No clear result regarding protective effects of isoflavones was found in a review of case-control and prospective studies (Gikas and Mokbel 2005). A major problem with studies aimed on the detection of protective effects is that Asian women examined in the trials usually have a rather high life-long exposure to isoflavones. Under such conditions subtle differences in exposure may not be easily detected. The effect is, however, real and has been demonstrated in a meta-analysis of case-control studies (Trock et al. 2006): High soy intake was associated with a modest reduction of breast cancer risk. A similar result was found in a meta-analysis of epidemiological studies (Qin et al. 2006). Isoflavone intake is associated with a 20 % risk reduction of breast cancer. This effect size may not be very high, but it is still noticeable, and the socioeconomic and health benefit is undeniable.
The cancer-protective effect of isoflavone exposure may last rather long: in a review of clinical data a significant reduction of breast cancer incidence among past isoflavone users was found (Tempfer et al. 2007).
Isoflavones taken at dietary levels (i.e., 50-100 mg/day) do not appear to promote breast cell proliferation in healthy women and breast cancer survivors, as analyzed in a review (Messina and Wood 2008). Conclusions drawn earlier by the German Senate Commission for the health-related assessment of Food (Senatskommission für die gesundheitliche Bewertung von Lebensmitteln, SKLM) related to potential cancer-promoting risks are not backed by literature data (Messina 2008).
Another review of the literature (Steiner et al. 2008) listed epidemiological evidence and pre-clinical data which strongly support a correlation between soy isoflavone consumption and protection from breast cancer. This protection from breast cancer is obviously most pronounced when exposure to isoflavones happens in youth and adulthood. A review of epidemiological studies points to the reduction of breast cancer risk by isoflavone exposure, although animal studies might suggest the contrary (Tomar and Shiao 2008).
A meta-analysis of cohort and case-control studies in Asian and Western women (Wu et al. 2008) resulted in a significant trend of decreasing breast cancer risk with increasing soy intake. Best effects were achieved with ≥ 20 mg of isoflavones/day in Asian women, whereas in European women with low isoflavone intake the effect could not be demonstrated. Lower intake by Asian women also correlates with a lower level of protection: At very low intakes no protective effect can be observed.
A recent systematic meta-analysis of clinical trials with measurements of hormonal levels under the impact of isoflavones observed a non-significant increase of serum estradiol, accompanied by a likewise non-significant decrease of serum estrone levels (Hooper et al. 2009). Estrone is considered to have a higher carcinogenicity than estradiol. The results may therefore be interpreted as an improved level of safety with regard to hormone-induced breast cancer provided by an increased supply of isoflavones.
In conclusion, the reviews and meta-analyses regularly conclude on a potential reduction of breast cancer incidence through exposure to isoflavones, even in women with a high individual risk. In contrast, none of the reviews and meta-analyses of clinical data has concluded on an increased risk of breast cancer by isoflavone exposure.
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Hormonal safety parameters in clinical trials studying estrogenic effects of isoflavones
Safety 