Abstract: Objective :To investigate the mechanism of interaction between the ERβ and MAPKsignal transduction pathways in the course of breast cancer development. Methods :Twenty-four micewere randomly divided into the control group,the TAM group, the CTX group or the combination group.Immunohistochemical staining was used to detect the expression level of ERβ, MEK-2 and p-ERK inbreast cancer cells after the administration of TAM and CTX. Flow cytometry (FCM) was used to detectchanges in cell cycle and the apoptotic index. Cell morphology was observed to detect transformation. Results :Both TAM and CTX inhibited tumor growth, especially in the CTX group and the combinationgroup (F=14.554, P<0.05). In comparison with the control group, the other groups showed inhibition oftumor cell proliferation and a decreased percentage of cancer cells in S phase (P<0.05). FCM datashowed the apoptotic peak was to the left of G 0 phase in the TAM group and the combination group.The apoptotic rate was 2.3% in the TAM group and 13.1% in the combination group (P<0.05). Tumorcells grew actively in the control group and karyokinesis was observed. Cancer cells showed variouslevels of focal necrosis in the experimental groups and the cell nuclei underwent swelling, cavitations,and karyopyknosis. Nuclear fragmentation and apoptotic bodies could be observed, especially in thecombination group. Both TAM and CTX significantly inhibited the expression of ERβ, MEK-2 and p-ERK in breast cancer cells (F=211.88, 179.08, 156.44,P<0.05). The expression of these three proteinsdemonstrated synergistic actions. Conclusion :We demonstrate that the ERβand MAPK signal trans-duction pathways interact and can influence cancer development, apoptosis and endocrine therapy re-sistance. These proteins may become new targets of endocrine and chemical therapies for breast cancer.