Abstract 3140: A prospective, double-blinded clinical study using atomic force microscopy for fast diagnosis and subtyping of low and high-risk breast cancers
Authors: Burian Rosemarie , Jizawi Ahmed , Zihlmann Gabriel , Appenzeller Tobias , Oertle Philipp , Raez Christian , Lim Roderick Y. , Forte Serafino , Dellas Sophie , Muenst Simone , Vlajnic Tatjana , Obermann Ellen , Ricci Maria , Grimm Kevin , Niedermann Ferdinand , Loparic Marko , Plodinec Marija 
Published: August 2019

Abstract
Mechanical properties and physical interactions of cells and their microenvironment that occur at nanometre scale play a critical role in cancer progression and metastatic dissemination (https://physics.cancer.gov). Nanomechanical profiling of breast tissue enables fast and precise cancer diagnosis. Detecting extreme viscoelastic (soft) cancer cells in biopsies provides a direct biomarker of cancer aggressiveness (Plodinec et. al., 2012). In an ongoing single centre clinical trial conducted in a routine clinical setting we distinguish benign from cancerous breast lesions within 2.5 hours using an atomic force microscope (AFM)-based method known as ARTIDIS. ARTIDIS employs a micro-fabricated 20nm-sharp tip which indents 10,000 locations/sample to measure the stiffness of cellular and matrix structures. In a comprehensive web-based platform we collect, verify and analyze these 2.54 millions of AFM indentations in relation to over 100 clinical parameters /patient using artificial intelligence. In our interim analysis of core needle and vacuum biopsies (N=254), 34 samples were classified as B1 (normal); 127 as B2 (benign); 12 as B3 (uncertain malignant potential); 0 as B4 (suspicious); 18 as B5a (ductal carcinoma in situ), and 58 as B5b (malignant). The diagnostic AFM ROC curve of B1 and B2 lesions vs. all B5 lesions (CI 95%; 100% sensitivity, 90% specificity, AUC = 0.98) demonstrated ARTIDIS outstanding ability to detect cancer in samples with &gt;80% neoplastic tissue. An analysis including lesions with &lt;5% neoplastic tissue, (CI 95%; 96% sensitivity, 74% specificity, AUC = 0.91) showed similarly outstanding results. The secondary comparison of B3 vs. B2 lesions could inform clinical practice as these overlapped significantly (CI 95%; 50% sensitivity, 88% specificity, AUC = 0.712) suggesting low malignancy potential; comparing B3 to B5a (CI 95%; 89% sensitivity, 83% specificity, AUC = 0.842) might be clinically relevant as B3 lesions similar to B5a lesions could be considered higher risk. Comparing Luminal A to Luminal B samples (CI 95%; sensitivity 83%, specificity 70%, AUC = 0.77) suggested a potential of ARTIDIS to distinguish a more aggressive Luminal B subtype with positive nodal status in 12 out of 23 patients. The results demonstrate the ability of ARTIDIS to differentiate benign from malignant breast lesions within 2.5 hours in a routine clinical setting. The secondary endpoint results suggest that we are able to subclassify breast lesions into specific subtypes. In particular, luminal B cancers exhibit nanomechanical profiles that could be associated with better or worse prognosis as confirmed by the post-AFM positive nodal status. The final analysis (n=508) will determine clinical utility for primary endpoint and indications for future studies on nanomechanical characterization of breast cancer for prediction and treatment optimization.
Citation Format: Rosemarie Burian, Ahmed Jizawi, Gabriel Zihlmann, Tobias Appenzeller, Philipp Oertle, Christian Raez, Roderick Y. Lim, Serafino Forte, Sophie Dellas, Simone Muenst, Tatjana Vlajnic, Ellen Obermann, Maria Ricci, Kevin Grimm, Ferdinand Niedermann, Marko Loparic, Marija Plodinec. A prospective, double-blinded clinical study using atomic force microscopy for fast diagnosis and subtyping of low and high-risk breast cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3140.