Application of selective estrogen receptor modulators for breast cancer treatment according to their intrinsic nature.

The selective estrogen receptor modulators (SERMs) tamoxifen and raloxifene exert their estrogen agonist and antagonist actions depending on the target organ and individual circumstances. For instance, tamoxifen increases bone mineral density in postmenopausal patients, but decreases it in premenopausal patients when it is used as the adjuvant therapy for breast cancer in both populations. Due to positive results from recent large clinical trials for early breast cancer, the aromatase inhibitors (AIs) are the agent of first choice for postmenopausal patients. However, the veteran SERM tamoxifen is still the primary drug for premenopausal breast cancer patients, patients with ductal carcinoma in situ and subset of postmenopausal women. Recent accumulated data suggest that both raloxifene and tamoxifen could be useful in chemoprevention. Further investigation should be made into the development of a systematic strategy for application to a suitable target population, i.e., one more likely to develop hormone receptor-positive breast cancer. Unlike the AIs, SERMs have a distinct function that does not directly relate to hormone receptors when used in higher pharmacological concentration. The attempt to overcome chemo-drug resistance using high-dose SERMs would be one approach to developing such a strategy. There were several reports showing the antiproliferative effect of SERMs for estrogen receptor-negative cells, such as glioma. There are still numerous possible applications for SERMs when their intrinsic nature is utilized.