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

M. C. Poirier
2003 Mutagenesis  
The current recommended adjuvant therapy for oestrogen receptor-positive breast cancer typically includes 20 mg/ day tamoxifen (Nolvadex â ) 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
more » ... boembolic 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 signi®cant experimental differences, as some participants presented evidence for a genotoxic mechanism, while others reported ®nding insuf®cient 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.
doi:10.1093/mutage/geg005 pmid:12840114 fatcat:z4wk2hcuovajnfvlkjmho4uqge