Due to the estrogenic properties of soy-derived
isoflavones, many postmenopausal women are using these compounds as a natural alternative to
hormone replacement therapy (HRT). How
isoflavones impact
breast cancer in postmenopausal women is important, because a majority of
breast cancer cases occur in this age group. Chemical induction of mammary
tumors in female rats has been used to determine that exposure of the mammary gland to soy
isoflavones prior to
tumor induction is protective against
tumor formation. Here we investigate the effect of dietary
genistein on mammary
tumors that have already formed. The study was designed to determine the action of dietary
genistein in a low endogenous
estrogen environment as is observed in postmenopausal women. Animals were ovariectomized (OVX) after mammary
tumor development and were then placed into one of three treatment groups: positive-control (OVX+
estradiol implant),
genistein (OVX+ 750 p.p.m.
genistein) and negative-control (OVX alone).
Tumors were distinguished as malignant or benign by histopathological examination and were further characterized as either
estrogen-dependent or
estrogen-independent using immunohistochemistry to identify the presence of both
estrogen receptor (ER) alpha and the
progesterone receptor (PR).
Genistein at 750 p.p.m. increased the weight of
estrogen-dependent
adenocarcinomas in ovariectomized rats compared with the negative-control animals.
Genistein treatment also resulted in a higher percentage of proliferative cells in
tumors and increased uterine weights when compared with negative-control animals. Collectively, these effects are probably due to the estrogenic activity of
genistein. Plasma
genistein concentrations in animals fed the
isoflavone-containing diet were at physiological levels relevant to human exposure.
Estradiol concentrations in ovariectomized animals not receiving an
estradiol supplement were similar to those observed in postmenopausal women. The data suggest that in an endogenous
estrogen environment similar to that of a postmenopausal woman, dietary
genistein can stimulate the growth of a mammary
carcinogen MNU-induced
estrogen-dependent mammary
tumors.