Phytoestrogens and breast cancer

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Abstract

The role of phytoestrogens and consumption of phytoestrogen-rich foods such as soy containing isoflavones and whole grain products with lignans for the prevention of breast cancer is reviewed. It is concluded that soy-containing diet in adult women is not or only slightly protective with regard to breast cancer, but that it may be beneficial if consumed in early life before puberty or during adolescence supporting results of immigrant and epidemiological studies. No negative effects of soy on breast cancer have been observed. On the other hand, a diet low in lignans, resulting in a low plasma enterolactone concentration, increases risk both in a case-control and a prospective study, but some controversial results have also been obtained. Some of these results may be explained by the fact that the determinants of plasma or urinary enterolactone concentration are very different in different countries. In Scandinavia, the main determinants are whole grain cereal food, vegetables and berries. Whether the protective effect is caused by the phytoestrogens in the diet or whether they are only biomarkers of a healthy diet has not been established.

Introduction

Already in the early 1980s it was suggested that lignans and isoflavonoids may prevent breast cancer and this has led to numerous epidemiological, experimental, case-control and prospective studies to evaluate this hypothesis. The literature, except for the most recent publications, has been reviewed in [1], [2]. A more recent discussion on the use of phytoestrogens in breast cancer survivors contains important information also with regard to the phytoestrogens or soy, and breast cancer [3].

Section snippets

Epidemiology of phytoestrogens

Soybean products are staple food in many Asian countries like in Japan, China, Korea and Indonesia. These countries had until recently a very low incidence of cancer and coronary heart disease, but the incidence is steadily increasing, particularly in Japan, due to change in dietary habits and life style [4]. In these countries, however, the diet is low in fat and red meat and often rich in fish (Vitamin D!) being a dietary pattern also believed to decrease cancer risk. It must be kept in mind

Experimental soy or isoflavone studies in rodents and with cell cultures

Experimental studies in rodents on the effect of soy products on mammary cancer were recently comprehensively summarized [23]. The conclusion was that in the studies with statistical treatment of the results no significant preventive effects were observed. The same was true in one recent study [24], and in one of them a stimulating effect of genistein on DMBA-induced mammary adenocarcinoma was shown in wild type but not in ERαKO mice [25]. In a third study there was a slower growth of the

Human studies with soy or isoflavones

The publications dealing with the possible association between phytoestrogens or phytoestrogen-rich diet and breast cancer risk in women are shown in Table 1 available on the website http//oncology.thelancet.com, and including the references [7]. There is some evidence for a protective effect of a diet containing soybean products. In some populations the soy consumption was very low and may definitely not give the true picture of the situation. The large prospective study by Key et al. [8] in

Negative effects of soy isoflavones on the breast

There is evidence that high endogenous estrogen level prenatally may increase breast cancer risk in women [42], [43] and there is some experimental support in rats for the view that phytoestrogens may negatively affect breast cells during pregnancy. However, in the experimental study in rats [43] parenteral administration of genistein was employed which has a much stronger effect than oral dosage. Both in newborn Japanese children and in their mothers at birth high levels of phytoestrogens are

Lignans and breast cancer

In very early studies in the 1980s following for a whole year small groups of omnivorous and vegetarian women as well as healthy breast cancer patients after surgical removal of small breast tumors, a tendency to lower excretion of lignans in urine of the breast cancer patients was found, which was significant or almost significant compared to the vegetarians (reviews in [1], [2]). The low urinary excretion of enterolactone in breast cancer was confirmed in an Australian material [20]. Grain

Possible mechanisms of phytoestrogen action in the breast

The possible favorable effects of the phytoestrogens on breast cancer may be mediated via many different mechanisms and some of them have been discussed above. In a situation when we do not even know whether the effect of soy or unrefined cereal products are due to their content of phytoestrogens a causal relationship with disease prevention is hypothetical. One mechanism may involve ERβ and its various isoforms, e.g. by ERβ forming heterodimers with ERα reducing estrogen effects [66]. The

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    Proceedings of the 15th International Symposium of the Journal of Steroid Biochemistry and Molecular Biology, “Recent Advances in Steroid Biochemistry and Molecular Biology”, Munich, Germany, 17–20 May 2002.

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