Advancing ER-positive breast cancer risk reduction from traditional SERMs to heterocyclic scaffolds and dual SERM-SERD combinations”

Background: Breast cancer is most prevelant non skin cancer in women and ER-positive
breast cancer , is considered second leading cause of cancer related mortality .Driven by
estrogen signalling , is the most prevelant subtype worldwide.This narrative review explores
riskfactors ,assessment tools,and summarizes the effectiveness and side effects of
chemopreventive agents used for breast cancer risk reduction. Selective estrogen receptor
modulators (SERM)remain essential therauptics ,antagonizing estrogen activity in breast
tissue while retaining agonist effect in bones and CVS.
Methodology: While traditional reviews have focused on triphenylethylene and
benzothiophene scaffolds, heterocyclic SERMS-including indole, bezimidazole, coumarin,
benzopyran . Raloxifene has better safety profiles compared to tamoxifene. AI,like
anastrazole and exemestane,reduce invasive breast cancer at the same time tamoxifen mimics
estrogen there ,it can cause the uterine lining to thicken, slightly increasing the risk of uterine
cancer.
Results: Tamoxifene, a selective estrogen receptor modulator(SERM)demonstrated efficacy
in reducing breast cancer risk in postmenopausal and premenopausal women . Major
limitations include incomplete receptor subtype selectivity,metabolic instability,partial
agonism in nontarget tissues this work uniquely integrates structural,mechanistic ,and
therauptic insights including dual SERM-SERDscaffolds combination with aromatase
inhibitors and computationally guided subtype -selective design to overcome
resistance,improve potency,and optimize clinical outcomes in ER-POSITIVE breast cancer
therapy.
Conclusion: Chemopreventive agents present oppurtunities in reduction of breast cancer
further research is needed to compare the effectiveness of SERMs and AI, especially in high
risk populations with pathogenic germiline mutation Keywords -chemopreventive agents,
SERM, ERpositive breast cancer, dual SERM-SERD scaffolds uterine, cancer risk,
comptutational design,tamoxifen,raloxifene, aromatase inhibitors