Study: A high intake of isoflavons can promote the growth of breast cancer

Shike M, Doane As, Russo L, et al. The effects of a soybean supplement on gene expression in breast cancer: a randomized placebo -controlled study. J National Cancer Institute. 2014; 106 (9). PII: DJU189.

randomized, placebo -controlled study with a period of 7 to 30 days

of the 140 women with breast cancer proven by biopsy, which took part in the study, were evaluated by a total of 132. The participants included premenopausal (39.4 %) and postmenopausal (60.6 %) women with estrogen receptor (er) positive and negative status. The average age was 56.2 years (± 11.9 years).

The participants took up either a soy protein supplement (25.8 g/pkt) or a placebo (milk protein, 25.8 g/pkt) from the time before the surgical resection of each participant (7-30 days). Each pack also contained unknown amounts of maltodextrin, saccharosis, fructose, artificial aromas, calcium phosphate, magnesium phosphate, riboflavin, vitamin a palmitat, folic acid, vitamin D3 and vitamin B12. The concentrations of isoflavons in soy protein were as follows: genistein, 1.8 mg/g soy protein and diadzein, 0.8 mg/g soy protein. The daily doses of isoflavons for those in the intervention group were 98.44 mg/day and 16.51 mg/day of genistine and diadzein.

Primary endpoints were changes in proliferation and apoptosis, measured by immunohistochemistry for ki67 (proliferative index) and Cas3 (apoptotic index) between the two study groups (n = 104; soy, n = 54; placebo, n = 50). The secondary result measurements included changes in gene expression, which were evaluated by nanostring analysis (nanostring technologies, seattle, Washington) between the groups (n = 14; soy, n = 8; placebo, n = 6). The only other secondary result parameters were the entire expression of genes by DNA microarray (n = 51; soy, n = 28; placebo, n = 23) and quantitative PCR (qpcr) (n = 46; soy, n = 27; placebo, n = 19) analyzed from surgical samples (no biopsized fabric). Plasma Isoflavone were measured by most participants at the time of surgical resection (soy, n = 63; placebo, n = 62). The ad hoc analysis included the division of the participants according to plasma genest reflection, which are referred to as "high" (n = 11) and "low" (n = 23) genstein subgroups. The "high" genestine plasmas level was set to 16 ng/ml.

The primary endpoints KI67 and CAS3 did not differ between the intervention group compared to the placebo group or in the ad hoc analysis of patients with highly circulating geni. The nanostring analysis of the gene expression (n = 14) showed a trend towards the variance between groups with several gene groups with opposite directions (over-expressed/underexpressed). There was a large variance of the circulating gene level in the intervention group, with a median value of 6.3 ng/ml and 25 % of the group with circulating mirrors of less than 0.5 ng/ml. For this reason, the authors decided to form a group with a "high" genistine by only in adding the participants with circulating genist reflection above the 95th percentile of the placebo group. When comparing this sub-group with a high genitic content (n = 11) with the subgroup with a low genestine content (n = 23) there was a statistically significant difference ( p <. 01) between the gene signatures in microarray analysis. In addition, the gene signature of the group with a high genitic content showed an overrepresentation of signal paths that regulate cell growth and proliferation ( p <. 001). While the groups were well coordinated without variation of the patient or tumor characteristics, there was a trend for breast cancer of the type Luminal A in the group with low genestine and luminal B in the group with high genestine ( p =. 06). DNA microarray indicated an overexpression of the fibroblast growth factor receptor (FGFR2) and QPCR confirmed a 2.3-fold overexpression of FGFR2 in the soy protein group (n = 27) compared to the placebo (n = 19).

There are persistent debates and contradictory information about soy and breast cancer in literature and even more in the media. This study is interesting, but undoubtedly contributes to confusion. A thorough analysis of the data from this study in connection with the result data on soy aconsum and breast cancer can clarify some of the confusion.

I sometimes emphasize against my patients that when we talk about soy, we speak of "only one bean".

Firstly, very large amounts of soy protein isolate (51.6 g/day) were used in the present study, which contained very high concentrations of genistein (98.44 mg/day) and diadzein (16.51 mg/day). The consumption of almost 100 mg genistine from food sources would be extreme. What was referred to in earlier studies as "diets with high soy acons" did not achieve these values. For example, in the Shanghai Breast Cancer Survival Study, the highest quintile of the recording was less than 15.41 g soy protein and over 62.68 mg overall isoflavone daily. Isoflavone as the highest intake group. ^{2 The current study can be relevant for isoflavons (ie dietary supplements and enriched foods), but it is unlikely that the food quantities, even with high soybean consumers, can reach values ​​examined.}

Another reservation when using this study to inform our general nutritional recommendations is that the study could show no difference in the primary results of proliferation (KI67) or apoptosis (CAS3) between the groups. Only when the intervention group was divided into a subgroup of women (11 in the sojaggruppe vs. 23 in placebo) with a high circulating genistine (> 16 ng/ml), were significant differences in the proliferation signatures via microarray. There was no difference in the original cohort (n = 104).