Engineering Complexity: Advances in 3D Breast Cancer Models for Precision Oncology.

Engineered in vitro cancer models are essential tools in cancer research, offering controlled microenvironments to study tumor biology and develop personalized therapies. Breast cancer, known for its complexity and high cellular heterogeneity, poses significant challenges in treatment. To address this, patient-derived in vitro breast cancer models are being used to better predict individual drug responses and guide therapy selection. Recent bioengineering efforts have focused on replicating key features of breast cancer in vitro, such as angiogenesis, tumor cell invasion, heterogeneity, interactions with the tumor microenvironment, and metastatic behavior. Technologies including organoids, microfluidic platforms, and 3D bioprinting technologies have enabled the creation of more biologically and physiologically relevant models. Each system offers specific strengths and limitations, and choosing the right model depends on the research question and desired complexity. This review highlights the current progress in engineering in vitro breast cancer models, comparing their capabilities and discussing innovations aimed at improving their biological accuracy and clinical relevance. Ongoing challenges and future directions are also addressed, with a focus on enhancing model fidelity to native breast cancer.