Phytoestrogens and breast cancer: a complex story

Abstract

Genistein is an isoflavone with oestrogenic activity that is present in a variety of soy products as a constituent of complex mixtures of bioactive compounds, whose matrix profiles play an important role in determining the overall oestrogenic bioactivity of genistein. We review data on how the profile of soy bioactive compounds can modulate genistein-stimulated oestrogen-dependent tumour growth. Our research has focused on the effects of dietary genistein on the growth of oestrogen (E)-dependent mammary tumours both in vitro and in vivo. Genistein enhances the proliferation of E-dependent human breast cancer tumour growth. In a similar manner, dietary genistein stimulates tumour growth in the chemically-induced (NMU) mammary cancer rodent model. Genistin, the glycoside of genistein, simulates growth similar to that of genistein and withdrawal of either genistein or genistin results in tumour regression. The extent of soy processing modulates the effects of dietary genistein in vivo as soy protein isolate, a highly purified and widely used source of protein that is processed to contain low, medium, and high amounts of isoflavones, stimulate the growth of the E-dependent mammary tumours in a dose dependent manner. In contrast to the more purified diets, studies with soy flour of equivalent genistein levels did not stimulate the growth of E-dependent breast cancer tumours in vivo. However, the size of these tumours also did not regress as is observed in control groups in which oestrogen and genistein have been withdrawn. The expression of the oestrogen-target genes of pS2, progesterone receptor, and cyclin D1 correlates with the growth of E-dependent tumours and has been consistently observed to be induced in response to treatment with dietary genistein. To evaluate whether dietary genistein interacts with current anti-oestrogen breast cancer therapies such as tamoxifen (TAM), we implanted E-dependent tumours into ovariectomized athymic mice and administered oestradiol, oestradiol plus TAM, or oestradiol, TAM, and dietary genistein. In these studies dietary genistein was able to negate the inhibitory effect of TAM on E-stimulated tumour growth. In summary, genistein can act as an oestrogen agonist resulting in proliferation of E-dependent human breast cancer tumours in vivo and its activity can be modulated by the presence of other bioactive components in complex soy foods. Additionally, dietary genistein can negate the inhibitory effects of TAM on E-stimulated growth of MCF-7 cell tumours implanted into ovariectomized athymic mice.

Effect of dietary soy intake on breast cancer risk according to menopause and hormone receptor status

“…However, it is hard to explain the lack of such an inverse association among premenopausal Soy intake and breast cancer YA Cho et al women. One possible explanation is that the stronger protective effect of soy among postmenopausal women may be attributable to their lifestyle rather than to soy intake itself (Helferich et al, 2008). Postmenopausal women may own more traditional lifestyle including a vegetablebased dietary pattern.…”

Post-diagnosis Soy Food Intake and Breast Cancer Survival: A Meta-analysis of Cohort Studies

“…Recent metaanalyses (Qin et al, 2006;Trock et al, 2006;Enderlin et al, 2009;Dong et al, 2011) showed that soy isoflavones intake was associated with a reduced risk of breast cancer incidence. Whereas other studies have shown that isoflavones, the major component of soy, enhance the proliferation of breast cancer cells in vitro (Taylor et al, 2009), promote mammary tumor growth in rats (Helferich et al, 2008), and possibly interfere with the effectiveness of tamoxifen (Schwartz et al, 1998;Ju et al, 2008). As Feng Chi*, Rong Wu, Yue-Can Zeng, Rui Xing, Yang Liu, Zhao-Guo Xu a result, clinicians treating women with breast cancer frequently caution them to either avoid soy foods entirely or use them in moderation (Doyle et al, 2006;Helferich et al, 2008;Velentzis et al, 2008).…”

“…Whereas other studies have shown that isoflavones, the major component of soy, enhance the proliferation of breast cancer cells in vitro (Taylor et al, 2009), promote mammary tumor growth in rats (Helferich et al, 2008), and possibly interfere with the effectiveness of tamoxifen (Schwartz et al, 1998;Ju et al, 2008). As Feng Chi*, Rong Wu, Yue-Can Zeng, Rui Xing, Yang Liu, Zhao-Guo Xu a result, clinicians treating women with breast cancer frequently caution them to either avoid soy foods entirely or use them in moderation (Doyle et al, 2006;Helferich et al, 2008;Velentzis et al, 2008). A cohort study of 1459 Chinese breast cancer patients who commonly eat soy foods prior to cancer diagnosis showed that there were not any association between soy food intake and disease-free breast cancer survival (Boyapati et al, 2005).…”

Positive Effects of Soy Isoflavone Food on Survival of Breast Cancer Patients in China

“…Thus the potential cancerinhibitory effect of soyfood may be found in breast cancers expressing oestrogen receptor. Many epidemiologic studies showed that soy consumption may protect against Ya-Feng Zhang, Hong-Bin Kang*, Bi-Li Li, Rui-Ming Zhang breast cancer, while some experimental studies showed that isoflavones could enhance the proliferation of breast cancer cells in vitro and promote mammary tumor growth in rats ( Helferich et al, 2008;Taylor et al, 2009). However, breast cancer treatments often lead to a decrease in the endogenous estrogen supply of survivors, and a concern has been raised as to whether soy isoflavones may exert their estrogenic effects, promote cancer recurrence, and thus negatively influence overall survival (Helferich et al, 2008;Velentzis et al, 2008).…”