Abstract PO5-19-12: Innovative Trial Design: ARTIDIS Nanomechanical Generated Measurements for Early Breast Lesions (ANGEL) - Multicentre Study

Abstract Background: The diagnosis of breast cancer based on histopathology of core needle biopsies and the delineation into breast cancer subtypes to drive clinical treatment decisions can be time consuming and cause patient (and clinician) anxiety. Alternative, near patient, approaches to conventional diagnostic pathways would be desirable to drive diagnostic and therapeutic planning. This study harnesses the novel concept of evaluating diagnostic cores for nanomechanical features at the time of core biopsy. Clinical manifestations of disease are often accompanied by biomechanical alterations at sub-/cellular, extracellular, tissue and organ level. Mechanical properties of cancer cells and their microenvironment play a critical role in cancer invasion, progression, and immune cell infiltration. Ultrastructural (sub-) cellular alterations (nanoscale level), including the remodulation and alteration of cellular cytoskeleton dynamics, contribute to altered mechanical state of cancer cells, and lead to increased deformability and motility of soft cancer cells to overcome stromal barrier, and spread into the adjacent tissues and distant sites in the body. This results in a direct mechanistic correlation between nanomechanical properties and clinical outcome in cancer tissues. The ARTIDIS Nanomechanical Generated measurements for Early Lesions (ANGEL) Study will prospectively evaluate the efficacy of the ARTIDIS system as an aid to diagnosis, as well as subtyping breast cancer and predicting clinical outcomes based on tissue nanomechanics, particularly in the context of neoadjuvant therapy (NAT). Methods: The study seeks to validate the predictive power of the nanomechanical signature, a unique tissue biomarker reflecting the tissue phenotype, by comparing it to standard histological assessment. A projected cohort of 2,705 patients will be enrolled, from diverse ethnic and socioeconomic backgrounds, with benign or malignant breast conditions undergoing diagnostic core biopsy. A single core biopsy (gauge agnostic) is placed in a cassette and subjected to thousands of mechanical measurements at the “nano” scale over a period of 1-3 hours. The ARTIDIS technology builds upon the Atomic Force Microscopy platform to non-disruptively detect up to 17 different nanomechanical parameters in soft tissues with a subcellular resolution. The same core biopsy can then undergo fixation and conventional histopathological analyses for comparison with the final pathology. The primary aim is to confirm the potential of the ARTIDIS system in diagnosis (benign vs malignant) and secondarily address whether the nanomechanical signature can differentiate subtypes of breast cancer, associate with clinical outcome, and guide treatment decisions. Particularly, we will investigate ARTIDIS potential as a predictor of treatment response for patients receiving NAT. Results: The multicenter ANGEL study is a prospective investigation that builds upon previous clinical data from the NANO study at the University Hospital Basel (Switzerland) and is designed to demonstrate the power of using a nanomechanical signature to evaluate breast biopsies within a routine clinical setting in a multicenter setting. The data will be used to develop ARTIDIS as an aid to diagnosis, as well as NEO Match test applications to predict and guide response to NAT. Conclusion: This study presents the first of its kind as a direct prospective, multi-center based clinical translation of the Physics of Cancer findings into clinical settings. This innovative trial design allows the prospective development of ARTIDIS as an aid to diagnosis and NAT outcome prediction and therapy guidance applications. Citation Format: Karla Sepulveda, Ashley Roark, Sagar Dhamne, Chandandeep Nagi, Ivan Marin, Iqbal Tabish, Susanne G. Hilsenbeck Hilsenbeck, Sara Nizzero, Mariam Gachechiladze, Tobias A Appenzeller, Marko Loparic, Marija Plodinec, Alastair Thompson. Innovative Trial Design: ARTIDIS Nanomechanical Generated Measurements for Early Breast Lesions (ANGEL) - Multicentre Study abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-19-12.