Abstract LB352: Unraveling the nanomechanical characteristics of invasive lobular carcinoma (ILC)

Abstract ILC is a distinct and aggressive subtype of breast cancer (BC) characterized by a unique single-file cell growth pattern and a propensity for diffuse metastasis, including leptomeningeal and peritoneal involvement. A hallmark of this disease is the loss of E-cadherin, a critical adhesion molecule, which disrupts cell-cell junctions and alters the mechanical properties of both cancer cells and their surrounding microenvironment. These changes contribute to the infiltrative behavior and metastatic potential of the disease. Understanding the mechanobiology of ILC offers promising avenues for targeted therapeutic interventions. Methods: Breast tissue (BT) samples from a blinded, single-center prospective study at the University of Basel’s Breast Clinic were analyzed. Nanomechanical properties were evaluated using the AFM-based Automated and Reliable Tissue Diagnostics (ARTIDIS) system on BT of patients (pts) with clinically indicated biopsy. All provided informed consent, with clinical data collected for up to 10 years(y). A total of 588 fresh BT samples from 545 pts suspected of BC were included, analyzed via the ARTIDISNET platform. Results: This study included 128 invasive BC patients (112 IDC, 16 ILC). Median ages were 62.8y (IDC) and 76.4y (ILC). Tumor characteristics were similar, but Ki-67 <10% was more common in ILC (56.3% vs. 27.7%), while >30% was higher in IDC (25% vs. 12.5%). Grade 3 tumors were also more frequent in IDC (32.1% vs. 18.8%). Nodal involvement was 37.5% in IDC and 12.5% in ILC. Tumor stages were similar, though stage II was more common in ILC (50% vs. 37.5%). Luminal A/B subtypes were 30.4%/45.5% (IDC) and 56.3%/31.3% (ILC). HER2+ was 15.1% (IDC) and 12.6% (ILC). Stiffness, adhesion, and dissipation profiles were significantly different between ILC and IDC, indicating that each cancer type has distinct mechanical properties. ILC exhibited higher stiffness overall, while IDC showed more consistent stiffness across samples. Additionally, ILC cells had lower dissipation compared to IDC, suggesting that ILC may have a stiffer tumor environment, possibly due to variations in tissue structure or extracellular matrix composition. When analyzing ILC subtypes (classical vs. variants), classical ILC showed a wider stiffness distribution, likely because its cells are more scattered. In contrast, ILC variants had a narrower stiffness range, indicating more clustered cell growth. Conclusion: This study provides a groundbreaking nanomechanical characterization of invasive lobular carcinoma (ILC) using ARTIDIS technology. It distinguishes ILC from invasive ductal carcinoma (IDC) based on unique stiffness and dissipation signatures while identifying aggressive ILC subtypes, surpassing current clinical technologies. These insights promise improved diagnostic precision and personalized therapies for ILC. The ANGEL trial, enrolling over 2,700 patients globally, is underway to further validate these findings. Citation Format: Marko Loparic, Carolina Ortiz Velez, Reiner Oropesa Nuñez, Sara Nizzero, Tobias Appenzeller, Leonie Briner, Rosemarie Burian, Christian Raez, Simone Muenst-Soysal, Tatjana Vlaijnic, Ellen Obermann, Sophie Dellas, Serafino Forte, Zlatko Marušić, Roderick Lim, Ahmed Jizawi, Philipp Oertle, Viola Heinzelmann-Schwarz, Marija Plodinec. Unraveling the nanomechanical characteristics of invasive lobular carcinoma (ILC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB352.