The Role of Selective Estrogen Receptor Modulators on Breast Cancer: From Tamoxifen to Raloxifene

Abstract

The link between hormones and breast cancer growth and development has been recognized for more than a century. Estrogen stimulates the proliferation of breast epithelial cells, and both endogenous and exogenous estrogens have been implicated in the pathogenesis of breast cancer. Classically, estrogen action at target sites around the body is mediated through related but distinct estrogen receptors (ERs), designated ERalpha and ERbeta, to alter gene expression. This accumulating understanding of the mechanism of action of estrogen led ultimately to the design of antiestrogenic agents that work by virtue of their interaction with the ER; these drugs have come to be known as selective estrogen receptor modulators (SERMs). Tamoxifen, a SERM, emerged as the first antiestrogenic agent that is clinically applicable to breast cancer. Tamoxifen became the "gold standard" and established the principles of tumor targeting and identified the appropriate treatment strategy to aid survivorship in breast cancer patients, with enhancement of disease-free survival and a 50% decrease in recurrences observed in ER-positive patients 15 years after diagnosis. However, because of the many adverse events in the use of tamoxifen, some of which have contributed to significant morbidity and mortality, drug modification which has resulted in fewer incidences of adverse events without compromising the therapeutic effect for breast cancer prevention may face an easier road to acceptance. Raloxifene may be a better alternative, since evidence from large clinical trials showed that raloxifene not only decreases the incidence of osteoporosis and related fractures, but also offers benefits for breast cancer prevention. The results from the Study of Tamoxifen and Raloxifene (STAR) trial showed the superiority of raloxifene over tamoxifen, not only for the equal efficacy in the prevention of invasive breast cancer but also for the fewer serious adverse events. Taken together, without other competition so far, raloxifene is recommended for postmenopausal women with osteoporosis who also need breast cancer prevention.

Effect of single mutagenesis on the binding pocket of canine estrogen receptor alpha: Structure and binding affinity

“…It should be kept in mind that different algorithms could give rise to different structural prediction and possibly different binding affinities [21,[24][25][26] . The acquired SERM resistance in breast cancer cells has been studied, especially with respect to long-term treatment [27][28][29][30][31][32] . Interestingly, ER expression is maintained in the acquired resistant tumors [29] .…”

Nanoemulsion liquid preconcentrates for raloxifene hydrochloride: optimization and in vivo appraisal

“…15,27 Preparation of RLX-loaded SNEDDS Preparation of nonalkalinized nanocarriers (NA-SNEDDS) RLX was added to the selected formulations based on the aforementioned optimization steps. The drug was added in incremental amounts (2,5,10,20,30,40,50, 60 mg/g), and dispersion was gently shaken at 60°C for 30 minutes. Shaking was aided by sonication and vortex mixing.…”

“…RLX in incremental amounts (2,5,10,20,30,40,50, 60 mg/g) was added to SNEDDS alkalinized with triethanolamine (TEA) (10% weight/weight [w/w]). Dispersion was gently shaken at 60°C for 30 minutes.…”

“…However, there is an association between the risk of breast cancer and persistently elevated blood levels of estrogen. 2 Recently, selective estrogen-receptor modulators (SERMs) have represented a major therapeutic advance for clinical practice. SERMs work by virtue of their interaction with the estrogen receptors.…”

Microgenomic approaches to identify clinically relevant gene signatures that discriminate histologic types of breast carcinomas.

“…One of the therapeutic approaches involves blocking the ability of the ER protein to bind native estrogen molecules in a cell, thus inhibiting its action. This type of treatment utilizes manmade drugs called antiestrogens (also called SERMs, Selective Estrogen Receptor Modulators), such as the drug Tamoxifen (15,16,24).…”