Abstract 6394: Tissue nanomechanical signature predicts response to neoadjuvant chemotherapy in patients with breast cancer
Authors: Mariam Gachechiladze, Sara Nizzero, Tobias Appenzeller, Leonie Briner, Rosemarie Burian, Sabine Schädelin, Simone Muenst-Soysal, Tatjana Vlaijnic, Ellen Obermann, Sophie Dellas, Serafino Forte, Zlatko Marušić, Ahmed Jizawi, Papa Diogop Ndiaye, Philipp Oertle, Gregory Zaugg, Marko Loparic, Marija Plodinec
Journal: Cancer Research (2024)

Abstract Background: Neoadjuvant chemotherapy (NACT) is increasingly used in patients with breast cancer. However, predicting response to NACT remains a challenge in everyday clinical practice. Increasing (pre)- and clinical evidence demonstrate the importance of cancer biomechanics in mediating therapy response. We and others have previously demonstrated that complex biomechanical alterations in cancer tissues, can be measured by the Atomic Force Microscopy (AFM) at the nanoscale level. Incorporating AFM measurements of clinical biopsies within standard of care is thus a promising avenue to leverage tissue mechanics as prognostic and predictive biomarker for solid cancers. Methods: Fresh clinical biopsy samples from 545 breast cancer patients were measured using the AFM-based Automated and Reliable Tissue Diagnostics (ARTIDIS) investigational device - ART-1. Measurements were performed on baseline biopsies within routine clinical workflow in the Breast Clinic, University Hospital Basel. This cohort comprises 30 patients who received NACT including: anthracycline and/or taxane based chemo (n=17), and anthracycline and/or taxane with platinum chemo (n=13). Study endpoints were radiological complete response (rCR) prior and pathological complete response (pCR) after surgery. Multiparametric nnanomechanical signature data has been analyzed in an automated manner using the proprietary ARTIDISNET software platform. Results: From the 30 patients who received NACT, 12 patients presented with rCR, 17 patients presented with rPR, and 1 patient presented with rNR. pCR has been achieved only in 9 patients. In this study, he ARTIDIS nanomechanical signature of response to NACT in breast cancer showed 100% negative predictive value (NPV) and 89% positive predictive value (PPV), with 93% of accuracy for patients receiving chemotherapy, independent of molecular subtype or treatment regimen. Sensitivity was 100% and specificity was 85% (AUC=0.91). Conclusion: ARTIDIS nanomechanical signature can be seamlessly integrated within clinical settings to predict response to standard of care NACT in patients with breast cancer in a prospective manner. These results are currently being validated in a global, multicentre prospective study in breast cancer (ANGEL, NCT06085833), enrolling in total 2706 patients, with the aim to support implementation of the ARTIDIS nanomechanical signature into routine clinical practice. Citation Format: Mariam Gachechiladze, Sara Nizzero, Tobias Appenzeller, Leonie Briner, Rosemarie Burian, Sabine Schädelin, Simone Muenst-Soysal, Tatjana Vlaijnic, Ellen Obermann, Sophie Dellas, Serafino Forte, Zlatko Marušić, Ahmed Jizawi, Papa Diogop Ndiaye, Philipp Oertle, Gregory Zaugg, Marko Loparic, Marija Plodinec. Tissue nanomechanical signature predicts response to neoadjuvant chemotherapy in patients with 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 6394.