IntroductionBreast cancer is one of the most common types of cancer in women and 70% of breast cancers are caused by overexpression of the estrogen receptor (ER). ER represents a viable and important pharmaceutical target against cancer. It is targeted by pharmaceutical agents for hormone replacement in postmenopausal women and reproductive cancers such as prostate cancer, uterine cancer, and breast cancer [1]. ERs are classified into two types, ER alpha and ER beta which belong to the nuclear receptor super family. ER alpha and ER beta have similar but not identical structures. Upregulation of ER alpha causes cell proliferation, inhibition of apoptosis, stimulation of invasion and metastasis, and promotion of angiogenesis. Although little is known about ER beta, its function is thought to be distinct from ER alpha and likely has opposing activity on tumor growth [2]. Tamoxifen is the medication regularly prescribed for the treatment of breast cancer. The anti-cancer property of Tamoxifen has been attributed to its anti-estrogenic properties. The use of tamoxifen is limited due to acquired resistance to tamoxifen in many cancer patients [3]. Nonsteroidal anti-inflammatory drugs (NSAIDs) are medications that have anti-inflammatory action and are also used to treat fever (antipyretic) and reduce pain. Aspirin was the first NSAID used to treat human diseases. It is derived from the bark of the willow tree. NSAIDs act as non-selective inhibitors of the enzyme cyclooxygenase (COX), causing a reduction in the formation of prostaglandin and thromboxane. NSAIDs have recently received increasing attention as anticancer agents. In vivo studies with NSAIDs have shown the anticancer property of these drugs against breast...... middle of article ......han ArgusDock [14-15].ConclusionMolecular docking was used to explore the binding mechanism and to correlate the docking score of NSAIDs with human estrogen receptor alpha (PDB ID: 3ERT) and estrogen-related receptor gamma (PDB ID: 2GPU). In the present study, the results show that NSAIDs have good binding energy values ​​with both ER proteins. Valdecoxib, withdrawn from the market, showed the good energy values ​​of optimized NSAIDs. The antagonistic action of NSAIDs against the ER could be one of the possible reasons why NSAIDs have anticancer properties; further studies need to be carried out to confirm these properties. The result of our study can be used for the development of NSAIDs as potential estrogen receptor inhibitors. Acknowledgments This research is conducted independently, no funding was received to carry out this work..