Breast cancer: further metabolic-endocrine risk markers?

There is evidence that increased oestrogen receptor (ER) expression in normal mammary epithelium may be a risk marker for the development of breast cancer. Insulin-like growth factor 1 (IGF1) is a potent inducer of mitosis and has been shown to synergize with oestrogen in stimulating the growth of human breast cancer in vitro. In these cells oestradiol has been shown to upregulate IGF type 1 receptor (IGFR), and recently a similar effect has been reported in normal human breast tissue xenografts in vivo. It has been postulated that the combined effect of oestradiol and IGF1 may stimulate proliferation in normal mammary epithelium and increase breast cancer risk. The bioavailability of IGF1 to the tissues is modulated by IGF-binding proteins (IGFBPs), and higher circulating levels of IGF1 and lower levels of IGFBP3 have been reported in breast cancer patients. Breast cancer specimens show a positive correlation between ER status and IGF receptor status, and also a negative correlation between ER status and IGFBP3 expression. Finally, ectopic growth hormone expression has been shown in a majority of specimens of normal and malignant breast tissue, and this may contribute to breast cancer risk, possibly by increasing the local level of bioavailable IGF1. Expansion of such findings may provide clinically useful markers of increased risk to breast cancer in women.