Post-menopausal breast cancer risk: oral estrogen treatment and abdominal obesity induce opposite changes in possibly important biological variables.

Almost all of the epidemiological studies on the consequences of estrogen replacement treatment (ERT) refer to subjects treated with oral conjugated equine estrogens (CEE). These studies suggest that breast cancer (BC) risk is limited and can only be seen after long-term and/or high dosage use. Orally administered estrogens present a number of metabolic and endocrine peculiarities, some of which could be important in reducing the risk to the breast. Actually, these peculiarities are opposite to those observed in post-menopausal women with abdominal obesity (AO), a group which has recently been identified to be at high risk. AO (as other situations in which an increase in BC risk does exist) shows a sex-hormone-binding-globulin (SHBG) level reduction, which causes an increase of both estrogenic and androgenic activity. Further features of AO, possibly involved in BC risk, could be: i) increased free fatty acid (FFA) levels; ii) hyperinsulinemia; iii) increase of circulating insulin-like growth-factor-I (IGF-I) activity. On the contrary oral estrogens, through their hepatocellular effects, cause: i) a clearcut SHBG increase; ii) a trend to reduced circulating IGF-I activity. As a consequence, the possibility that oral estrogens are characterized by a favourable balance between estrogenic activity and biological modifications protective to the breast, is worth consideration. Even non-oral estradiol have a possible protective action through FFA level reduction; however, due to the absence of hepatocellular effect, it does not influence SHBG levels and IGF-I activity. It seems difficult to extend data on the relationship between BC and oral CEE to other types of types of ERT. For the latter, further study will be necessary.