limited and tolerable collateral damage in the surrounding tissue. ID injections of 70% ethanol in cancer prone C(3)1-tag mice significantly delayed tumor formation and reduced tumor incidence. We followed up 10 ethanol-injected FVB animals until their natural death (median survival &gt; 630 days), with no long-term adverse effects observed. Here, we tested different formulations to further minimize collateral tissue damage of 70% ethanol. We added ethyl cellulose, a gelling agent used to limit diffusion of ethanol in clinical treatments of venous malformation and pre-clinical liver cancer, to the 70% ethanol solution. Non-transgenic FVB mice and Sprague-Dawley rats ID injected with this refined ablative formulation achieved the same ablative rates as 70% ethanol solution but further minimized collateral damage to surrounding vasculature and adipose tissue. Introduction of tantalum oxide nanocrystals as high-resolution radiographic contrast agent into the ablative solution enabled unprecedented in vivo visualization of ductal tree filling and monitoring of 70% ethanol ablative effects in rodent models. Future studies will test the efficacy of this refined formulation to prevent BC in genetically engineered mouse models and chemical-induced rat models. The pre-clinical validation of this ID ablative procedure in aforementioned cancer-prone rodent models will further support the translatability of this approach to first-in-human clinical trials for high-risk individuals.
Citation Format: Erin Kay Zaluzec, Elizabeth Kenyon, Maximilian Volk, Brooke L. Jackson, Jeremy Hix, Shatadru Chakravarty, Erik Shapiro, Anna Moore, Lorenzo F. Sempere. Intraductal procedure with refined ethanol-containing ablative solution for primary prevention of breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 26.