POTENTIAL IMPACT ON BREAST-CANCER RISK OF CIRCULATING INSULIN-LIKE GROWTH-FACTOR-I MODIFICATIONS INDUCED BY ORAL HRT IN MENOPAUSE

Unlike parenteral estrogens, oral estrogen administration in menopause causes, through its hepatocellular action, a significant decrease of circulating insulin-like growth factor I (ICF-I) levels; this effect i s opposed by the addition of an androgenic progestogen. In vitro studi es show that ICF-I is a potent mitogen for 'estrogen responsive' breas t cancer cells. Moreover, some Endings in breast cancer patients and i n women treated with tamoxifen suggest that reduction of circulating I CF-I could be protective to the breast. However, by also considering ( 1) the potential action on breast cancer cells of ICF-II, (2) the poss ible consequences of the growth hormone (GH) increase caused by the IG F-I reduction and (3) the fact that in vitro results are not simply tr ansferable to the in vivo condition, other 'scenarios' can be envisage d, besides the favorable one. In support of the latter, there are epid emiologic data which suggest that oval estrogen use could have some fa vorable peculiarities with regards to breast cancer risk. The associat ed decrease in circulating IGF-I level could well be one of these pecu liarities.