title: Low-dose dietary phytoestrogen abrogates tamoxifen-associated mammary tumor prevention.
abstract: Wild-type erbB-2/neu transgenic mice were used to study the interactions between tamoxifen and dietary phytoestrogens (or isoflavones) by dose and form in vivo. Mice were randomized to one of four dietary formulas and implanted with an 8-week continuous-release tamoxifen or placebo pellet at 8 weeks of age. In placebo-treated mice, soy meal diet (but not diets supplemented with low-dose or high-dose isoflavones or a casein diet) resulted in prolongation of tumor latency. In tamoxifen-treated mice fed the soy meal, casein, or high-dose isoflavone enriched diets, the majority (>80%) showed no tumor formation by 60 weeks of age. Of the mice that developed tumors, latency was significantly prolonged. In tamoxifen-treated mice fed the low-dose isoflavone enriched diet, a much higher rate of mammary tumor development (>50%; P < 0.002) and a shorter tumor latency were observed. In vitro studies of human and mouse mammary tumor cell lines confirm that low doses of genistein, co-administered with tamoxifen, promote cell proliferation. This is in contrast to tamoxifen alone or tamoxifen with higher doses of genistein that are growth inhibitory. In summary, low-dose dietary isoflavones abrogated tamoxifen-associated mammary tumor prevention in vivo. These interactions are supported by in vitro data from human and mouse mammary tumor cell lines. These dose-associated interactions likely have relevance to the human use of tamoxifen for prevention or treatment of breast cancer.
authors.affiliation: Department of Pathology, University of Oklahoma Health Sciences Center, 940 Stanton L. Young Boulevard, Oklahoma City, OK 73104, USA.
authors.forename: Bolin
authors.initials: B
authors.lastname: Liu
authors.forename: Susan
authors.initials: S
authors.lastname: Edgerton
authors.forename: Xiaohe
authors.initials: X
authors.lastname: Yang
authors.forename: Aeree
authors.initials: A
authors.lastname: Kim
authors.forename: Dalia
authors.initials: D
authors.lastname: Ordonez-Ercan
authors.forename: Terza
authors.initials: T
authors.lastname: Mason
authors.forename: Kathy
authors.initials: K
authors.lastname: Alvarez
authors.forename: Christine
authors.initials: C
authors.lastname: McKimmey
authors.forename: Naxin
authors.initials: N
authors.lastname: Liu
authors.forename: Ann
authors.initials: A
authors.lastname: Thor
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000517:prevention & control*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007529:Isoflavones / Q000009:adverse effects / Q000494:pharmacology; D008325:Mammary Neoplasms, Experimental / Q000517:prevention & control*; D051379:Mice; D008822:Mice, Transgenic; D048789:Phytoestrogens / Q000009:adverse effects / Q000494:pharmacology*; D013629:Tamoxifen / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: D007529:Isoflavones; D048789:Phytoestrogens; D013629:Tamoxifen