C2- and C4-position 17beta-estradiol metabolites and their relation to breast cancer: [review]

ABSTRACT

C2- and C4-position 17beta-estradiol metabolites play an important role in breast carcinogenesis. 2-Hydroxyestradiol and 4-hydroxyestradiol are implicated in tumorigenesis via two pathways. These pathways entail increased cell proliferation and the formation of reactive oxygen species that trigger an increase in the likelihood of deoxyribonucleic acid mutations. 2-Methoxyestradiol, a 17beta-estradiol metabolite, however, causes induction of apoptosis in transformed and tumor cells; thus exhibiting an antiproliferative effect on tumor growth. The 4-hydroxyestradiol2-methoxyestradiol and 2-hydroxyestradiol2-methoxyestradiol ratios therefore ought to be taken into account as possible indicators of carcinogenesis.