The health topic most responsible for stimulating modern research investigation of soy foods, and the one that continues to dominate discussion today, is the relationship between soy and breast cancer, or more specifically, soybean isoflavones and breast cancer. New research makes a meaningful contribution in support of the hypothesis that soy consumption while young may reduce adult breast cancer risk, building on the evidence that has evolved over the past several decades. New research adds greatly to our understanding of this relationship [1].

In the early 1990s, the U.S. National Cancer Institute funded soy research largely based on the ability of soybean isoflavones to inhibit the development of mammary cancer in rats [2] and the historical low incidence rates of breast cancer in soy food- consuming countries, especially Japan [3]. However, in 1996, a pilot randomized controlled trial (RCT) failed to show that soy consumption favorably affects nipple aspirate section and raised concern about a possible stimulatory effect on breast tissue in premenopausal women [4]. Soon thereafter, research in mice showed that isoflavones stimulated the growth of existing estrogen-sensitive mammary tumors [5]. This finding is the genesis for the soy-breast cancer controversy.

However, over the subsequent years, observational studies that began to be published in 2009 [6] have shown that postdiagnosis soy intake is associated with reduced breast cancer recurrence and improved survival [7]. On this basis, both the American Cancer Society [8] and American Institute for Cancer Research [9], have concluded that soy foods may improve the prognosis of women living with breast cancer. Further, multiple RCTs show that neither soy nor isoflavone interventions affect markers of breast cancer risk including mammographic density and in vivo breast cell proliferation [7]. While these clinical results represent a strong argument for safety, they cast doubt upon the role of soy in reducing breast cancer, as was originally proposed. In contrast to the lack of effect of isoflavones, tamoxifen and aromatase inhibitors reduce mammographic density [10] and breast cell proliferation [11, 12].

Is there still a reasonable basis for speculating that soy isoflavone consumption reduces risk of developing breast cancer? There is, when one recalls the hypothesis proposed in 1995, based on studies in mice, that isoflavone intake, specifically when occurring early in life, is protective against breast cancer [13, 14]. This hypothesis, herein referred to as the early soy intake hypothesis (ESIH), is consistent with the school of thought as was highlighted by Colditz and Frazier [15] in that same year that early life events profoundly impact later risk of developing breast cancer.

The findings of all four relevant observational studies—two from China [16, 17] and two from the U.S. (involving women of Asian ethnicity) [18, 19]—are supportive of the ESIH. But importantly, the most recent of these was published a decade ago [17]. For that reason, and because clinical trials are lacking, the ESIH has remained an intriguing, but somewhat under the radar, hypothesis. However, newly published research supportive of the ESIH may help to change that. Ho and colleagues [1] from the Chinese University of Hong Kong, completed a study focused on the ESIH but instead of breast cancer risk, they examined mammographic density.

Breast tissue density, which can be non-invasively measured via mammography, is a well-recognized marker of breast cancer risk, as greater tissue density is associated with an increased breast cancer risk [20-22]. Ho et al. [1] measured the breast tissue density of 815 premenopausal women and assessed their intake of soy protein and isoflavones during four different periods of life: during the past 12 months (current), and during the time periods of 20–34, 13–18 and 6–12 years of age.

In brief, Ho et al. [1] found that when comparing high to low soy protein or isoflavone intake during those four periods, mammographic density was reduced in the younger age periods 6-12 and 13-18 years of age, but not in the older age periods of 20-34 years of age or current age. That is, consuming soy protein or soy isoflavones before adulthood was associated with lower mammographic density. Further, the difference in density was likely clinically relevant because its magnitude is similar to that associated with adolescent stature [23], the menopausal transition [24], conventional hormone therapy [25], and tamoxifen use [26]. An especially appealing aspect of the ESIH is that the proposed benefit—reduced breast cancer risk—is associated with the consumption of only one or perhaps at most two servings of soy foods daily.

At this point, it may be premature to recommend that young and adolescent girls consume soy foods specifically as a means of reducing breast cancer risk. More retrospective studies as well as intervention studies assessing gene expression and other relevant biomarkers in young and adolescent girls consuming soy are needed before a recommendation can be made. However, given the nutritional profile of soy foods, the ease with which they can be added to the diet, and the evidence that supports breast cancer protective effects, there are ample reasons for young females to consume soy foods.

This blog is supported by SNI Global and U.S. Soy.

References

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