The IGFBP(3) family comprises six proteins with high affinity for the IGFs
and several lower affinity IGFBP-related proteins. Their production in the
breast is controlled by hormones, other local regulators and in tumors rela
tes to the estrogen receptor status. Their functional activity can also be
affected by various post-translational modifications. The IGFs are generall
y present at levels far in excess of that required for maximal receptor sti
mulation, and the IGFBPs are critical regulators of cellular action. IGFBPs
can affect cell function in an IGF-dependent or independent manner. ICF bi
oactivity locally in the breast is influenced not only by local tissue expr
ession and regulation of IGFs, IGFBPs, and IGFBP proteases, but also by the
se factors delivered from the circulation. Changes in the balance of the co
mponents of the IGF system may lead to a disruption of tissue homeostasis.