Breast cancer is one of the most commonly diagnosed types of cancer at present, and it is the fifth leading cause of cancer-related deaths. A non-modifiable risk factor of breast cancer is the density of breast tissue. Breast density is categorized into several groups in clinical practice, including low-density, high-density, and fatty breasts. Higher breast tissue density is commonly observed in younger women, those with a lower body mass index (BMI), during pregnancy or breastfeeding periods, and in women undergoing hormonal replacement therapy. Higher breast density is associated with greater risks of breast cancer, a trend that is seen in both premenopausal and postmenopausal women.¹ Indeed, women with extremely dense breasts have an estimated 4 to 6 times higher risk of developing breast cancer compared to women with minimal breast density.²

Since mammographic density has been suggested to be an indicator of cell growth and division and is frequently used as a biological marker to indicate a person’s risk of developing breast cancer since the 1970s and a high level of mammographic density is associated with greater risk of breast cancer compared to low mammographic density, it is plausible that the effects of soy intake would be observable on mammograms.^3,4 Researchers have utilized both qualitative and quantitative measurements of breast density and quantitative assessments are a stronger detection choice. Most studies have defined breast density as the percentage of the breast occupied by dense tissue.⁵

Research on regions where breast cancer incidence is lower shows that dietary interventions, such as increased soy intake, may be an important strategy to reduce breast cancer risk. Asian populations, who traditionally consume soy-rich diets up to 10 times more than Caucasian women, have historically lower breast cancer rates.⁶ In Asian countries, where traditional soy-based foods like tofu and soy milk are commonly consumed, soy, soy-derived foods, and red clover are the richest dietary sources of isoflavones. Isoflavones include genistein, daidzein, and glycitein.⁷ Because of the structural similarity between plant-derived isoflavones and the human hormone 17β estradiol, it could have an effect on women’s health.^8,9 Indeed, isoflavones act as selective estrogen receptor modulators. It is suggested that isoflavones compete with the body’s own estrogen to bind to estrogen receptor sites. However, isoflavones have a weaker effect compared to the body’s natural estrogen, and therefore, they are believed to reduce overall estrogen exposure. Studies have demonstrated that soy isoflavones may be as effective as hormone replacement therapy in managing conditions associated with menopause, such as osteoporosis and menopausal symptoms.⁶

The present study aimed to synthesize the current evidence from the published literature by conducting a systematic review and meta-analysis. The objective was to outline the collective findings of studies that have examined the association between soy isoflavone intake and the mammographic density.

A comprehensive literature search was conducted across multiple databases to identify studies addressing the association between soy isoflavone intake and mammographic density. The search strategies were tailored to each database, and the total number of records retrieved is summarized in Table 1.

The methodological quality of the included studies was evaluated using the Newcastle-Ottawa Scale, which assesses 3 main domains—selection, comparability, and outcome/exposure assessment. Overall, most studies demonstrated moderate to high quality, particularly in the selection domain, where sample recruitment and data sources were adequately described. However, in several studies, details regarding the method used to measure mammographic density lacked clarity, potentially introducing measurement bias. Despite these limitations, the Newcastle-Ottawa Scale results suggest that the majority of the included studies provide reliable data and contribute substantially to the overall evidence base of this review.

The results of our analyses revealed that the soy-receiving groups had 8% lower mammographic densities compared to the placebo-receiving group, which was statistically significant (Figure 2).

In this study, BMI was analyzed as a secondary outcome to explore its association with the primary outcome (mammographic density). While the primary focus was on the intervention’s effect on mammographic density, BMI was included to understand its role as a potential modifier or confounder. The 2 groups had statistically different BMI values as the soy receiving group had 19% higher BMI values than the control group (Figure 3).

The correlation between soy consumption and the risk of developing breast cancer has shown varying results in observational epidemiological studies. Following the initial findings by Lee et al. in a case-control study conducted in Singapore, which demonstrated a significant protective effect in premenopausal women¹⁶, similar strong effects were observed in subsequent case-control studies among premenopausal women in Japan¹⁷ and in Asian-born women residing in the United States. A recent cohort study conducted in Japan similarly demonstrated a decreased risk of breast cancer when individuals consumed high levels of isoflavones.¹⁸ A study conducted in China¹⁹ and among Asian-Americans in Los Angeles County²⁰ indicated that consuming a large amount of food during adolescence has a protective effect. Nevertheless, additional Chinese studies and a prospective study investigating the impact of consuming tofu and miso soup in Asian women did not yield statistically significant results. In addition, several studies conducted on non-Asian women, who consumed significantly lower amounts of soy, had mostly yielded unclear results. A recent analysis²¹ concluded that the overall data showed no negative relationship between soy consumption and the incidence of breast cancer, except for a potential impact of consuming soy at a young age and consuming high amounts in specific Asian groups.²² The findings align with the conclusions of the recent analysis, suggesting that consuming high amounts of soy may have a preventive impact against breast cancer. This effect may be due to the effect of soy intake on mammographic density.

