This study aims to gain a better understanding of therelationship between CCN5 and ER-α in normal and cancer cells, the molecularbasis of restoring ER-α by CCN5 in TNBC cells, and finally, the efficacy oftamoxifen (Tam) in TNBC cells by combination treatment of Tam and human recombinantCCN5 (hrCCN5) protein using rational in vitro and in vivomodels. This evidence concerns the gene CCN5 and cancer.