Breast cancer: are oestrogen metabolites carcinogenic?
The World Health Organization (WHO) classified oestrogens as carcinogenic in humans. One of the main arguments has been that oestrogens not only can promote cancers but also may initiate mutations caused by certain oestrogen metabolites. Indeed there is evidence that they can have biological properties even at very low concentrations which can exceed manifold those of their parent substance. Highly sophisticated laboratory methods will allow us to understand oestrogenic effects as a net effect of the corresponding metabolite pattern. Current research focuses on the possible carcinogenic properties of 4-hydroxyoestrogens and 16-alpha-hydroxyoestrone, but also on the anticancerogenic effects particularly of 2-methoxyoestradiol. Thus, potential toxic secondary metabolites like 4-quinones can be eliminated, e.g. by methylation. 2-methoxyoestradiol is a potent antiproliferative and antiangiogenic metabolite, and is currently tested in patients with refractory metastatic breast cancer. Observational trials have demonstrated that the ratio of 2- to 16-alpha-hydroxyoestrone is decreased in women with breast cancer. We have been able to demonstrate that oestradiol metabolism during HRT can be influenced by administration route, possibly also by certain progestogens. In in vitro and animal experiments certain oestrogen metabolites indeed can act as carcinogens. However, since for the formation of these metabolites the appearance of very special conditions is a prerequisite and also various protective mechanisms are present, this might only contribute to breast carcinogenesis in very rare cases. However, the clinical relevance remains unclear and it appears to be important to ascertain this issue.
Mueck
Alfred O
AO
University Women's Hospital of Tuebingen, Tuebingen, Germany.
Seeger
Harald
H
D000818:Animals; D001943:Breast Neoplasms / Q000139:chemically induced*; D002273:Carcinogens / Q000378:metabolism*; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D045166:Estradiol Congeners / Q000009:adverse effects* / Q000378:metabolism*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D005260:Female; D006801:Humans
D002273:Carcinogens; D045166:Estradiol Congeners