Effects of soy-derived isoflavones and a high-fat diet on spontaneous mammary tumor development in Tg.NK (MMTV/c-neu) mice

Mirjam Luijten, Anni Rønfeldt Thomsen, Jolanda A.H. Van Den Berg, Piet W. Wester, Aart Verhoef, Nico J.D. Nagelkerke, Herman Adlercreutz, Henk J. Van Kranen, Aldert H. Piersma, Ilona K. Sørensen, Ghanta N. Rao, Coen F. Van Kreijl

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)


Phytoestrogens such as isoflavonoids and lignans have been postulated as breast cancer protective constituents in soy and whole-grain cereals. We investigated the ability of isoflavones (IFs) and flaxseed to modulate spontaneous mammary tumor development in female heterozygous Tg.NK (MMTV/c-neu) mice. Two different exposure protocols were applied, either from 4 wk of age onward (postweaning) or during gestation and lactation (perinatal). In the post-weaning exposure study, mice were fed IFs or flaxseed in a high-fat diet. In addition, flaxseed in a low-fat diet was tested. Postweaning exposure to IFs and flaxseed tended to accelerate the onset of mammary adenocarcinoma development, although tumor burden at necropsy was not changed significantly. Perinatal IF exposure resulted in enhanced mammary gland differentiation, but palpable mammary tumor onset was not affected. However, tumor burden at necropsy in the perinatal exposure study was significantly increased in the medium- and high-IF dose groups. Comparison of both exposure scenarios revealed a strongly accelerated onset of tumor growth after perinatal high-fat diet exposure compared with the low-fat diet. This study shows that breast cancer-modulating effects of phytoestrogens are dependent both on the background diet and on the timing of exposure in the life cycle.

Original languageEnglish
Pages (from-to)46-54
Number of pages9
JournalNutrition and Cancer
Issue number1
Publication statusPublished - 2004
Externally publishedYes

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Oncology
  • Nutrition and Dietetics
  • Cancer Research


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