Avemar, a fermented wheat germ extract, has been applied in the supplementary therapy of human cancers. Because tamoxifen is commonly used in the therapy of ER+ breast cancer, in this study the combined effect of tamoxifen and Avemar treatment was investigated on MCF-7 breast cancer cells, in order to detect a possible agonistic or antagonistic action. Cytotoxicity was measured by MTT assay, the percentage of mitoses and apoptotic cells was determined morphologically, apoptosis and S-phase was measured by flow cytometry, and estrogen-receptor activity was determined by semiquantitative measurement of the estrogen-responsive pS2 gene mRNA production. Tamoxifen (1 nM) alone had no effect on the percentage of the apoptotic cell fraction and significantly reduced the percentage of the S-phase, compared to untreated cells. Avemar (625 microg/mL) significantly increased apoptosis after 48 hours of treatment. Tamoxifen together with Avemar significantly increased apoptosis already 24 hours after starting treatment but had only a slight (not significant) effect on mitosis and S-phase. Estrogen-receptor activity of MCF-7 cells was enhanced by Avemar, decreased by tamoxifen, and was further decreased by combined tamoxifen and Avemar treatment. As apoptosis increased when Avemar was added to tamoxifen treatment, the use of supplementary therapy with Avemar in the case of ER+ breast tumors may enhance the therapeutic effects of tamoxifen.