Can Soy, Lignans, and EGCG Help Breast Cancer Survivors? What a New Systematic Review Says

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A new systematic review and meta-analysis found that specific doses of soy isoflavones, flaxseed lignans, and green tea EGCG were associated with significantly reduced risk of breast cancer recurrence and mortality. The study provides guidance on the most effective dosages of these natural compounds for supporting breast cancer survival.

For breast cancer survivors, the fear of recurrence is never far from mind. But what if compounds from plants like soy, flaxseed, and green tea could help reduce that risk and improve long-term outcomes? A groundbreaking new study sheds light on the potential of these phytonutrients - and the specific doses that may make the most impact.

Breast cancer is the most common cancer in women worldwide, with over 2 million new cases diagnosed each year.1 While advancements in detection and treatment have improved survival rates, recurrence remains a pressing concern for the millions of breast cancer survivors.2 However, a new systematic review and meta-analysis published in JNCI Cancer Spectrum suggests that certain plant-based compounds, or phytonutrients, may help reduce the risk of recurrence and improve long-term outcomes.3

The study, conducted by researchers from institutions in Australia, the United States, Denmark, the United Kingdom, and Norway, analyzed data from 32 observational studies involving over 63,000 breast cancer survivors.3 It looked at the impact of soy isoflavones, flaxseed lignans, green tea epigallocatechin-3-gallate (EGCG), and cruciferous vegetables on breast cancer recurrence, breast cancer-specific mortality, and all-cause mortality.3

Soy isoflavones, at a dose of 60 mg per day, were associated with a significant 26% reduction in the risk of breast cancer recurrence, particularly among postmenopausal women and those with estrogen receptor-positive tumors.3 For mortality outcomes, the greatest risk reductions were seen at 20-40 mg of isoflavones per day.3 Soy protein and soy products were also linked to a 25% lower risk of breast cancer-specific mortality for estrogen receptor-positive disease.3

The mammalian lignans enterolactone and enterodiol, formed by the gut microbiota from plant lignans like those in flaxseed, demonstrated a 28% decreased risk of breast cancer-specific mortality and 31% lower all-cause mortality risk when measured either before diagnosis or in the early period after diagnosis.3 These associations were strongest for postmenopausal women and those with node-negative disease.3 Dietary lignan intake alone did not show a significant association with mortality outcomes.3

For green tea, prediagnostic intake was linked to a notable 44% reduction in recurrence risk for stage I and II breast cancer.3 The two studies examining green tea observed the greatest effects at 3-5 cups per day and 5 or more cups per day.3 The key active component EGCG is thought to be responsible for green tea's anticancer properties.

In contrast, no significant associations were seen for cruciferous vegetable intake and breast cancer outcomes in this analysis.3 However, the highest intakes in the included studies were less than one 78g serving per day on average, far lower than the therapeutic doses used in research on isolated cruciferous-derived compounds.3

The researchers used the WCRF/AICR Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria for breast cancer survivors to assess the strength of the evidence.4 Soy isoflavones and enterolactone were rated as having "probable" evidence for recurrence and mortality risk reduction, respectively, while the evidence for green tea and recurrence was deemed "limited suggestive."3

Several biological mechanisms may explain the beneficial effects of these phytonutrients. Soy isoflavones and mammalian lignans act as selective estrogen receptor modulators (SERMs), exhibiting tissue-specific estrogen agonist or antagonist activity.5 They preferentially bind to estrogen receptor beta, which is thought to counteract the proliferative effects of estrogen receptor alpha activation in breast tissue.5 Green tea EGCG has demonstrated antiproliferative effects, aromatase inhibition, and synergistic activity with conventional cancer therapies in human studies.6

The safety of soy for breast cancer patients has been a topic of debate due to concerns that its weak estrogenic activity could stimulate tumor growth. However, this meta-analysis found no evidence that soy interferes with the efficacy of tamoxifen treatment, with similar risk reductions seen in tamoxifen users and non-users.3 The doses of soy isoflavones associated with benefit in this study are consistent with current recommendations from major cancer organizations.7

While this systematic review sheds new light on the role of phytonutrients in breast cancer survivorship, it also highlights the need for more research. Few of the included studies measured postdiagnostic changes in intake of these compounds, so the impact of adding them to the diet after diagnosis remains unclear.3 Future studies should use consistent definitions of outcomes, stratify results by menopausal status and tumor hormone receptor expression, and assess intake at multiple timepoints after diagnosis.3

For breast cancer survivors and their healthcare providers, this study offers valuable insights into the potential of plant-based compounds to improve prognosis. While not a substitute for conventional treatment, soy, flaxseed, and green tea may be beneficial adjuncts to a healthy lifestyle after a breast cancer diagnosis. As always, patients should consult with their oncology team before adding any new supplements to their regimen. With further research, we may unlock more of nature's potential for supporting survivors on their journey beyond breast cancer.

For more information on the potential health benefits of soy products visit our database on the subject here.

For research on natural approaches to breast cancer, visit our database on the subject here.


References

1. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians. 2021;71(3):209-249. doi:10.3322/caac.21660

2. Bergin ART, Loi S. Triple-negative breast cancer: recent treatment advances. F1000Res. 2019;8:F1000 Faculty Rev-1342. Published 2019 Aug 2. doi:10.12688/f1000research.18888.1

3. van Die MD, Bone K, Visvanathan K, et al. Phytonutrients and Outcomes Following Breast Cancer: A Systematic Review and Meta-Analysis of Observational Studies. JNCI Cancer Spectrum. 2023;8(1):pkad104. doi:10.1093/jncics/pkad104

4. World Cancer Research Fund/American Institute for Cancer Research. Continuous Update Project Expert Report 2018. Diet, nutrition, physical activity and breast cancer survivors. Available at dietandcancerreport.orghttps://www.wcrf.org/diet-activity-and-cancer/breast-cancer-survivors/

5. Bhattacharya T, Dutta S, Akter R, et al. Role of Phytonutrients in Nutrigenetics and Nutrigenomics Perspective in Curing Breast Cancer. Biomolecules. 2021;11(8):1176. Published 2021 Aug 6. doi:10.3390/biom11081176

6. Yiannakopoulou EC. Interaction of Green Tea Catechins with Breast Cancer Endocrine Treatment: A Systematic Review. Pharmacology. 2014;94(5-6):245-248. doi:10.1159/000369170

7. American Institute for Cancer Research. Soy: Intake Does Not Increase Risk for Breast Cancer Survivors. https://www.aicr.org/cancer-survival/healthy-or-harmful/soy/

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