Soy and Tamoxifen Don’t Mix
Jacob Schor ND FABNO
March 30, 2009

Soy is great stuff for cancer prevention. It prevents carcinogens from causing cancer. [1] In some situations it appears useful during cancer treatment. It sensitizes cancer cells to certain chemo drugs making it more likely they will die from treatment. [2] As useful as all this sounds, soy does not appear to mix well with tamoxifen.

In a paper published in Cancer Research back in 2002, researchers reported on an experiment in which they examined the response of tumors to estrogen in combination with tamoxifen and the soy extract genistein.

This is important research because many women who have been treated or are being treated for breast cancer read or hear that soy is good for them. In our practice more and more women tell us they are purposefully eating soy products or taking soy based supplements because they have heard it protects against breast cancer. Whether it does or doesn’t is a complex and debated issue that I am not going to attempt to answer here.

The researchers in this study looked at the interaction between the soy isoflavone
genistein, and the drug tamoxifen (TAM), on the growth of estrogen dependent breast cancer cells implanted in mice that had their ovaries removed. Giving the mice estrogen stimulated tumor growth. Treating the mice with tamoxifen suppressed the breast tumor growth. There’s nothing surprising there. This is why for the last 4 decades women with estrogen dependent breast cancer have been treated with tamoxifen. Feeding the mice genistein ‘negated’ the inhibitory effect of tamoxifen on the breast cancer tumors. [3]

This suggests that women taking tamoxifen should avoid soy products.

Multi-targeted therapy of cancer by genistein.

Cancer Lett. 2008 Oct 8;269(2):226-42. PMID: 18492603.

Soy isoflavones have been identified as dietary components having an important role in reducing the incidence of breast and prostate cancers in Asian countries. Genistein, the predominant isoflavone found in soy products, has been shown to inhibit the carcinogenesis in animal models. There is a growing body of experimental evidence showing that the inhibition of human cancer cell growth by genistein is mediated via the modulation of genes that are related to the control of cell cycle and apoptosis. It has been shown that genistein inhibits the activation of NF-kappaB and Akt signaling pathways, both of which are known to maintain a homeostatic balance between cell survival and apoptosis. Moreover, genistein antagonizes estrogen- and androgen-mediated signaling pathways in the processes of carcinogenesis. Furthermore, genistein has been found to have antioxidant properties, and shown to be a potent inhibitor of angiogenesis and metastasis. Taken together, both in vivo and in vitro
studies have clearly shown that genistein, one of the major soy isoflavones is a promising agent for cancer chemoprevention and further suggest that it could be an adjunct to cancer therapy by virtue of its effects on reversing radioresistance and chemoresistance. In this review, we attempt to provide evidence for these preventive and therapeutic effects of genistein in a succinct manner highlighting comprehensive state-of-the-art knowledge regarding its multi-targeted biological and molecular effects in cancer cells.
PMCID: PMC2575691 [Available on 2009/10/08]

The role of genistein and synthetic derivatives of isoflavone in cancer prevention and therapy.

Mini Rev Med Chem. 2006 Apr;6(4):401-7. PMID: 16613577

Genistein, one of the predominant soy isoflavones, has been shown to compete with 17beta-estradiol for estrogen receptor binding because of its structural similarity, resulting in agonistic or antagonistic activity. It causes inhibition of cell growth in breast and prostate cancers in vivo and in vitro. From gene expression profiles, genistein has been found to regulate the genes that are critical for the control of cell proliferation, cell cycle, apoptosis, oncogenesis, transcription regulation, and cell signal transduction pathways. It has been reported that genistein induces apoptosis and inhibits activation of NF-kappaB and Akt signaling pathways, both of which are known to maintain a balance between cell survival and apoptosis. Recently, we found that genistein sensitized cancer cells to apoptosis induced by chemotherapeutic agents including docetaxel, gemcitabine and cisplatin through inactivation of NF-kappaB in multiple cancer cell lines. To enhance the anti-cancer activity
of
genistein, we have synthesized structurally-modified derivatives of isoflavone based on the structural requirements for optimal anti-cancer effect. We found that these synthetic derivatives of isoflavone exerted higher anti-cancer activity with lower IC50. These derivatives of isoflavone also induced more apoptosis compared to genistein. These results suggest that genistein and synthetic structurally-modified derivatives of isoflavone may be promising agents for cancer chemoprevention and therapy either alone or in combination with existing chemotherapeutic agents.
PMID: 16613577


Dietary genistein negates the inhibitory effect of tamoxifen on growth of estrogen-dependent human breast cancer (MCF-7) cells implanted in athymic mice.

Cancer Res. 2002 May 1;62(9):2474-7. PMID: 11980635

The use of dietary isoflavone supplements by postmenopausal women with breast cancer is increasing. We investigated interactions between the soy isoflavone, genistein, and an antiestrogen, tamoxifen (TAM), on the growth of estrogen (E)-dependent breast cancer (MCF-7) cells implanted in ovariectomized athymic mice. We hypothesized that weakly estrogenic genistein negate/overwhelm the inhibitory effect of TAM on the growth of E-dependent breast tumors. Six treatment groups were used: control (C); 0.25 mg estradiol (E2) implant (E); E2 implant + 2.5 mg TAM implant (2.5 TE); E2 implant + 2.5 mg TAM implant + 1000 ppm genistein (2.5 TEG); E2 implant + 5 mg TAM implant (5 TE), and E2 implant +5 mg TAM implant +1000 ppm genistein (5 TEG). Treatment with TAM (2.5 TE and 5 TE) suppressed E2-stimulated MCF-7 tumor growth in ovariectomized athymic mice. Dietary genistein negated/overwhelmed the inhibitory effect of TAM on MCF-7 tumor growth, lowered E2 level in plasma, and increased expression
of E-responsive genes (e.g., pS2, PR, and cyclin D1). Therefore, caution is warranted for postmenopausal women consuming dietary genistein while on TAM therapy for E-responsive breast cancer.
PMID: 11980635