Soy Phytoestrogens and Breast Cancer: An Enduring Dilemma
The impact of soy consumption on breast cancer diagnosis and outcome has remained of concern to clinicians and researchers for the past 20 years. Although studied extensively in epidemiologic studies as well as lab and animal research, no medical consensus on soy’s effects has emerged. Many studies show that soy intake is associated with reduced incidence of breast cancer risk,1-3 but soy’s phytoestrogen content continues to fuel concern that it may promote tumor growth, especially in estrogen-sensitive breast cancer.
This is a major issue of confusion for patients, who are exposed to conflicting media reports and marketed soy products with poorly supported health claims. Inconsistency in research findings, noncomparable study designs, and a dearth of clinical trials that assess the effect of soy on breast cancer outcome in humans have precluded the development of rigorous evidence-based guidelines to date. In this overview, we aim to summarize relevant findings and existing recommendations that may be useful to clinicians.
Estrogenic Activity of Soy Isoflavones
Soy (Glycine max) is a major source of isoflavones, particularly genistein and daidzein. These compounds are structurally similar to endogenous estrogen, and may act as selective estrogen receptor modulators with the ability to stimulate or inhibit depending on factors such as isoflavone concentration and the distribution of estrogen receptor types. Isoflavones also may modulate breast carcinogenesis via nonhormonal pathways.4
Although many in vitro and preclinical results suggest that soy isoflavones have antiproliferative effects,5 other studies suggest that they can promote the growth of breast cancer cells. Much of this research used isolated genistein. However, data from at least one animal study in which soy isoflavones promoted tumor growth suggests that this effect is not seen when whole soy is consumed instead of isoflavones alone.6
The effects of soy isoflavones in patients on tamoxifen therapy are similarly unclear; both synergistic and antagonistic interactions are reported.7 The exact nature and clinical implications of the estrogenic and antiestrogenic properties of isoflavones are not well understood.
To reduce the risk of breast cancer, epidemiologic evidence generally describes an inverse relationship between soy consumption and breast cancer diagnoses, although the observed degree of protective benefit varies depending on the patients studied. While some reviews and meta-analyses suggest that soy intake reduces breast cancer risk only modestly if at all,1,8 other studies have found that consumption at higher levels, such as in Asian diets, may have a more distinct protective effect.3 Asians traditionally consume a much higher concentration of isoflavones than their Western counterparts—daily consumption in Japan ranges from 26 to 54 mg, compared to 0.5 to 3 mg in the United States.9
Both dosage and timing of exposure to soy isoflavones appear relevant to their potential chemopreventive effect. Two recent meta-analyses2,3 found soy intake to be significantly associated with reduced risk of breast cancer in Asian but not Western populations, which may be explained by both higher soy intake among Asians and their tendency to consume soy from an early age.
Several epidemiologic studies in fact suggest that diets rich in soy early in life and through puberty are associated with a decreased risk of breast cancer—and that introducing isoflavones into the diets of adult women may not have much impact on their cancer risk.10 This is generally consistent with animal studies, which suggest that soy intake is protective at specific stages of development but not at other points.11
Despite the inconsistent results of lab and animal studies and resulting concerns about whether soy might adversely affect breast cancer prognosis, there is a growing body of research in humans that supports soy consumption as safe. Three large epidemiologic studies published over the past few years, two in U.S. breast cancer survivors12,13 and one in Chinese survivors,14 found no adverse affects of soy consumption on outcome. Furthermore, they suggest that soy consumption at levels comparable to those among Asian populations does not detract from the benefits of tamoxifen therapy, and may even offer some protection against recurrence and cancer-related death. The largest of these studies, published in the Journal of the American Medical Association in 2009, followed 5,033 breast cancer survivors for a median of 4 years.14
Based on these studies, the most recent guidelines from the American Cancer Society (ACS), released in April 2012, conclude that for breast cancer survivors, “current evidence does not suggest that consuming soy foods is likely to have adverse effects on risk of recurrence or survival.”15 It warns, however, that evidence “is more limited” with regard to isoflavone supplements.
The ACS position gained further support just 1 month after its release from an even larger study of 9,514 U.S. and Chinese breast cancer survivors, which found a significantly reduced risk of cancer recurrence in patients who consumed at least 10 mg of isoflavones (~3 g of soy protein) per day.16 The guideline does not mention a specific amount of soy that should be considered safe, unlike the previous ACS report on this topic in 2006, which specified a maximum of “three servings per day of soy foods.”17
Despite some contradictory evidence in lab studies and animal models, a growing body of epidemiologic evidence suggests that soy food is safe to consume at moderate levels, and that clinicians need not advise against soy foods for breast cancer patients or survivors. Patients should avoid soy supplements, however, as these often provide very high doses of isoflavones and have not been well studied. More research and, ideally, human clinical trials, are needed to elucidate the optimal dosage and timing of exposure for maximizing the anticancer effects of soy while minimizing the risk of harm. ■
Disclosure: Dr. Cassileth and Mr. Yarett reported no potential conflicts of interest.
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