271P - First clinical demonstration of the predictive value of tissue nanomechanical signature in breast cancer patients in neoadjuvant therapy setting

Background

Structural remodeling of cells and extracellular matrix (ECM) during cancer initiation and progression are accompanied by substantial biomechanical alterations, which can be measured by Atomic Force Microscopy (AFM). Increasing (pre)- and clinical evidence demonstrate the importance of cancer biomechanics in mediating therapy response. 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

We conducted a single center, blinded, prospective study to measure a multiparameter nanomechanical signature (NS) of response to neoadjuvant therapy (NAT) in breast cancer (BC). Between 2016 and 2019, 588 fresh, baseline, clinical breast biopsy samples from 545 patients were measured using the AFM based Automated and Reliable Tissue Diagnostics (ARTIDIS) investigational device – ART-1, within routine clinical setting in the Breast Clinic, University Hospital Basel. 35 patients received NAT: combination chemotherapy (CHT) (n=30) and endocrine NAT (n=5). Study endpoints were radiological complete response (rCR) prior and pathological complete response (pCR) after surgery. NS data has been analyzed in an automated manner using proprietary ARTIDISNet software platform. 10 y follow up is ongoing.

Results

The ARTIDIS NS of response to NAT in BC showed 100% negative predictive value (NPV) and 89% positive predictive value (PPV) with 93% of accuracy for patients receiving CHT, independent of molecular subtype or treatment regimen. Sensitivity was 100% and specificity was 85% (AUC=0.91). When 5 patients with endocrine NAT were included, performance was decreased, meaning: NPV=92%, PPV=91, Sensitivity = 95 and Specificity = 85 (AUC=0.83).

Conclusions

NS can be prospectively used in clinical settings to predict response to NAT in BC. Mechanistically, these results highlight the importance of cell and TME mechanics in modulating therapy response. Furthermore, these results are being validated in a multicenter prospective study (ANGEL) currently enrolling 2706 patients with the aim to support implementation of the ARTIDIS NS into routine clinical practice.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

ARTIDIS AG.

Funding

ARTIDIS AG.

Disclosure

S. Nizzero: Financial Interests, Personal, Other, Travel cost: ARTIDIS AG; Financial Interests, Personal, Advisory Role: ARTIDIS AG. T. Appenzeller, P. Oertle:: Other, Personal and Institutional, Leadership Role: ARTIDIS AG. L. Briner: Non-Financial Interests, Institutional, Research Funding: ARTIDIS AG. R.A. Burian: Non-Financial Interests, Institutional, Principal Investigator: ARTIDIS AG. A. Jizawi: Financial Interests, Institutional, Leadership Role: ARTIDIS AG. S. Schädelin: Financial Interests, Institutional, Financially compensated role: ARTIDIS AG. C. Raez: Financial Interests, Institutional, Other: ARTIDIS AG. S. Muenst-Soystal, T. Vlajnic, E. Obermann: Other, Institutional, Non financial benefits: ARTIDIS AG. S. Dellas, S. Forte: Other, Institutional, Non remunerated activity: ARTIDIS AG. Z. Marušić: Financial Interests, Personal and Institutional, Financially compensated role: ARTIDIS AG. P.D. Ndiaye, G. Zaugg: Other, Personal and Institutional, Affiliate: ARTIDIS AG. M. Loparic, M. Plodinec: Other, Personal and Institutional, Officer: ARTIDIS AG.