New targets to reverse tamoxifen resistance is of crucial importance. CCNA2 belongs to the highly conserved cyclin family and is expressed in almost all tissues in human body. It plays critical roles in the control of cell cycle at the G1/S and the G2/M transitions and is essential in embryonic cells and in the hematopoietic lineage. Data from Human Protein Atlas show that CCNA2 is overexpressed in dozens of cancer types, which indicates its potential roles in cancer transformation and progression. It is also reported that CCNA2 may be involved in the processes of epithelial-mesenchymal transitions and metastasis. Nevertheless, the prognostic power of CCNA2 in ER+ Isoacteoside breast cancer and its relation with tamoxifen resistance have never been reported before. In this study, we 
explored the possibility of CCNA2 as a Isochlorogenic-acid-C biomarker for the prognosis of ER+ breast cancer patients and prediction of tamoxifen efficacy. Besides, an interaction network was constructed to show how CCNA2 and available anti-cancer drugs could interaction with each other. Among all the datasets used in this study, GSE47561, GSE3494, GSE33366 and GSE26459 are obtained from Gene Expression Omnibus dataset; van dataset and Gyorffy dataset were obtained from supplementary data of previous publications. For all the study subjects in this research, ER positivity was defined as greater than 10 fmol/mg tumor tissue and greater than 1% nuclear staining or immunohistochemistry score of at least 3 for the biochemical and immunohistochemical assays, respectively. Unfortunately, a subset of patients who received adjuvant tamoxifen would eventually experience relapse and die as a result of the disease, 30% of ER+ tumors were not prevented by tamoxifen in National Surgical Adjuvant Breast and Bowel Project prevention trial. Numerous studies have been performed, which combined endocrine therapy with agents that could modulate these mechanisms, so as to prevent the occurrence of tamoxifen resistance. Due to the pressing clinical need, several other investigators have developed gene predictors that c predict outcome in ER+ breast cancer treated with adjuvant tamoxifen therapy. For instance, Cyclin D1, Acid ceramidase 1and p53 accumulation had been reported that could predict outcome in ER+ breast cancer treated with adjuvant anti-estrogen therapy. Likewise, Retinoic acid receptor alpha, CD44 and deltaEF1 had been reported to be involved in the development of tamoxifen resistance in breast cancer.. It have been reported that breast stem cells and Wnt signaling activation may be the mechanism of resistance to tamoxifen. CCNA2, a key regulator of cell cycle, is overexpressed in many human cancers, including breast cancer. However, the association between CCNA2 overexpression and tamoxifen resistance in ER+ breast cancer remains unclear. Our results show the significant prognostic power of CCNA2 in ER+ breast cancer progression and tamoxifen resistance. Importantly, high level of CCNA2 is correlated with tamoxifen treatment failure and poor DMFS. We might be able to stratify ER+ breast cancer patients by testing the mRNA expression level of CCNA2and decide when and how to use tamoxifen treatment in combination with appropriate therapeutic.