Soy compounds known as isoflavones are among a few plant-derived compounds that may significantly reduce the risk of breast cancer recurrence or death.  This is the conclusion based on a new meta-analysis co-directed by investigators from the Johns Hopkins Kimmel Cancer Center.

The outcomes of the study were published on January 10, 2024 in the journal JNCI Cancer Spectrum. [1]

Investigators in Australia, Denmark, England, Norway and the United States reviewed 22 published observational studies that examined the impact of dietary intake of soybeans, lignans (compounds found in a variety of plants including seeds and nuts), cruciferous/cabbage-family vegetables, and green tea — and these substances’ phytonutrients (natural compounds derived from plants) — on breast cancer recurrence and mortality, as well as on mortality from all causes.

This meta-analyses also included 11 studies of soy isoflavones, three of cruciferous vegetables, two of green tea, three of lignans, and three of enterolactone, which is formed in the gut when lignans are digested.

Reduced risk
Soy isoflavones were associated with a 26% reduced risk of breast cancer recurrence (HR = 0.74, 95% CI = 0.60 to 0.92), according to a meta-analysis that included six of the studies (of 11,837 women)  reviewed by investigators. These results were most notable among post-menopausal survivors (HR = 0.72, 95% CI = 0.55 to 0.94) and estrogen receptor-positive survivors (HR = 0.82, 95% CI = 0.70 to 0.97). The greatest risk reduction was seen at 60 milligrams per day.

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This is equivalent to two to three servings per day, where one serving equates to a cup of soy milk, three ounces of tofu or a half-cup of cooked soybeans. However, the effect of soy consumption on risk of mortality was smaller (12%) and not statistically significant, and was seen mostly at 20-40 mg per day, or one to two servings.  Overall, a diet of soy protein and products were inversely associated with cancer-specific mortality for estrogen receptor-positive disease (HR = 0.75, 95% CI = 0.60 to 0.92).

Another finding, reported for the first time in a meta-analysis, relates to enterolactone, a compound metabolized from lignans. Lignans are found in a wide variety of plants, such as seeds, nuts, legumes, whole grains, fruit and vegetables. High levels are found in flaxseeds, cashew nuts, broccoli and brussels sprouts, among other sources.

Enterolactone was found to reduce the risk of breast cancer-specific mortality by 28% (HR = 0.72, 95% CI = 0.58 to 0.90) and death from any cause by 31% (HR = 0.69, 95% CI = 0.57 to 0.83) particularly in post-menopausal women (35% reduction in death from any cause).

It is not possible to calculate the effective dose of lignans in the diet from these enterolactone findings, because the gut microbiome that plays a role in metabolism of lignans varies among individuals.

“These findings were graded probable, which means there is strong research showing that they contributed to the results we are seeing,” explained lead study author Diana van Die, Ph.D., of NICM Health Research Institute at Western Sydney University, Australia.

The review also found some suggestive results, which means the results are generally consistent but rarely strong enough to justify recommendations:

  • Pre-diagnostic consumption of green tea suggests an effect of reducing the risk of breast cancer recurrence by 44% in women with stage I or II breast cancer (HR = 0.56, 95% CI = 0.38 to 0.83). The greatest effect was seen from consuming three to five cups per day and from five or more cups per day, as documented in two Japanese studies.
  • Among those who consumed lignans prior to breast cancer diagnosis, there was a non-significant 34% risk reduction in cancer-specific mortality and 19% reduction in all causes of death in post-menopausal women. However, consumption of lignans by pre-menopausal women suggests an increased risk of mortality. This result indicates that the effects of lignans are dependent on the hormonal environment, although it was likely driven by one large study and needs further investigation. The highest intake was nine or more servings per day in the studies reviewed.
  • The impact of cruciferous vegetables was inconclusive, possibly influenced by the average intake being quite low (less than a half-cup per day) in the studies reviewed.
Channing Judith Paller, M.D. is Director, Prostate Cancer Clinical Research, Associate Professor of Oncology. Paller is a medical oncologist at Sibley Memorial Hospital and an associate professor of oncology at the Johns Hopkins University School of Medicine. She practices out of the Prostate Cancer Multidisciplinary Clinic at Sibley Memorial Hospital in Washington, D.C., and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, MD. Photo courtesy: © 2020 – 2024 Johns Hopkins University School of Medicine. Used with permission.

Not an alternative treatment
Investigators also looked into whether consuming soy, lignans, cruciferous vegetables and green tea, or their phytonutrients in the diet before or after breast cancer diagnosis made a difference. However, the data did not provide a concrete answer. All studies on green tea and lignans measured pre-diagnosis intake, while soy results came from studies that measured intake before and after diagnosis.

“It is critically important to stress that these studies were conducted on women who received medical and/or surgical treatment for breast cancer, and that these foods and phytonutrients should not be considered as alternatives to treatment,” says senior study author Channing Judith Paller, M.D., director of prostate cancer clinical research and an associate professor of oncology at Johns Hopkins.

“This research highlights the need for more robust studies in this area looking at the most effective dosages of these compounds, and whether starting to consume them after diagnosis has the same effect as a lifelong dietary habit before diagnosis. This is what patients are looking for,” Paller added.

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Note: Kala Visvanathan, M.D., M.H.S., director of the Clinical Cancer Genetics and Prevention Service at the Kimmel Cancer Center, was a co-author of the review. Additional co-authors were from Integria (MediHerb) in Australia, the Danish Cancer Institute, Imperial College London, Oslo New University College and The Cancer Registry of Norway.

Reference
[1] van Die MD, Bone KM, Visvanathan K, Kyrø C, Aune D, Ee C, Paller CJ. Phytonutrients and outcomes following breast cancer: a systematic review and meta-analysis of observational studies. JNCI Cancer Spectr. 2024 Jan 4;8(1):pkad104. doi: 10.1093/jncics/pkad104. PMID: 38070485.

Photo courtesy Fernando Andrade on Unsplash. Used with permission.

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