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It has been proposed that a shift toward 2-hydroxyestrone (2-OHE1) from the 16α-hydroxyestrone (16-OHE1) metabolic pathway may be inversely associated with breast cancer risk because 2-OHE1 is thought to be less genotoxic and estrogenic than 16-OHE1. In the recently published study of Arslan and colleagues [1], serum levels and the ratio of the estradiol metabolites 2-OHE1 and 16-OHE1 were investigated in 377 incident premenopausal women and 377 matched controls and the risk of breast cancer was calculated. No significant associations between breast cancer risk and estradiol metabolite concentrations were observed.


  • Alfred O. Mueck
    Head of the Department of Endocrinology and Menopause; Head of the Center of Womens Health, University Womens Hospital, Tuebingen, Germany


  1. Arslan AA, Shore RE, Afanasyeva Y, et al. Circulating estrogen metabolites and risk for breast cancer in premenopausal women. Cancer Epidemiol Biomarkers Prev 2009;18:22739. Published August, 2009.
  2. Yager JD, Davidson NE. Estrogen carcinogenesis in breast cancer. N Engl J Med 2006;354:270-82.
  3. Lippert TH, Seeger H, Mueck AO. Estrogens and the cardiovascular system: role of estradiol metabolites in hormone replacement therapy. Climacteric 1998;1:296-301.
  4. Mueck AO, Seeger H, Lippert TH. Estradiol metabolism and malignant disease. Maturitas 2002;43:1-10.
  5. Seeger H, Wallwiener D, Krmer E, et al. Comparison of possible carcinogenic estradiol metabolites: effects on proliferation, apoptosis and metastasis of human breast cancer cells. Maturitas 2006;54:72-77.
  6. Osborne MP, Bradlow HL, Wong GY, et al. Upregulation of estradiol C16 alpha-hydroxylation in human breast tissue: a potential biomarker of breast cancer risk. J Natl Cancer Inst 1993;85:1917-1920.
  7. . Bradlow HL, Hershcopf RJ, Martucci CP, et al. Estradiol 16alpha-hydroxylation in the mouse correlates with tumor incidence and presence of murine mammary tumor virus: a possible model for the hormonal etiology of breast cancer in humans. Proc Natl Acad Sci USA 1985;82:6295-9.
  8. Seeger H, Zimmermann B, Brunner S, et al. Estradiol metabolites in postmenopausal women with and without breast cancer a case control study. Senologie 2008;5:211.
  9. Mueck AO, Seeger H. Breast cancer: are estrogen metabolites carcinogenic? Climacteric 2007;10(Suppl2):62-5.
  10. Cogliano V, Grosse Y, Baan R, et al.; WHO International Agency for Research on Cancer. Carcinogenicity of combined oestrogen-progestagen contraceptives and menopausal treatment. Lancet Oncol 2005;6:552-3.
  11. Schneider HP, Mueck AO, Kuhl H. IARC Monographs on carcinogenicity of combined hormonal contraceptives and menopausal therapy. Climacteric 2005;8:311-16.
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