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Secondary article_Closeup-Of-A-Muslim-Woman-In-H_RESIZED (1)

DOES POSTDIAGNOSIS SOY INTAKE IMPACT BREAST CANCER OUTCOMES?

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Despite 30 years’ worth of research, the question of whether postdiagnosis soy intake impacts breast cancer outcomes cannot be definitively answered because the necessary clinical data to do so are not available. However, dietary advice based on imperfect data is routinely issued. In fact, most of the understanding about diet/health relationships, especially as related to chronic disease risk, is based on the results of observational studies (which do not allow cause and effect relationships to be established).

As highlighted below, in the case of soy and women with breast cancer, there is an impressive body of evidence upon which intake recommendations can be based.

Origins of the Controversy

The classification of soybean isoflavones as phytoestrogens, despite being much different than the hormone estrogen;1 and the lack of evidence that estrogen therapy worsens the prognosis of women with breast cancer2,3 provided a conceptual basis for concern.

The stimulatory effect of isoflavones on the growth of existing estrogen-sensitive mammary tumors in athymic ovariectomized mice, first reported in the late 1990s, is generally seen as the genesis of the soy and breast cancer controversy.4,5

Clinical Studies

In healthy women, at-risk women, and women with breast cancer, isoflavones delivered in the form of supplements or soy protein -- even in amounts greatly exceeding typical Asian intake -- have no effects on markers of breast cancer risk including mammographic density6-19 and breast cell proliferation.20-25

In contrast to isoflavones, combined hormone therapy (estrogen plus progestin) adversely impacts breast cancer risk markers26,27 and increases breast cancer risk,2 whereas drugs used to treat breast cancer favorably impact these markers and disease outcomes.28-30

Prospective Studies

Seven prospective observational studies have examined the impact of postdiagnosis soy intake on breast cancer recurrence and/or survival. One study was conducted in Hong Kong,31 and two each in China,32,33 the U.S.,34,35 and Korea.36,37 (Note: only studies involving sufficient isoflavone intake are being considered for reasons discussed in the reference.38) Postdiagnosis soy intake is associated with reduced recurrence and there is suggestive evidence that breast cancer-specific mortality is also reduced.39-41

Results According to Breast Cancer Type

In a combined analysis of the largest Chinese study32 and the two U.S. studies,34,35 soy intake was protective against both estrogen receptor-positive (ER+) and estrogen receptor-negative breast cancer but more so against the latter. However, in this same analysis, soy was more protective for women on tamoxifen who undoubtedly had ER+ breast cancer.39

The Following are Scientifically Supported Responses to Frequently Asked Questions Regarding Postdiagnosis Soy Intake and Breast Cancer.

Q: Do results differ according to the type of soy consumed?

A: Clinical trials have intervened with either isoflavone supplements or isoflavone-rich soy protein. Observational studies have involved free-living populations, specifically from soy food-consuming countries or individuals of Asian ethnicity, so consumption came in the form of traditional Asian soy foods like tofu, edamame, and tempeh.

Q: Does soy impact the efficacy of endocrine therapy?

A: Very limited clinical data suggest isoflavones do not interfere with tamoxifen treatment.39 Similarly, limited observational data indicate soy does not impact the efficacy of endocrine therapy for breast cancer, including both tamoxifen and aromatase inhibitors.39,42

Q: How much soy or isoflavones were consumed in the relevant clinical and epidemiologic studies?

A: In the clinical studies, isoflavone intake was typically 40-100mg/d, the equivalent of about 2-4 servings of traditional Asian soy foods like tofu, edamame, and tempeh, but in a few cases, intake greatly exceed 100mg/d. In the observational studies, intake in the highest intake category ranged from about 25mg/d-100mg/d.

Conclusions

If human research alone was considered, recommendations would likely be for women with breast cancer to consume soy foods because the clinical data are supportive of safety and the observational data suggestive of benefit. As it stands, health and cancer organizations consistently conclude that women with breast cancer can safely consume soy foods and note the possibility that doing so may improve cancer outcomes. However, it is important to consider the limitations of the data, and a cautious interpretation of the literature is warranted.

Plant-based diets are recommended for women with breast cancer, specifically to improve outcomes as well as for overall health. Given that soy foods undoubtedly make adhering to such diets easier, there is ample reason for women with breast cancer to consider including soy foods in their diet.

REFERENCES

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  2. Chlebowski RT, Anderson GL, Aragaki AK, et al. Association of menopausal hormone therapy with breast cancer incidence and mortality during long-term follow-up of the Women's Health Initiative randomized clinical trials. JAMA. 2020;324(4):369-80. https://10.1001/jama.2020.9482
  3. Fahlen M, Fornander T, Johansson H, et al. Hormone replacement therapy after breast cancer: 10 year follow up of the Stockholm randomised trial. Eur J Cancer. 2013;49(1):52-9. https://10.1016/j.ejca.2012.07.003
  4. Hsieh CY, Santell RC, Haslam SZ, Helferich WG. Estrogenic effects of genistein on the growth of estrogen receptor- positive human breast cancer (MCF-7) cells in vitro and in vivo. Cancer Res. 1998;58(17):3833-8.
  5. Helferich WG, Andrade JE, Hoagland MS. Phytoestrogens and breast cancer: a complex story. Inflammopharmacology. 2008;16(5):219-26. https://10.1007/s10787-008-8020-0
  6. Maskarinec G, Williams AE, Carlin L. Mammographic densities in a one-year isoflavone intervention. Eur J Cancer Prev. 2003;12(2):165-9.
  7. Maskarinec G, Takata Y, Franke AA, Williams AE, Murphy SP. A 2-year soy intervention in premenopausal women does not change mammographic densities. J Nutr. 2004;134(11):3089-94.
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About The Author:

Mark Messina, PhD, MS, is chairperson of the Soy Connection editorial board and director of nutrition science and research for Soy Nutrition Institute (SNI) Global. He is also the co-owner of Nutrition Matters, Inc., a nutrition consulting company, and is an adjunct professor at Loma Linda University. His research focuses on the health effects of soy foods and soybean components.

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