Comment:

Summary:

Clinical Bottom Line

This meta-analysis concludes that higher consumption of soy isoflavones (defined as > 15 mg/day) is inversely correlated with the risk and occurrence of breast cancer in both pre-menopausal and post-menopausal women. The evidence, based on the statistical pooling of prospective studies, suggests a favorable outcome for women in the high-consumption group, with significantly fewer breast cancer cases compared to the low-consumption group (< 15 mg/day). Clinicians can interpret this as supporting the benefit of including soy and its isoflavones in a patient’s diet as a potential risk-reduction strategy.

Results

Summary of Results

The meta-analysis of prospective studies found a statistically significant inverse correlation between the amount of soy isoflavones consumed and breast cancer occurrence.

• Overall Breast Cancer Risk (All Study Populations): The statistical analysis across seven studies comparing the no-to-low consumption group (0-15 mg/day) to the high-consumption group (> 15 mg/day) showed a significant result (p < 0.000001) favoring the high-consumption group.
• Out of 9,699 breast cancer cases in these studies, 75% (7,271 patients) belonged to the low-consumption group.
• The pooled Odds Ratio (OR) was 7.01 (95% CI: 6.58-7.47), meaning the odds of a breast cancer diagnosis were approximately 7 times higher for the low-consumption group compared to the high-consumption group.
• Breast Cancer Risk by Menopausal Status: Separate analyses for pre- and post-menopausal women also showed a favorable and statistically significant result (p < 0.00001) for the high-consumption group.
  • Pre-menopausal Women: Out of 5,195 breast cancer cases, 77.3% (4,017 patients) were in the low-consumption group. The OR was 10.46 (95% CI: 9.56-11.44), reflecting a strong favorable association with higher consumption.
  • Post-menopausal Women: Out of 9,305 breast cancer cases, 77.5% (7,209 patients) were in the low-consumption group. The OR was 11.33 (95% CI: 10.58-12.13), also showing a similar, strong favorable association with high consumption.

Assertive Critical Appraisal

Certainty of Evidence (GRADE Framework)

The certainty of the evidence for the inverse correlation between high soy isoflavone consumption and breast cancer risk would likely be rated as Moderate.

The evidence is strong in terms of statistical significance (p < 0.00001), but the pooled results across all analyses show substantial heterogeneity (I² = 100% for the overall prevalence analysis, I² = 99% for others).

Heterogeneity

• The reported I² values are consistently high (98% to 100%) across the main analyses.
• The I² statistic represents the percentage of variation across studies that is due to real differences rather than just chance. An I² of 98% indicates substantial heterogeneity, suggesting that the included studies are showing widely different magnitudes of effect.
• The authors acknowledge this heterogeneity, attributing it to the different characteristics of the populations and the various methods used to categorize soy consumption across the primary studies. While the pooled ORs strongly favor high consumption, the substantial heterogeneity suggests that the true effect size may vary significantly depending on the specific population, region, or study design.

Publication Bias

The review’s authors do not explicitly state whether they assessed for publication bias (e.g., using a funnel plot or Egger’s test). This is a critical omission for a meta-analysis, as publication bias—the tendency for studies with significant or positive results to be published more readily—is a common threat that can lead to an overestimation of treatment effects.

Risk of Bias in Included Studies

The review included only prospective studies to address its question, which generally have a lower risk of recall and selection bias than retrospective designs. However, the primary data for isoflavone consumption was acquired via food frequency questionnaires, which are subject to measurement error and reporting bias. The review notes that included studies varied widely in their methodology, including the categorization of consumption groups (e.g., 0-15 mg/day vs. > 15 mg/day vs. other cut-offs).

Special Consideration for Pooled Results

It is important to note that the statistical power of a meta-analysis allows it to detect a trend that individual, smaller studies may fail to find. While the overall pooled result is highly statistically significant, this conclusion is derived from a collection of studies where results varied significantly (as indicated by the high heterogeneity). It is crucial to be mindful of this heterogeneity and the potential for publication bias when applying the strong pooled OR to clinical practice.

Reporting Quality Assessment (PRISMA)

The paper states that data gathering and search strategy followed PRISMA guidelines. A PRISMA flow diagram showing the study selection process (Figure 1) is included, which enhances the transparency and reproducibility of the review. The search query used for the four medical databases is also provided.

Applicability

The findings are highly applicable to general clinical practice, particularly in preventative health and dietary counseling. Soy isoflavones are readily available dietary components, and the study’s conclusion is relevant to the general female population (pre- and post-menopausal) regardless of ethnicity, as the included studies covered various populations including China, Japan, USA, Canada, and Australia.

Research Objective

The review’s question, framed using the PICO framework, is:

• P (Population): Pre-menopausal and post-menopausal women.
• I (Intervention/Exposure): High consumption of soy and isoflavones (defined in the analysis as > 15 mg/day).
• C (Comparator): Low or no consumption of soy and isoflavones (defined in the analysis as 0-15 mg/day).
• O (Outcome): Breast cancer risk and occurrence.

The primary objective was to determine whether the amount of soy and isoflavones consumed has a positive effect (reduced risk) in pre- and post-menopausal women.

Study Design

This document is a Systematic Review and Meta-analysis.

• Search Strategy: An extensive search of medical databases (PubMed, Medline, Google Scholar, and Embase) was performed for articles reporting an association between soy, isoflavones, and breast cancer. The search included articles up to April 2021.
• Study Selection Criteria: The analysis focused on prospective studies on human populations, written in English, with sufficient evidence on isoflavone consumption over an extended period and a comparison group with low/no consumption. Studies in other languages, cell-culture studies, animal studies, case series, and case reports were excluded.

Setting and Participants

• Total Studies Included: Eight prospective studies were ultimately included in the qualitative synthesis.
• Total Participants: The meta-analysis included data from patients around the world, with key studies from China, USA, Japan, Canada, and Australia. The number of participants in the studies that allowed for the overall analysis was 477,832.

Bibliographic Data

• Title: Soy Isoflavones and Breast Cancer Risk: A Meta-analysis
• Authors: IOANNIS BOUTAS, ADAMANTIA KONTOGEORGI, CONSTANTINE DIMITRAKAKIS, and SOPHIA N. KALANTARIDOU
• Journal: in vivo
• Year: 2022
• DOI: 10.21873/invivo.12737

Mandatory Disclaimer: This AI-generated analysis is for informational and research purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of a qualified health provider with any questions you may have regarding a medical condition.

Original Article:

Full text: here