Abstract 3389: Intraductal ablative procedure for local preventive intervention in rat models of breast cancer
Authors: Zaluzec Erin , Ashry Mohamed , Phelps Elizabeth G. , Kempinska Katarzyna , Kenyon Elizabeth , Kenny Legend , Volk Max , Powell Katherine , Hix Jeremy ML , Mallett Christiane , Kiupel Matti , Shapiro Erik M. , Sempere Lorenzo F. 
Published: March 2024

Abstract
There are limited options for primary prevention of breast carcinoma (BC). Prophylactic mastectomy and systemic hormonal therapy are only recommended for high-risk individuals. Prophylactic mastectomy is a drastic surgery that removes the entire breast, including the epithelial cell-lined ductal trees where BC arises but also uninvolved stroma. Even with a 90% risk reduction, many women are deterred from prophylactic mastectomy due to its associated risk of infection, lymphedema, painful recovery time, and mental health toll. Hormonal therapies, tamoxifen and raloxifene, reduce BC risk by upwards of 50% but also increase the risk of uterine cancer and stroke. Thus, new interventions to reduce the risk of BC and minimize deterrents are necessary. Intraductal (ID) injection is a minimally invasive procedure that avoids systemic toxicity by cannulating a needle directly into the ductal tree opening to directly administer a solution to the epithelial cells. We previously reported that ID infusion of 70% ethanol (EtOH) as a cell-killing solution prevents tumor formation in an aggressive genetically engineered mouse model of BC with minimum collateral tissue damage. Here, we investigated the therapeutic efficacy of EtOH-based ablative solutions in a Methyl-N-Nitrosourea (MNU) chemically induced rat model of BC to assess scalability of this procedure towards clinical trials. Two weeks after tumor induction, rats received ID infusions of a solution containing 70% EtOH to ablate epithelial cells, ethyl cellulose (EC) to minimize collateral tissue damage, and/or Tantalum Oxide (TaOx) to visualize infused ductal trees via micro-CT imaging. EtOH-infused glands had the longest tumor latency (273 days vs 97 days in control group, p &lt; 0.0001). No statistically significant differences were noted in epithelial ablation or collateral tissue damage between treatment groups receiving ID injections of 70% EtOH with varying concentrations of EC, but there was a trend to lower collateral damage with EC-containing solutions. Local clearance of TaOx in infused mammary glands enabled post-procedure MR imaging surveillance after 15 d of ID procedure. This preclinical study demonstrates that ID injection of a refined solution containing 70% EtOH and TaOx is an efficacious and scalable procedure for primary prevention of BC.
Citation Format: Erin Zaluzec, Mohamed Ashry, Elizabeth G. Phelps, Katarzyna Kempinska, Elizabeth Kenyon, Legend Kenny, Max Volk, Katherine Powell, Jeremy ML Hix, Christiane Mallett, Matti Kiupel, Erik M. Shapiro, Lorenzo F. Sempere. Intraductal ablative procedure for local preventive intervention in rat models of breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3389.