There are studies in the literature where women have been given tamoxifen for upwards of 5 years continuously with no mention of an increase incidence of liver cancer. The primary concern has always been the induction of endometrial cancer since tamoxifen can have estogenic effects in the uterus (see below). Tamoxifen does have some documented toxic effect on the liver and noone can guarantee that this toxic effect will not ultimatley lead to cancer, however there is no real evidence in the literature outside of animal tests. My opinion is that the "toxicity" of tamoxifen is overblown and that if someone is really concerned, the newer serms seem to have better safety profiles.
Breast J. 2002 Mar-Apr;8(2):92-6.
Toxicity of antiestrogens.
Hirsimäki P, Aaltonen A, Mäntylä E.
Department of Pathology, Turku University Central Hospital, BioCity, Tykistökatu B.8.6., FIN-20520 Turku, Finland.
[email protected]
Abstract
The object of this article is to review briefly the preclinical and clinical safety of some antiestrogens. Tamoxifen, toremifene, droloxifene, and idoxifene are polyphenylethylene antiestrogens, whereas the pure antiestrogen, ICI 182,780 or faslodex, as well as raloxifene, is of a different structure. Tamoxifen has been shown to be genotoxic in several studies. It induces unscheduled DNA synthesis in rat hepatocytes and micronuclei in MCL-5 a cells in vitro. Tamoxifen also induces aneuploidy in rat liver in vivo and chromosome aberrations and micronuclei in mouse bone marrow. Toremifene has also shown to be genotoxic, but to a far lower extent, by inducing micronuclei in MCL-5 a cells in vitro and by inducing aneuploidy in rat liver in vivo. Tamoxifen has been shown to be hepatocarcinogenic in the rat in at least four independent long-term studies. The initiation of tumors in the rat is the result of metabolic activation by cytochrome P450 isoenzymes to an electrophile(s) that binds irreversibly to DNA. The other antiestrogens have not been shown to be carcinogenic in rodents. In several independent clinical studies, the risk of endometrial cancer has increased among tamoxifen-treated women. After reviewing the available data, the International Agency for Research on Cancer concluded that there was sufficient evidence to show that tamoxifen is a class I human carcinogen. The increased risk for endometrial cancer occurs predominantly among women who are 50 years old or older and who have been treated with tamoxifen. It is not yet clear whether the uterine tumor formation is a result of genetic mechanisms, analogous to those seen in the rat liver or due to the estrogen agonist action of tamoxifen. However, the other antiestrogens with a more or less similar intrinsic estrogenic potential have not been shown to be carcinogenic in humans.
PMID: 11896754 [PubMed - indexed for MEDLINE]
