Study summary: The current study was designed to assess the influence of the phytoestrogens genistein and apigenin on breast cancer growth. Genistein and apigenin are present in several commercial supplements designed to be used for postmenopausal symptoms and breast health. Both flavonoids were found to stimulate proliferation of estrogen receptor-positive/progesterone receptor-positive (ER+/PR+) MCF-7 and estrogen receptor alpha (ERα-positive) T47D breast cancer cells. However, the compounds did not stimulate the proliferation of ERα-negative MDA-MB-435 breast cancer cells. Genistein was observed to be more efficient in this regard due to its higher binding affinity for ERα. Similarly to actions previously described for estradiol (E2), both genistein and apigenin were found to down regulate ERα and enhance estrogen response element-dependent gene expression. An additional finding that genistein antagonizes the anti-proliferative effect of hydroxytamoxifen indicates that certain phytoestrogens may be detrimental for women with breast cancer who are being treated with tamoxifen. The authors conclude that because of their ability to stimulate breast cell growth, the use of phytoestrogen supplements in postmenopausal women could be detrimental.