This study examined the relationship between self-reported soy food intake and breast size in healthy pre- and postmenopausal women who had mammography screening. The results showed that there was a negative correlation between soy food intake and breast size, namely in the non-dense area, as evaluated in mammographic pictures. In contrast to our initial hypothesis, they observed a positive correlation between the consumption of soy and the proportion of breast tissue, as well as higher levels of breast tissue proportion among Chinese and Japanese women who had a lower likelihood of developing breast cancer. These findings suggest that soy may contribute to an increased risk of breast cancer due to its estrogenic properties. An alternative argument, however, may be that the size of the non-dense patches, which is inversely related to soy, is significant in determining breast cancer risk. The presence of a tumor in the mammary gland has been suggested as a potential risk factor for breast cancer. This is due to the increased development of ductal stem cells, which is influenced by factors during pregnancy and high energy consumption in early life. While these researchers did not gather data on soy consumption during childhood, they suggested that soy foods, whether consumed alone or as part of an Asian diet that is low in fat, high in cereal, and low in dairy and red meat, may play a role in the variations in mammographic characteristics among different ethnic groups. Dietary patterns can be determined from nutritional data using factor analysis, as demonstrated in various papers.²⁵

Our hypothesis suggests that soy consumption throughout the developing years may influence mammographic characteristics by reducing the fat component of the breast. This effect is believed to be due to soy’s impact on the growth of the female breast during that specific period. Comparative growth studies²⁶ provide evidence for the significance of childhood nutrition in determining adult anthropometric parameters. A dietary effect on breast development before puberty accords with the results from migrant studies revealing that it takes two or more generations to raise breast cancer risk.¹⁸ The temporal lag suggests that only the offspring of migrants who were born and raised in the host nation will have a similar risk as the local population. This shows that potential environmental and behavioral factors have an impact early in life or during pregnancy.²⁷ Furthermore, there is data indicating that exposures during the neonatal period and adolescence play a significant role in determining the risk of developing breast cancer later in life, in addition to the indications provided by migration studies. The incidence of high-risk mammographic patterns, for example, was related to the weight of the placenta, the primary estrogen-producing organ during pregnancy.²⁸

A Western diet, as opposed to an Asian one, may lead to increased body fat mass¹⁸ during preadolescence, mediated through more accessible sex steroids. The high soy component of Asian diets may possibly limit the release of sex hormones and their effects on body fat through the antiestrogenic actions of isoflavones.²⁹

The greater percentages of mammographic density seen among Asian women do not necessarily contradict the hypothesis of mammographic density. It appears from a recent case–control study that the connection between percentages of densities and breast cancer is of equal strength in women of different ethnicities despite the fact that density levels vary by ethnicity. While the connection between soy consumption and mammographic densities has not been explored before, earlier dietary research³⁰ has indicated limited correlations between micro- and macronutrients and mammographic densities. In a case-control study, there was a positive correlation between energy-adjusted saturated fat intake and mammographic densities, while fiber and carotenoids showed an inverse correlation.

The intervention group experienced a 6.1% decrease in areas of density, while the control group only had a 2.1% decrease, during a reduced fat intervention.³¹ A reduction in cholesterol and saturated fat consumption, specifically, was found to be associated with a decrease in mammographic density. Increased consumption of fats and elevated levels of high-density lipoprotein cholesterol^23,33,34 were shown to be associated with denser mammographic patterns, indicating a potential link between blood lipid levels and the risk of breast cancer. A recent study³² on a large group of Caucasian women found that there were slight variations in mammographic densities based on levels of vitamins B12, C, and E, as well as polyunsaturated fat intake.

Possible disparities in video quality between clinics and subjects could have resulted in measurement inaccuracies. In order to reduce the subjective element of the assessment process, they dedicated significant efforts to educating the readers and regularly compared the findings among them. The strong correlation coefficient suggests a significant degree of standardization in mammographic evaluation. Due to the inaccuracies in measuring dietary and mammographic density, the complex nature of determining mammographic densities, and the inherent bias in recalling dietary information, it is challenging to detect a minor impact. Given that the main objective of this study was to investigate the relationship between soy food consumption, we did not explore beneficial outcomes across various food items.

The absence of a comprehensive record of soy consumption throughout one’s life and the use of a cross-sectional research methodology restrict the capacity of our investigation to demonstrate causal relationships. The dietary assessment inquired solely about consumption over the previous year. Consequently, it is unclear if the consumption of soy at the period when breast development took place was comparable to the current level of intake. It is possible that the influence of soy on the appearance of mammography in Caucasian women was not observed because those who reported soy intake likely began consuming these foods later in life, rather than during childhood. However, the consumption of soy may serve as an indication of Chinese and Japanese ethnicity, as well as a sign of childhood dietary habits that encompass various nutritional factors, including but not limited to soy-based foods. These eating habits may account for some physical measurements observed in adult women.

To conclude, this meta-analysis revealed that the Soy receiving group had 80% lower mammographic densities compared to the placebo-receiving group which was statistically significant. Therefore, soy could be considered as an effective supplementary therapy. However further large scaled observational studies are still required to support these findings.

As this study is a review of published literature, no ethical approval or consent was required.

The data are not public but are available upon request from the corresponding author.