Volume 3 Supplement 1

23rd Congress of the International Association for Breast Cancer Research

Open Access

The mechanism of tamoxifen in breast cancer prevention

  • F Yu1 and
  • W Bender1
Breast Cancer Research20013(Suppl 1):A74

https://doi.org/10.1186/bcr404

Received: 10 May 2001

Published: 31 May 2001

Tamoxifen (TAM) is known to have a dual mechanism of action: (1) to compete with 17β-estradiol (E2) at the receptor site and to block the promotional role of E2 in breast cancer; and (2) to bind DNA after metabolic activation and to initiate carcinogenesis. Recent large clinical trials indicate that TAM is also an effective chemopreventive agent against breast cancer. The mechanism is unknown. Because E2 requires activation by epoxidation to bind DNA forming DNA adducts [1], and the same is true for TAM [2], the question is whether this preventive effect of TAM against breast cancer is contributory to the possibility that TAM, as an effective competitor for epoxidation, prevents the formation of E2 epoxide and consequently breast cancer. Evidence will be presented to show that, indeed, when incubated together with E2 for epoxidation, TAM was able to dramatically reduce the formation of E2 epoxide as measured by both the loss of the ability of E2 to inhibit nuclear RNA synthesis, and the reduced binding of [3H]labeled E2 to nuclear DNA. Identical results were obtained when TAM and estrone (E1) were used. These results suggest that the breast cancer preventive effect of TAM is through a competitive epoxidation mechanism with E1/E2.

Authors’ Affiliations

(1)
Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford

References

  1. Yu FL, et al: A hypothesis on breast cancer. In: The 22nd Congress of International Association for Breast Cancer Research; September 25-28. 1998, 19-24. Düsseldorf, Germany. 13-16 June 2001, ; Athens, Greece. Edited by Ioannidou-Mouzaka L, Agnantis NJ, Lopez DMGoogle Scholar
  2. Phillips DH, et al: Carcinogenesis. 1994, 15: 793-795. Düsseldorf, Germany. 13-16 June 2001View ArticlePubMedGoogle Scholar

Copyright

© BioMed Central Ltd 2001

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