Soy isoflavones increase latency of spontaneous mammary tumors in mice

Soy protein, with and without isoflavones, is being added to foods by manufacturers in response to the Food and Drug Administration (FDA)-approved health claim for cardiovascular protection. Furthermore, soy isoflavones are increasingly consumed by women in the United States as an alternative to hormone replacement therapy. The role of these phytoestrogens in breast cancer is controversial. Although exposure of rodents to soy isoflavones during the perinatal period appears to reduce mammary cancer formation, exposure in utero or during adulthood may increase tumor growth. The mouse mammary tumor virus (MMTV)-neu mouse spontaneously develops mammary tumors due to overexpression of the ErbB-2/neu/HER2 oncogene. This model is comparable with human breast cancer because overexpression of the neu oncogene occurs in 20-40% of human breast cancers. We fed MMTV-neu mice AIN-93G diets containing no isoflavones, 250 mg/kg genistein, 250 mg/kg daidzein or an isoflavone mixture (NovaSoy, equivalent to 250 mg genistein/kg) from 7 wk of age. Mammary tumor latency was significantly delayed in mice fed isoflavones compared with the control. Once tumors formed, however, the isoflavones did not reduce the number or size of tumors such that at 34 wk of age there were no differences in tumor burden among the treatment groups. Hence, in the MMTV-neu mouse, soy isoflavones delayed mammary tumorigenesis. Further studies are warranted to define the cellular mechanisms through which these compounds affect mammary tumorigenesis in this model.