Table 1 The ideal profile of a novel SERM in comparison with tamoxifen
Profile | Details |
|---|---|
Preclinical | Greater binding affinity for ER |
Ability to antagonize oestrogen dependent growth of breast cancer cells in vitro | |
Equal or greater inhibition of hormone-dependent xenograft growth in vivo | |
Activity against tamoxifen dependent (resistant) tumours | |
Delayed emergence of anti-oestrogen resistance in vivo | |
Reduced agonist effects in uterotrophic assays | |
Lack of stimulation of endometrial cancer cells in vitro/in vivo | |
Lack of DNA adduct formation | |
Prevention of bone loss in ovariectomized animals | |
Clinical | Activity in hormone sensitive breast cancer, at least equivalent to tamoxifen |
Increase in time to disease progression compared with tamoxifen | |
Activity in tamoxifen resistant breast cancer | |
Improved side effect profile (i.e. less hot flushes) | |
No endometrial thickening/hyperplasia/cancer risk | |
Preservation of bone mineral density | |
Reduction in serum cholesterol |