Shaping breast cancer progression in obesity: Insights from advanced models and omics tools

Obesity is a negative prognostic factor in BC, a heterogeneous and complex disease representing the leading cause of mortality from female cancer. Within the breast tumour microenvironment (TME), adipocytes, fibroblasts, immune cells and the extracellular matrix are aberrantly activated in obesity, leading to inflammatory responses, together with hormonal and metabolic changes, and activation of oncogenic pathways that facilitate disease progression. To fully grasp the metabolic complexity and heterogeneity of obese BC patients, proper experimental models, able to mimic the aberrant interactions occurring within the obese breast TME, are required. Herein, we first present the most recent findings on the players involved in the remodelling of the breast TME during obesity. Next, we highlight the main advanced preclinical models used to investigate the interaction between obesity and BC, including immunocompetent and immunodeficient in vivo systems, as well as advanced 3D in vitro and ex vivo models. We focus on the integration of these models with advanced omics techniques, such as transcriptomics, proteomics and metabolomics, toward a more systematic and dynamic view of the obesity-BC link. Finally, we discuss the current limitations of available models and the future prospects to advance knowledge in the field.