**11. Concept of selective oestrogen receptor modulation**

SERMs are estrogenic and antiestrogenic molecules that have a wide range of effects. Two SERMs are now accessible in clinical trials: tamoxifen for breast cancer prevention and raloxifene for osteoporosis prevention. Tamoxifen was first created as an antiestrogen to treat breast cancer. Tamoxifen's widespread use as a therapy for all stages of ER-positive breast cancer in men and women has been assisted by its low risk of adverse effects. Concerns about the effects of an antiestrogen on bone density and the risk of CHD were raised when the strategy of testing long-term (5 years) tamoxifen therapy in ER-positive, lymph node-negative women and the proposed testing of tamoxifen as a preventive agent in high-risk women were proposed in the mid-1980s. Tamoxifen, on the other hand, is not a pure antiestrogen; it has antiestrogenic as well as estrogenic properties [56]. According to laboratory studies, tamoxifen is a selective oestrogen in areas like bone but an antiestrogen in breast tissue, preventing carcinogenesis and tumour development. Laboratory investigations dating back to the 1980s [57, 58] have confirmed raloxifene's SERM activity.

#### **11.1 Mechanisms of action**

Even though exact molecular mechanism of oestrogen or SERMs at the ER is unknown, two ERs govern oestrogen activity in target tissues: 1) ER, the traditional ER [59]; and 2) ER, which controls the action of ER and decreases tamoxifen's oestrogen-like effects [60, 61]. Although the crystal structure of the whole ER has yet to be determined by x-ray crystallography, data on the ligandbinding domains conjugated with estrogens and SERMs has been published. The outer forms of oestrogen and SERM complexes have been better understood as a result of this information. Oestrogen receptors (ERs) are nuclear transcription factors that bind estrogens, dimerize, and form a transcription complex with coactivators and other molecules to help unwind DNA. At oestrogen-responsive genes, RNA polymerase produces messenger RNA. SERM–ER complexes appear to alter the signal transduction route to oestrogen-responsive genes (through oestrogen response elements [EREs]) by binding a corepressor protein or activating fewer or different coactivators. This is, however, a simplistic model of oestrogen and antiestrogen action that overlooks the nuances of SERM function.

### **12. Drugs repurposed for breast cancer treatment**

The commercially approved drugs that were originally used for diseases other than breast cancer are discussed in the following section. These medicines, on the other hand, are now being used or researched for breast cancer treatment. The drug candidates repurposed for breast cancer are divided into categories based on how they work (**Table 2**).


**Table 2.**

*A list of repositioned drugs approved for breast cancer treatment.*
