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Circulating inflammatory biomarkers, adipokines and breast cancer risk-a case-control study nested within the EPIC cohort.

Cairat et al,

2022

BMC Med

A large European study measuring inflammatory markers in the blood of over 3,000 women found that inflammation’s relationship with breast cancer risk differs dramatically by menopausal status, with higher levels of leptin and C-reactive protein (CRP) appearing protective in premenopausal women but associated with increased risk in postmenopausal women. The opposing effects were particularly evident for leptin and CRP, which showed 11-17% lower breast cancer risk in premenopausal women but 10-16% higher risk in postmenopausal women, and these associations were influenced by body weight. These findings suggest that inflammation and obesity may affect breast cancer development through different biological mechanisms before and after menopause, highlighting the importance of considering menopausal status when assessing breast cancer risk factors.

Effects of endocrine disrupting chemicals, blood metabolome, and epigenetics on breast cancer risk: A multi-dimensional mendelian randomization study.

Song et al,

2025

Ecotoxicol Env Saf

A Mendelian randomization study using genetic data from European populations found that specific endocrine-disrupting chemicals (EDCs) were causally associated with different breast cancer subtypes: n-butyl paraben (n-BuP) increased Luminal A risk, mono-methyl phthalate decreased Luminal B risk, and mono-iso-butyl phthalate (MiBP) increased triple-negative breast cancer risk. Mediation analysis revealed that blood metabolites—including caffeic acid sulfate and caffeine metabolism ratios—partially explained the n-BuP effect on Luminal A, while methylsuccinate mediated the MiBP effect on triple-negative cancer, and epigenetic analysis identified specific DNA methylation sites associated with EDC exposure and breast cancer risk. These findings provide the first genetic evidence suggesting causal relationships between specific EDC exposures and breast cancer subtypes through distinct metabolic and epigenetic pathways, identifying potential biomarkers for early detection and highlighting the heterogeneous effects of different EDCs on breast cancer biology—underscoring the need for chemical-specific and subtype-specific prevention strategies rather than treating all EDCs or breast cancers as uniform entities.

The mediating roles of anthropo-metabolic biomarkers on the association between beverage consumption and breast cancer risk.

Lin et al,

2025

Nutr J

A prospective cohort study of 13,567 Chinese women followed for nearly 15 years found that consuming one or more servings of sugar-sweetened beverages (SSBs) per week was associated with a 58% increased breast cancer risk compared to consuming less than one serving weekly. The association was partly mediated by body mass index (4.2%) and uric acid (18.8%), with genetic analyses identifying additional metabolic mediators including cholesterol and fatty acid ratios accounting for small portions of the effect. Interestingly, higher soy milk consumption (3-6 portions weekly) was associated with a 69% reduced breast cancer risk, while dairy milk showed a non-significant trend toward increased risk, and no associations were found for juice, coffee, tea, or alcohol, suggesting that reducing SSB consumption and addressing the associated metabolic disruptions could be effective breast cancer prevention strategies.

Correlation between gut microbiota dysbiosis, metabolic syndrome and breast cancer.

Abdelqader et al,

2025

Sci Rep

A study of 50 breast cancer patients and 50 healthy women found that 60% of breast cancer patients had metabolic syndrome (a cluster of conditions including high blood pressure, blood sugar, and cholesterol) compared to 40% of healthy controls, and breast cancer patients had significantly lower levels of beneficial gut bacteria—specifically Lactobacillus and Bifidobacterium. These beneficial bacteria normally help protect against disease and regulate the immune system, suggesting their depletion may play a role in breast cancer development. The findings support a connection between metabolic health, gut bacteria composition, and breast cancer risk, pointing to potential new avenues for cancer prevention through dietary or probiotic interventions, though more research is needed.

Exposure to air pollutants and breast cancer risk: mediating effects of metabolic health biomarkers in a nested case-control study within the E3N-Generations cohort.

Mercoeur et al,

2024

Breast Cancer Res

A nested case-control study within the French E3N-Generations cohort examined 523 breast cancer cases and 523 matched controls to investigate whether thirteen metabolic health biomarkers mediate the relationship between exposure to three air pollutants (nitrogen dioxide, PCB153, and benzo[a]pyrene) and breast cancer risk. The study found that benzo[a]pyrene exposure was associated with a significant 2.32-fold increased breast cancer risk (highest vs. lowest quartile), PCB153 showed inconsistent positive associations, and nitrogen dioxide showed no association; among biomarkers, estradiol was associated with increased breast cancer risk (OR = 1.22 per SD). Four-way decomposition mediation analysis revealed suggestive evidence that albumin, HDL and LDL cholesterol, parathormone, and estradiol may partially mediate the associations between all three pollutants and breast cancer risk, though findings were limited by statistical power. These results provide preliminary mechanistic insights suggesting that air pollutants may influence breast cancer risk through alterations in metabolic biomarkers—particularly lipid metabolism and hormone regulation—though larger studies are needed to confirm these pathways and establish the clinical significance of these mediating effects in the relationship between environmental exposures and breast cancer development.

