Title | The molecular basis of breast cancer prevention and treatment: the role of tissue-specific antiestrogens | |
Authors | M.N. Alexis, D. Siriani and C.E. Sekeris
Molecular Endocrinology Program, Institute of Biological Research and Biotechnology, the National Hellenic Research Foundation, Athens, Greece |
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Citation | Alexis, M.N., Siriani, D., Sekeris, C.E.: The molecular basis of breast cancer prevention and treatment: the role of tissue-specific antiestrogens, Epitheorese Klin. Farmakol. Farmakokinet. 14(1): 5-14 (2000) | |
Publication Date | Received for publication: 20 November 1999
Accepted for publication: 5 December 1999 |
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Full Text Language | English | |
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Keywords | Estrogens, antiestrogens, breast cancer, prevention, treatment. | |
Other Terms | review article | |
Summary | Although estrogens increase the risk to develop breast and/or endometrial cancer, they also help women to maintain bone mass and proper cardiovascular system functions. Antiestrogens that can effectively block the action of estrogen in the reproductive system while mimicking it in the cardiovascular and skeletal systems need to be developed for long-term use in breast cancer prevention and therapy. Tamoxifen, a first-line agent in widespread use for breast cancer therapy for many years that was recently approved for long-term preventive use also, has been shown to increase endometrial cancer risk and to poorly mimic estrogen action in the skeletal and cardiovascular systems. Raloxifene, a third generation antiestrogen initially introduced for the treatment of osteoporosis, is currently under scrutiny for breast cancer prevention and treatment (the MORE trial) and for cardiovascular system maintenance (the RUTH trial). The STAR trial was launched in 1998 to compare the effectiveness of these two agents. Preliminary findings suggest, however, that the outcome is likely to strengthen the view that effective tissue-specific antiestrogens are yet to be developed. In the light of recent advances in our understanding of the molecular basis of tissue-specific antiestrogen action, a model of breast cancer progression to antiestrogen resistance is presented that may help to pinpoint molecular end-points that should be taken into account when screening for effective tissue-specific antiestrogens. | |
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