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The potential of American ginseng (AG) ( Panax quinquefolium), a commonly used herbal remedy believed to have anticarcinogenic effects, to prevent the development of mammary tumors was evaluated in a mouse model of dimethylbenzanthracene (DMBA)-induced mammary carcinoma. Ginsenosides, believed to be the active components of ginseng and that have a chemical structure similar to estradiol, have previously been shown to possess phytoestrogen-like qualities similar to the soy isoflavone genistein. The effects of AG, administered as powdered root, were compared to the selective estrogen receptor modulators tamoxifen and ospemifene. Eighty-three female SENCAR mice were divided into four treatment groups: control (N = 23), AG (N = 20), ospemifene (N = 20), and tamoxifen (N = 20). American ginseng, ospemifene, and tamoxifen were administered at a dose of 50 mg/kg/day orally by gavage, with the control mice receiving vehicle only. For the first 6 weeks, all mice received 20 microg/day DMBA in combination with their respective treatments. DMBA was then withdrawn, and daily treatments continued for a total of approximately 52 weeks. As expected, ospemifene (p = 0.01) and tamoxifen (p = 0.004) significantly reduced the incidence of mammary tumors compared to the control mice, which had a mammary tumor incidence of approximately 57%. The incidence of mammary carcinomas in the AG group was 40%, a reduction of approximately 29% compared to control. These results suggest that AG may still have the potential to prevent the development of mammary tumors in a chemically induced breast cancer mouse model, although the present study showed no significant difference between control and AG-treated mice.

Ospemifene is a new selective estrogen receptor modulator (SERM) that is being developed for the treatment of urogenital atrophy and osteoporosis. Similarly to other SERMs, ospemifene exhibits antiestrogenic effects in breast tissue, which led to the hypothesis that it may be a potential breast cancer chemopreventive agent. We first assessed the ability of ospemifene, compared to tamoxifen and raloxifene, to prevent dimethylbenzanthracene (DMBA)-induced mammary tumors in female Sencar mice. Ospemifene (N = 18), tamoxifen (N = 20) and raloxifene (N = 17), each dosed at 50 mg/kg, were administered daily by oral gavage, in combination with 20 microg DMBA for the first 6 weeks. Control mice (N = 21) received vehicle plus DMBA only for the first 6 weeks. Daily treatment then continued for 37 weeks. As hypothesized, ospemifene greatly reduced the incidence of mammary carcinomas compared to control mice (p = 0.003), similar to tamoxifen (p = 0.0004); however, in the raloxifene group, no significant effect was seen in mammary tumor prevention (p = 0.20). A follow-up study comparing ospemifene (N = 20) to tamoxifen (N = 20) in the same model was then performed to confirm the results of the first study. The results of the follow-up study, which extended the treatment to 52 weeks, confirmed the results of our previous study, with ospemifene (p = 0.01) and tamoxifen (p = 0.004) significantly decreasing mammary carcinomas compared to controls. The results of these two studies suggest that women taking ospemifene for osteoporosis and/or urogenital atrophy may further benefit from ospemifene's breast cancer chemopreventive effects.

Arzoxifene is a benzothiophene second-generation selective estrogen receptor modulator (SERM) under development by Eli Lilly & Co as a potential treatment for cancer.