Mechanisms of disease: adipokines and breast cancer - endocrine and paracrine mechanisms that connect adiposity and breast cancer.

A vast number of epidemiological studies suggest an important, but still controversial, role for obesity and adipose tissue mass in breast cancer risk and an association with tumor phenotype. The main conclusions from these studies raise the possibility that the adipose tissue can act as an effector organ that influences both cancer risk and tumor behavior. Here we also review heterotypic mechanisms in breast-cancer tumorigenesis; these mechanisms involve soluble secreted factors from peritumoral cells, extracellular-matrix components and interactions between stromal cells and tumor cells that create a specific and local peritumoral microenvironment. As a special focus, we discuss the increasing evidence for a role of peritumoral adipose tissue and secreted adipokines (such as adiponectin and leptin) in breast cancer; furthermore, the cellular and molecular basis of the peritumoral 'desmoplastic' tissue reaction observed in breast cancer is reviewed in detail.