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Mutagenesis vol. 18 no. 4 pp. 395-399, July 2003
© 2003 UK Environmental Mutagen Society/Oxford University Press

Meeting Report

The Genotoxicity of Tamoxifen: Extent and Consequences, Kona, Hawaii, January 23, 2003

Miriam C. Poirier1 and Laura J. Schild

Carcinogen–DNA Interactions Section, Center for Cancer Research, Building 37, Room 4032, National Cancer Institute, 37 Convent Drive MSC-4255, National Institutes of Health, Bethesda, MD 20892–4255, USA

The current recommended adjuvant therapy for oestrogen receptor-positive breast cancer typically includes 20 mg/day tamoxifen (Nolvadex®) for 5 years post-operatively. This regimen has been found to reduce the incidence of contralateral breast cancer in breast cancer survivors by 47%, and, when used prophylactically, to reduce new breast cancers in high risk women by 49%. However, epidemiological evidence links tamoxifen therapy to increases in endometrial cancer and thromboembolic events in breast cancer patients. In addition, in tamoxifen-exposed rats dose-related increases in hepatic tamoxifen–DNA adduct formation and liver tumour incidence occur through a classic genotoxic mechanism. In women, endometrial cancers may be the result of genotoxicity, hormonally induced signal transduction and/or other mechanisms. If genotoxicity is relevant to tamoxifen-induced endometrial cancer it may be possible to identify women at risk through detection of tamoxifen–DNA adducts. The aim of this one day conference was to examine the most recent evidence for the occurrence of tamoxifen-induced genotoxicity in women receiving tamoxifen therapy. There were significant experimental differences, as some participants presented evidence for a genotoxic mechanism, while others reported finding insufficient evidence to support a genotoxic mechanism. The discussion was wide ranging and the outcome underscored the need for further investigations, access to more human tissue samples, shared tamoxifen–DNA standards for methodological comparisons and inter-laboratory exchange of human tissue samples.

1To whom correspondence should be addressed. Tel: +1 301 402 1835; Fax: +1 301 402 8230; Email: poirierm{at}exchange.nih.gov


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