Human studies indicate that the intake of soy reduces the risk of breast cancers, but are isoflavones healthy or risky for breast cancer patients and survivors? Many studies have demonstrated the anticancer properties of soy isoflavones, but its estrogen-like effect and conflicting data from in-vivo and in-vitro studies have raised concern about isoflavones intake and the promotion or propagation of estrogen-sensitive cancers. Some health professionals still remain confused and even recommend that breast cancer survivors should not consume soy or isoflavones supplements.
In-vitro and animal studies
A review of in vitro studies found that low levels of isoflavones promote the growth of estrogen-sensitive breast cancer cells, but inhibit cell growth at higher levels [1].
Many in vitro studies that showed genotoxic effects of genistein have used genistein in high doses that cannot be obtained in humans by intake of natural dietary products. However, Imhof found that low levels of isoflavones inhibited the growth of breast cancer cells when they were co-incubated with low levels of estradiol, which are even present in postmenopausal women [2]. Imhof concluded that his findings emphasized the reported advantageous properties of isoflavones for postmenopausal women.
A recent study by Liu and co-workers at the State University of New York concluded that daidzein and its metabolite equol inhibited the growth of mammary tumors in rodents. The scientists were optimistic that daidzein or equol could be used in new drugs for treating breast cancer. They also suggested that the consumption of daidzein may protect against breast cancer [7].
Human studies
According to a review by Taylor et al, Asian epidemiological studies attribute reduced incidence of breast and prostate cancers to soy food and isoflavones consumption [3]. Concerns are mainly based on in vitro and animal studies which suggest that genistein can stimulate tumor cell proliferation and growth in mice having deficient immune systems. But recent case-control study and epidemiological studies show an inverse correlation between genistein intake and breast cancer risk. Clinical studies on postmenopausal women confirm the breast and uterine safety of pure genistein administered for up to 3 years. A recent population-based cohort study that attracted worldwide attention concluded “that among women with breast cancer, soy food consumption was significantly associated with decreased risk of death and recurrence” [4]. Shu and co-workers found that women with the highest intake of soy protein (>15 g soy protein per day) had a 29 percent lower risk of death and 32 per cent lower risk of breast cancer recurrence compared to patients with the lowest intake (<5.3 g soy protein per day). This inverse relationship was evident among women with both estrogen receptor positive and estrogen receptor negative breast cancer. The association of soy isoflavones with mortality and breast cancer recurrence followed a dose-dependent pattern until soy isoflavones intake reached 40 mg per day, after which the association appears to level or even rebound. They suggest that soy isoflavones protects against breast cancer by competing with estrogens in the binding of estrogen receptor. A recent study found that intake of isoflavones was associated with lower risk of recurrence among postmenopausal patients with breast cancer, positive for estrogen and progesterone receptor, and those patients who received anastrozole as endocrine therapy [5].
An article published in Cancer recommends that women should consume soy foods because of its health benefits [8]. Soy foods not only prevent breast cancer but also benefit women who have already have breast cancer.
Effect of isoflavones on tamoxifen
In some experimental studies the inhibitory effect of tamoxifen drug that is commonly used to prevent recurrence and prolonging survival on the growth of implanted mammary tumors were negated by the administration of isoflavones, but other studies showed that isoflavones caused a synergistic effect on the growth inhibition by tamoxifen. One study that raised concern about the safety of genistein was an experiment with rodents carried about by Helferich and co-workers [6]. They implanted estrogen-dependent tumours into ovariectomized mice and found that dietary genistein was able to negate the inhibitory effect of tamoxifen on tumour growth. Most importantly epidemiological data showed that soyfood intake by breast cancer patients was associated with improved survival, also for women who took the anti-cancer drug tamoxifen [4]. These results indicate that isoflavones do not reduce the efficacy of tamoxifen.
Isoflavones supplements and breast cancer risk
Most human studies that demonstrated the protective effect of isoflavones looked at the intake of soy foods and not isoflavones supplements. Not enough studies have been done to determine whether or not high concentrations of isoflavones may encourage the growth of breast cancer. If you’re taking soy supplements to treat menopausal symptoms, speak with your health professional about quantity of isoflavones that may be safe for you.
Conclusion
Epidemiological studies suggest that soyfood and isoflavones may reduce breast cancer risk and may have beneficial effect on breast cancer survivors. However, it cannot be ruled out that isoflavones could promote breast cancer in postmenopausal women. Intake of high levels of purified isoflavones by these women is not without risk.
References
[1] Klein et al. Genistein genotoxicity: critical considerations of in vitro exposure dose. Toxicol Appl Pharmacol. 2007 Oct 1;224(1):1-11.
[2] Imhof et al. Effects of soy isoflavones on 17beta-estradiol-induced proliferation of MCF-7 breast cancer cells.
[3] Taylor et al. The effect of genistein aglycone on cancer and cancer risk: a review of in vitro, preclinical, and clinical studies. Nutr Rev. 2009 Jul;67(7):398-415.
[4] Shu et al. Soy food intake and breast cancer survival. JAMA. 2009 Dec 9;302(22):2437-43.
[5]Kang et al. Effect of soy isoflavones on breast cancer recurrence and death for patients receiving adjuvant endocrine therapy. CMAJ. 2010 Oct 18.
[6] Helferich et al. Phytoestrogens and breast cancer: a complex story. Inflammopharmacology. 2008 Oct;16(5):219-26.
[7] Liu X et al. Anti-breast cancer potential of daidzein in rodents. Life Science. 2012 Oct 5;91(11-12):415-9.
[8] O Kucuk. Soy foods, isoflavones, and breast cancer. Cancer. 06 March 2017.