Mechanical fingerprints in breast cancer research: A multimodal experimental approach

Abstract Breast cancer remains the leading cause of cancer‐related mortality among women worldwide. Tumor biomechanics are not merely a symptom: they represent a functional signature with translational relevance in diagnostic, prognostic, and therapeutic resistance. Despite this, few experimental models are engineered to systematically investigate these physical properties across biological systems. Here, this study presents a multimodal biomechanical platform combining engineered 3D breast cancer spheroids with ex vivo tissue analysis to profile and compare viscoelastic behavior of healthy and tumoral environments. Rheometry and compression testing revealed a consistent mechanical shift in tumor‐derived samples marked by increased stiffness and force‐dependent nonlinear behavior, mirroring the ECM remodeling typical of aggressive phenotypes. This increased rigidity may adversely affect chemotherapy effectiveness by hindering drug delivery and altering cellular mechanotransduction. These biomechanical fingerprints enable quantitative discrimination between healthy and cancerous tissues and can serve as a surrogate marker of malignancy. By supporting the development of mechanics‐informed diagnostic tools, our platform offers a reproducible, clinically relevant framework to integrate biomechanical screening into translational breast cancer pipelines.