Adipokines (leptin, adiponectin, and hepatocyte growth factor (HGF)) secreted 
from adipose tissue have come to be recognized for their contribution to the 
mechanisms by which obesity and related metabolic disorders influence breast 
cancer risk. In this review, we discuss the direct and indirect effects of these 
protein factors on the biological and clinical aspects of breast cancer biology, 
and emphasize their distinctive modes of action through endocrine-, paracrine-, 
and autocrine-mediated pathways. The stimulatory effects of leptin on breast 
cancer growth were considered to occur primarily via activation of the estrogen 
receptor; however, new evidence suggests that leptin may be acting on downstream 
cell signaling pathways in both estrogen-dependent and -independent cell types. 
Another secretory adipokine, HGF, may act largely not only to promote tumor cell 
invasion, but also to enhance tumor growth indirectly by stimulating 
angiogenesis. In contrast, adiponectin, an endogenous insulin sensitizer, exerts 
a direct growth-inhibitory effect on tumor cells by downregulating cell 
proliferation and upregulating apoptosis, and also inhibits tumor-related 
angiogenesis.