Abstract PS8-33: Image-guided intraductal ablation with refined ethanol solution for primary prevention of breast cancer
Authors: Sempere Lorenzo , Kenyon Elizabeth , Chakravarty Shatadru , Volk Maximilian , Hix Jeremy ML , Zaluzec Erin , Kiupel Matti , Shapiro Erik 
Published: February 2021

Abstract
Breast cancer (BC) is the most prevalent cancer and the second-leading cause of cancer-related death for women in the USA. For moderate-risk and, especially, low-risk women with a 1-in-8 lifelong chance of developing BC, there are very few options available to reduce their risk. For high-risk women, prophylactic mastectomy is currently the most effective procedure for preventing BC. Prophylactic mastectomy completely removes the mammary epithelial cells from which BC arises along with surrounding tissue. This aggressive surgical procedure affects women physically, emotionally, psychologically, aesthetically, and socially. Therefore, there is a need to develop new strategies for primary prevention that focus on high-risk women, but that, at the same time, could be also applied to moderate- and low-risk women. Our overall hypothesis is that the local killing of mammary epithelial cells will be as effective as prophylactic mastectomy in preventing BC, but with minimal side effects. Preclinical and clinical research studies as well as clinical application of intraductal (ID) procedures such as ductography for diagnostic imaging strongly support the translational feasibility of our approach. EtOH has been long used clinically as an ablative or sclerosing agent for local treatment. We recently showed that ID injection of a 70% EtOH solution is effective at locally ablating mammary epithelial cells with limited collateral tissue damage and at preventing tumor formation in an aggressive and multifocal mouse model of BC. We also recently developed tantalum oxide (TaOx) nanoparticles as a larger and higher radiopaque contrast agent with a much lower rate of outward diffusion than iodine-based contrast agents used in clinical ductography. Here, we investigated a refined EtOH formulation that consists of the addition of: i) TaOx nanoparticles as a high-resolution contrast agent to monitor in vivo filling of ductal trees and ablative effects of EtOH by computed tomography imaging; and ii) ethyl-cellulose (EC) as gelling agent to further minimize collateral tissue damage. This TaOx-based imaging approach provided unprecedented resolution to visualize individual ducts and branches of the ductal tree network after initial ID injection and architectural changes over 7 d due to local retention of TaOx nanoparticles in both PBS and EtOH solutions. EC is used clinically to improve delivery of EtOH and to limit EtOH diffusion from the intended target area in the treatment of venous malformations. ID injection of 70% EtOH/3% EC in nontransgenic mice and rats achieved the same epithelial ablation rate as 70% EtOH alone, while significantly minimizing collateral tissue damage. These results demonstrate the compatibility, safety, and stability of this refined EtOH formulation and support its further investigation in cancer-prone rodent and larger animal models as an innovative primary intervention strategy for BC prevention.
Citation Format: Lorenzo Sempere, Elizabeth Kenyon, Shatadru Chakravarty, Maximilian Volk, Jeremy ML Hix, Erin Zaluzec, Matti Kiupel, Erik Shapiro. Image-guided intraductal ablation with refined ethanol solution for primary prevention of breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-33.