Breast cancer treatment by the
aromatase inhibitor Letrozole (LET) or
Selective Estrogen Receptor Modulator Tamoxifen (TAM) can result in the onset of menopausal symptoms. Women often try to relieve these symptoms by taking menopausal supplements containing high levels of
phytoestrogens. However, little is known about the potential interaction between these supplements and
breast cancer treatment, especially
aromatase inhibitors. In this study, interaction of
phytoestrogens with the
estrogen receptor alpha and TAM action was determined in an ER-reporter gene assay (BG1Luc4E2 cells) and human breast epithelial
tumor cells (MCF-7). Potential interactions with
aromatase activity and LET were determined in human adrenocorticocarcinoma H295R cells. We also used the previously described H295R/MCF-7 co-culture model to study interactions with steroidogenesis and
tumor cell proliferation. In this model,
genistein (GEN),
8-prenylnaringenin (8PN) and four commercially available menopausal supplements all induced ER-dependent
tumor cell proliferation, which could not be prevented by physiologically relevant LET and 4OH-TAM concentrations. Differences in relative effect potencies between the H295R/MCF-7 co-culture model and ER-activation in BG1Luc4E2 cells, were due to the effects of the
phytoestrogens on steroidogenesis. All tested supplements and GEN induced
aromatase activity, while 8PN was a strong
aromatase inhibitor. Steroidogenic profiles upon GEN and 8PN exposure indicated a strong inhibitory effect on steroidogenesis in H295R cells and H295R/MCF-7 co-cultures. Based on our in vitro data we suggest that menopausal supplement intake during
breast cancer treatment should better be avoided, at least until more certainty regarding the safety of supplemental use in
breast cancer patients can be provided.