Purpose of investigation: The pleiotropic factor Y-box binding protein-1 (YB-1) is clinically correlated with breast cancer patients’ poor outcome. Due to the intereference of YB-1 with the estrogen receptor, the authors examined the antiproliferative efficacy of 4-hydroxytamoxifen (4-OHT) and fulvestrant (FUL) in the presence of low and high levels of YB-1. Materials and Methods: The human breast cancer cell line MCF-7 was transfected to overexpress YB-1 protein. 4-OHT and FUL incubation experiments were performed and cell growth behaviour of YB-1 overexpressing MCF-7 cells were compared to unmodified MCF-7 cells expressing endogenous YB-1 levels. Results: The incubation of MCF-7 cells with 100 nM 4-OHT and 1 nM FUL over a period of 120 hours clearly demonstrated the antiproliferative properties of both antiestrogens as expected. Notably, high levels of YB-1 led to an increase of antiproliferative properties in the presence of 4-OHT and FUL. Conclusion: The data presented here demonstrated YB-1 enhances the antiestrogenic efficacy of 4-OHT and FUL. Thus, the group of high level YB-1 mamma carcinoma patients might increasingly benefit from endocrine therapy.