Edodes Cultured Extract Regulates Immune Stress During Puberty and Modulates MicroRNAs Involved in Mammary Gland Development and Breast Cancer Suppression.

Yasavoli-Sharahi et al,

2024

Cancer Med

A mouse study found that exposure to bacterial toxins (lipopolysaccharides or LPS) during puberty—a critical period for breast development—caused lasting inflammation and changes in gene expression that increased breast cancer risk later in life. Researchers discovered that a prebiotic supplement derived from shiitake mushrooms (AHCC) could counteract these harmful effects by reducing inflammation, regulating immune signaling molecules, and blocking cancer-promoting gene activity in mammary tissue. The findings suggest that gut health and inflammation during puberty may influence long-term breast cancer risk, and that dietary interventions like prebiotics might offer a preventive strategy, though human studies are needed to confirm these results.

Environmental cadmium exposure facilitates mammary tumorigenesis via reprogramming gut microbiota-mediated glutamine metabolism in MMTV-Erbb2 mice.

Yue et al,

2023

Sci Total Environ

In a transgenic mouse model (MMTV-Erbb2) that naturally develops mammary tumors, mice given oral cadmium (3.6 mg/L in drinking water for 23 weeks) developed palpable tumors significantly earlier and showed accelerated tumor growth compared with unexposed controls. Cadmium exposure increased the proliferation marker Ki-67, enhanced focal necrosis and new blood vessel formation in mammary tumors, and triggered greater intratumoral glutamine metabolism. Notably, disrupting gut microbiota with antibiotics delayed tumor onset and reduced tumor weight, implicating gut-microbiome–mediated metabolic reprogramming in cadmium-driven mammary tumorigenesis.

Microbial Alterations and Risk Factors of Breast Cancer: Connections and Mechanistic Insights.

Parida et al,

2020

Cells

A comprehensive review reveals that imbalanced gut and body microbiomes are linked to nearly all established breast cancer risk factors—including obesity, aging, periodontal disease, alcohol intake, reproductive history, and elevated estrogen levels—suggesting that microbial dysbiosis may itself be an important independent risk factor. The altered bacteria can promote cancer through multiple mechanisms: producing harmful metabolic byproducts, changing how the body processes medications and environmental chemicals, disrupting immune system function, and affecting how well cancer treatments work. These findings suggest that maintaining a healthy microbiome through diet, lifestyle, or therapeutic interventions could potentially reduce breast cancer risk and improve treatment outcomes, representing a promising new frontier in breast cancer prevention and management.

The Gut Microbiota: A Potential Gateway to Improved Health Outcomes in Breast Cancer Treatment and Survivorship.

Sampsell et al,

2020

Int J Mol Sci

The gut microbiome—trillions of bacteria living in the digestive tract—appears to influence breast cancer risk, treatment effectiveness, and likelihood of recurrence through its effects on metabolism, hormones, immune function, and brain signaling. While cancer treatments can disrupt the gut microbiome and contribute to negative side effects, research shows that the microbiome can be positively modified through diet, probiotic and prebiotic supplements, and exercise. This review synthesizes current evidence on the gut-breast cancer connection and highlights practical strategies for improving gut health that may lead to better treatment outcomes, fewer side effects, and improved overall wellbeing for breast cancer patients.

Parabens and their effects on the endocrine system.

Nowak et al,

2018

Mol Cell Endocrinol

A review examining parabens—one of the most widely used preservatives worldwide in foods, cosmetics, and pharmaceuticals—found that these easily absorbed chemicals are classified as endocrine-disrupting chemicals (EDCs) that can disrupt hormonal homeostasis and cause multidirectional health implications affecting body fitness and function. The review summarizes current literature on paraben properties, occurrence, metabolism, and particularly their influence on the human endocrine system, emphasizing the importance of assessing their safety given their ubiquitous use and absorption. With parabens now recognized as EDCs capable of disrupting endocrine function, the authors highlight concerns about widespread population exposure through everyday consumer products and the need for precise assessment of their health impacts on human physiology.

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