Soy Isoflavone Supplementation for Breast Cancer Risk Reduction: A Randomized Phase II Trial

Department of Surgery, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago IL 60611, USA.
Cancer Prevention Research (Impact Factor: 4.44). 02/2012; 5(2):309-19. DOI: 10.1158/1940-6207.CAPR-11-0251
Source: PubMed


Soy isoflavone consumption may protect against breast cancer development. We conducted a phase IIB trial of soy isoflavone supplementation to examine its effect on breast epithelial proliferation and other biomarkers in the healthy high-risk breast. One hundred and twenty-six consented women underwent a random fine-needle aspiration (rFNA); those with 4,000 or more epithelial cells were randomized to a double-blind 6-month intervention of mixed soy isoflavones (PTIG-2535) or placebo, followed by repeat rFNA. Cells were examined for Ki-67 labeling index and atypia. Expression of 28 genes related to proliferation, apoptosis, and estrogenic effect was measured using quantitative reverse transcriptase PCR. Hormone and protein levels were measured in nipple aspirate fluid (NAF). All statistical tests were two-sided. Ninety-eight women were evaluable for Ki-67 labeling index. In 49 treated women, the median Ki-67 labeling index was 1.18 at entry and 1.12 post intervention, whereas in 49 placebo subjects, it was 0.97 and 0.92 (P for between-group change: 0.32). Menopausal stratification yielded similar results between groups, but within premenopausal soy-treated women, Ki-67 labeling index increased from 1.71 to 2.18 (P = 0.04). We saw no treatment effect on cytologic atypia or NAF parameters. There were significant increases in the expression of 14 of 28 genes within the soy, but not the control group, without significant between-group differences. Plasma genistein values showed excellent compliance. A 6-month intervention of mixed soy isoflavones in healthy, high-risk adult Western women did not reduce breast epithelial proliferation, suggesting a lack of efficacy for breast cancer prevention and a possible adverse effect in premenopausal women.

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    • "Isoflavones have received considerable attention because of their potential to prevent postmenopausal conditions such as cardiovascular disease [6], osteoporosis [7], and hormone-dependent cancers [8]. Daidzein, a major soybean isoflavone, is metabolized to equol in the gastrointestinal tract by intestinal microbiota. "
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    ABSTRACT: Recent studies suggest that some of the clinical effectiveness of soy or daidzein, which is a type of isoflavone, may be attributed to a person's ability to produce equol from daidzein. Equol, which is a metabolite of one of the major soybean isoflavones called daidzein, is produced in the gastrointestinal tract by certain intestinal microbiota where present. Habitual dietary patterns may alter the intestinal bacterial profile, and influence the metabolism of isoflavones and the production of equol. Fructooligosaccharides (FOS) have a prebiotic activity as well as being a dietary fibre. The purpose of the present study was to determine whether FOS supplementation increases equol production in equol producers and stimulates equol production in equol non-producers in Japanese postmenopausal women. A soy challenge was used to assess equol-producer status prior to the start of the study in healthy postmenopausal Japanese women. The study involved 4 separate groups in randomised crossover design. First, subjects were classified as equol producers (n = 25) or non-producers (n = 18), and then they were randomly assigned to the FOS or control group. All subjects received a daily dose of 37 mg isoflavone conjugates in the capsule (21 mg aglycone form) and either FOS (5g/day) or sucrose as control, in a randomised crossover study design. Equol -production was assessed by testing the serum and urine before and after the 2-week supplementation period. The analyses were conducted on 34 subjects completed the study, 21 (61.8%) were classified as equol producers, and 13 (38.2%) as non-producers. Significant differences were observed in the interaction effect of time x equol state after 1 week of intervention (p = 0.006). However there were no effects after 2 weeks of intervention (p = 0.516). Finally, in both equol producers and non-producers, FOS supplementation did not affect the serum equol concentration or the urinary equol to daidzein concentration ratios. We have reported that FOS intervention (5 g/day for 2 weeks) does not significantly modulate the capacity of intestinal microbiota to produce equol in postmenopausal Japanese women, in either equol producers or non-producers in this pilot study. Further larger investigations that explore the roles of specific intestinal microbiota in equol production will enable the establishment of dietary conditions that are required to enhance equol production.
    Full-text · Article · Sep 2013 · Nutrition Journal
    • "Monitoring the expression of 28 genes related to proliferation, apoptosis, and oestrogenic effect, it has been possible to assert that a 6 months intervention of mixed soy isoflavones in healthy, high-risk adult western women did not reduce breast epithelial proliferation, suggesting a lack of efficacy for breast cancer prevention and also a possible adverse effect in premenopausal women [167]. "

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    ABSTRACT: Isolierte Isoflavone werden häufig als Nahrungsergänzungsmittel gegen peri- und postmenopausale Beschwerden angeboten. Diesen aus der Sojapflanze stammenden Pflanzeninhaltsstoffen werden zahlreiche gesundheitliche Effekten nachgesagt wie der Schutz vor Mammakarzinomen, Osteoporose und kardiovaskulären Erkrankungen. Gegenwärtig können jedoch behauptete positive Wirkungen von isolierten Isoflavonen nicht als ausreichend wissenschaftlich belegt angesehen werden. Darüber hinaus wird die Sicherheit dieser Produkte kontrovers diskutiert. Nach Aufnahme hoher Isoflavon-Dosen sind adverse Effekte auf das Brustdrüsengewebe, das Endometrium und die Schilddrüse, Letzteres insbesondere bei bestehendem Jodmangel, nicht auszuschließen. Isoflavone können durch östrogene Effekte möglicherweise einen stimulierenden Einfluss auf bestehende Östrogen-sensitive maligne Zellen aufweisen. Im Fokus der Risikobetrachtung stehen hierbei insbesondere Frauen in und nach der Menopause, da diese die Zielgruppe für Isoflavon-Präparate sind und sie ohnehin ein erhöhtes Brustkrebsrisiko besitzen. Eine längerfristige Gabe von isolierten Isoflavonen insbesondere in höheren Dosierungen ist kritisch zu sehen und sollte zumindest erst nach Aufklärung der Patienten und nicht ohne ärztliche Kontrolle erfolgen.
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