Tamoxifen-induced endometrial cancer
Shibutani, Suzuki, and Grollman
Tamoxifen is the principal antiestrogen used in adjuvant therapy for breast cancer with more than 500,000 women in the U.S. being treated with this drug. Tamoxifen also reduces the incidence of breast cancer in women at high risk of developing this disease. Unfortunately, tamoxifen therapy is associated with the development of endometrial cancer, a significant risk for otherwise healthy women who take this drug over extended periods of time.
We have developed a highly sensitive and specific method for measuring tamoxifen-DNA adducts in women treated with this drug. The level of adducts detected in endometrial tissue, coupled with their mutagenic properties, suggests that a genotoxic mechanism may be responsible for its carcinogenic effects. The marked inter-individual variation in the level of tamoxifen-DNA adducts reflects activities of enzymes involved in tamoxifen metabolism or differences in adduct repair. These observations promoted a study of the toxicogenomics of tamoxifen to identify women at risk of endometrial cancer and help in designing safer drugs for the chemoprevention of breast cancer.
- Shibutani, S., Suzuki, N. and Grollman, A.P. Tamoxifen-DNA adducts: biomarkers for drug-induced endometrial cancer in Biomarkers of environmentally associated disease: technology, concepts and perspectives, ed by S.H. Wilson and W.A. Suk. CRC Press LLC,
- Shibutani, S. Ravindernath, a., Suzuki, N., Terashima, I., Sugarman, S.M., Grollman, A.P and