Potential mechanisms whereby the lignan or oil components of flaxseed, alone or in combination with tamoxifen exert their effect on breast cancer

Many women with breast cancer, some being treated with the drug tamoxifen (TAM), consume phytoestrogen (PE)–rich foods as complementary therapies. Flaxseed (FS), an oilseed with high amounts of PE lignan (secoisolariciresinol diglucoside, SDG) and n‐3 fatty acid–rich oil (FO), can inhibit breast tumor growth and increase the effectiveness of tamoxifen (TAM). Our objective was to elucidate the mechanisms whereby the FS components (SDG or FO), alone (experiment 1) or with TAM (experiment 2) exert their effect. Ovariectomized athymic mice with established human breast tumors (MCF‐7) were treated for 8 weeks with basal diet (BD, control) or BD+10%FS, SDG, FO, or SDG+FO (SDG and FO at levels in 10% FS). Palpable tumors regressed faster (p≤0.05) and had lower proliferation (p≤0.05) in all treatment groups than control. FS and SDG increased apoptosis (p≤0.05) and decreased (p≤0.05) Bcl2, pS2, IGF‐1R, cyclin D1 (CD1), HER2 and EGFR mRNA expressions. TAM‐treated tumors were larger (p≤0.05) and had higher (p≤0.05) proliferation and CD1, Bcl2, IGF‐1R, HER2, EGFR mRNA expressions and lower apoptosis (p≤0.05) than control, which were modulated by all treatments but more so by FO. In conclusion, the more active FS component is SDG without TAM, and FO with TAM. They reduced cell proliferation and increased apoptosis through modulation of the estrogen receptor and growth factor receptor signaling pathways.