Straight Talk About Soy and Breast cancer
Phytoestrogens don’t always mimic estrogen. In some tissues and in some people, they may block the action of estrogen. If soy’s estrogen-blocking action occurs in the breast, then eating soy could, in theory, reduce the risk of breast cancer because estrogen stimulates the growth and multiplication of breast and breast cancer cells. Studies so far have not provided a clear answer. Some have shown a benefit with soy consumption and breast cancer while others show no association. [14-17] It appears that the effects of soy may vary depending on menopausal status, the age at which soy is consumed, and type of breast cancer.
In animal and cell studies, high dosages of isoflavone or isolated soy protein extracts tend to stimulate breast cancer growth. [18,19] However, studies that observe people consuming soy foods over time show either a protective or neutral effect. Women from Asian countries appear to receive greater protective benefit from breast cancer with high soy intakes than American and European women, but this may simply be a difference in the amount of soy consumed. [20,21] Asian women may have higher levels of equol, a substance metabolized from the isoflavone daidzein by bacterial flora in the intestines.  Equol is believed to block potentially negative effects of human estrogen, but not all women possess the bacteria needed to create equol.  It is estimated that 30-50% of all humans are able to produce equol.  Eating soy foods starting at an early age (such as those found in many traditional Far East Asian diets) may be why women from some countries find greater benefit from soy foods than others.  However, the overall evidence on equol and cancer risk is unsettled. 
The Shanghai Women’s Health Study which followed 73,223 Chinese women for more than 7 years has been the largest and most detailed study of soy and breast cancer risk in a population with high soy consumption.  In this study, women who ate the most soy had a 59% lower risk of premenopausal breast cancer compared with those who ate the lowest amounts of soy. There was no association with postmenopausal breast cancer. Risk was 43% lower when soy was eaten during adolescence. Seven years later, the study authors published a follow-up analysis from the same cohort over 13 years to evaluate any association between soy foods and specific types of breast cancer defined by hormone receptors and by menopausal status (Estrogen [ER] +/-; Progesterone [PR] +/-).  Key highlights of the study:
- A 22% lower risk of breast cancer when comparing the highest to lowest intakes of soy during adulthood.
- A 28% lower risk of hormone positive (ER+, PR+) breast cancer in postmenopausal women.
- A 54% lower risk of hormone negative (ER-, PR-) breast cancer in premenopausal women.
- A 47% lower risk of premenopausal breast cancer when comparing high to low intakes of soy during adolescence and adulthood.
The Breast Cancer Family Registry was a prospective study following 6,235 women for 9 years diagnosed with breast cancer and living in the U.S. and Canada; intake of soy isoflavones was examined in relation to deaths from all causes.  Key highlights of the study:
- Women who ate the highest amounts of soy isoflavones had a 21% lower risk of death compared with women with the lowest intakes.
- Women who had ER-/PR- tumors and who were not receiving tamoxifen appeared to receive greatest benefit from the higher soy isoflavone intakes. However, isoflavone intake did not have a negative impact on women who were receiving tamoxifen or who had ER+/PR+ tumors.
- Of all ethnicities, Asian American women tended to have the highest isoflavone intakes at about 6 mg daily, but this amount was still much lower than women living in Asian countries who eat closer to 46 mg daily. The authors noted that American women appeared to benefit from eating smaller amounts of soy.
Another prospective study followed 1,954 American women who were breast cancer survivors for six years.  Key highlights of the study:
- Among postmenopausal women treated with tamoxifen, breast cancer recurrence was 60% lower when comparing the highest to the lowest daidzein (a specific type of soy isoflavone) No benefit was observed in women who had never used tamoxifen.
- Recurrence was lower with increasing isoflavone intake among women with tumors that were ER+/PR+ but not ER-/PR-.
- The most frequent sources of soy foods were not whole or minimally processed soy foods, but rather soy sauce, breakfast or diet drinks, tofu, diet bars, and soy protein isolate powder. The mean amount of isoflavones in the “high” category was about 19 mg daidzein and 27 mg genistein daily—a modest amount compared with Asian populations.
- The authors concluded that soy isoflavones eaten at levels comparable to those in Asian populations may reduce the risk of cancer recurrence in women receiving tamoxifen therapy and does not appear to interfere with tamoxifen efficacy. However, the findings need to be confirmed because they were mainly in subgroups and could be due to chance.
Prospective studies also find soy foods to be protective from breast cancer deaths:
- A cohort study of 1,460 Chinese women who were early-stage breast cancer survivors looked at dietary soy isoflavone intakes at baseline and after the breast cancer diagnosis, over a four-year period.  Higher soy intakes at baseline were associated with a 66% lower risk of deaths from any cause and a 64% lower risk of deaths from breast cancer. Higher soy intakes after diagnosis were associated with a 64% and 51% lower risk of deaths, from any cause and from breast cancer, respectively. The effects were greater in women who were premenopausal, had ER-/PR- tumors, and were taking tamoxifen.
- A meta-analysis of prospective cohort studies found a 12% reduction in breast cancer deaths with each 5 gram per day increase in soy protein intake. 
However, randomized controlled trials do not show an effect of soy foods on risk factors for breast cancer:
- A review of randomized controlled trials (RCTs) looked at isoflavone intakes ranging from 36-235 mg/day from food or supplements, taken from 1 month to 3 years, and breast cancer risk (as measured by breast density, changes in estrogen, and bloodwork) in healthy women.  The eighteen RCTs included both pre- and postmenopausal participants. No changes in breast cancer risk factors were found with isoflavone intakes. The authors noted limitations in their analysis in that there were wide variations in numbers of participants and the doses and duration of treatments, which made drawing firm conclusions difficult. Most importantly, these studies did not examine actual incidence of breast cancer.
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