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Neighborhood Environment, DNA Methylation, and Presence of Crown-Like Structures of the Breast.

Harris et al,

2025

JAMA Netw Open

In a cross-sectional study involving Black and White women participating in the NCI Maryland Breast Cancer Study, the investigators examined associations between neighborhood-level deprivation, air pollution (PM₂.₅) and presence of breast tissue crown-like structures (CLS-B) plus DNA methylation patterns. Higher PM₂.₅ exposure and greater neighborhood deprivation were associated with increased odds of having CLS-B (OR for PM₂.₅ 2.32, 95% CI: 1.12–4.78). The findings point to how socio-environmental disadvantage and pollution may influence breast adipose inflammation and epigenetic changes linked to cancer risk.

The role of di-(2-ethylhexyl) phthalate in cancer initiation and progression: Mechanisms and health implications.

Zhou et al,

2025

Sci Total Environ

This review examines the relationship between DEHP (a common plastic additive) and cancer development, noting that while epidemiological studies suggest a link between DEHP exposure and increased cancer risk, the specific mechanisms need further clarification. The research shows that DEHP influences multiple aspects of cancer biology, including cell growth, spread, and drug resistance, through various molecular pathways involving hormone receptors, inflammation, and genetic modifications. DEHP’s carcinogenic effects operate through complex mechanisms including PI3K/AKT signaling, estrogen receptor activation, and oxidative stress. Understanding these molecular pathways could help develop targeted strategies to prevent and treat cancers associated with DEHP exposure.

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.

The endoplasmic reticulum-mitochondrial crosstalk involved in nanoplastics and di(2-ethylhexyl) phthalate co-exposure induced the damage to mouse mammary epithelial cells.

Wang et al,

2025

Environ Pollut

This study examined the combined toxic effects of nanoplastic particles (NPs) and DEHP plasticizer on mouse mammary epithelial cells, finding that co-exposure caused severe cell death (pyroptosis), inflammation, and oxidative stress. The researchers discovered that the combination damaged mitochondria and increased endoplasmic reticulum stress, leading to disrupted cellular energy production and membrane integrity. Notably, co-exposure enhanced communication between cellular organelles (ER-mitochondria crosstalk), involving increased calcium levels and expanded contact areas between these structures. The findings reveal new molecular mechanisms by which plastic particles and plasticizers can work together to damage mammary gland tissue, providing insights into potential breast health risks from environmental plastic pollution.

Multilevel Stressors and Systemic and Tumor Immunity in Black and White Women With Breast Cancer.

Harris et al,

2025

JAMA Netw Open

A cross-sectional study of 121 Black and White women with breast cancer found that chronic stressors—including perceived stress, inadequate social support, discrimination, and neighborhood deprivation—were associated with harmful immune and tumor changes, with particularly pronounced effects in Black women who also lived in significantly more socioeconomically deprived neighborhoods. Higher stress, discrimination, and neighborhood deprivation were linked to increased systemic inflammation, immune-suppressive tumor environments (including tumor-promoting M2 macrophages), and elevated tumor mutational burden, while greater social support was associated with beneficial immune-stimulatory changes including increased natural killer cells in breast tissue. Black women showed distinct stress-related immunologic signatures including enhanced chemotaxis, immune suppression at the systemic level, and increased tumor-associated myeloid cells, suggesting that chronic psychosocial and environmental stressors may biologically contribute to breast cancer disparities by creating a pro-tumorigenic immune environment—findings that underscore the urgent need for interventions addressing social determinants of health as cancer prevention strategies.

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 endocrine disrupting chemical-DEHP exposure-provoked biotoxicity about microbiota-gut-mammary axis in lactating mice via multi-omics technologies.

Xu et al,

2024

Environ Int

A study in mice found that exposure to DEHP—a common chemical used to make plastics flexible—disrupts the gut-mammary connection, causing changes in gut bacteria, intestinal inflammation, and direct damage to mammary (breast) tissue that could impair milk production. DEHP altered gut microbiome composition (increasing some bacteria while decreasing others), changed blood metabolite levels, and its breakdown product (MEHP) triggered cell death in mammary tissue through multiple pathways. These findings raise concerns about DEHP exposure from plastics affecting both human breast health and dairy production in livestock, while identifying potential therapeutic targets to counteract the chemical’s harmful effects on the gut-breast axis.

Linking Physical Activity to Breast Cancer via Inflammation, Part 2: The Effect of Inflammation on Breast Cancer Risk.

Lou et al,

2023

Cancer Epidemiol Biomark Prev

A systematic review and meta-analysis of 34 observational studies and 3 Mendelian randomization studies found that women with the highest levels of C-reactive protein (CRP)—a marker of systemic inflammation—had a 13% increased breast cancer risk compared to those with the lowest levels, though the quality of evidence was rated as very low to moderate. While adiponectin showed a protective association (24% reduced risk), this finding was not supported by genetic evidence from Mendelian randomization studies, and there was little evidence that other inflammatory markers like TNFα and IL-6 affected breast cancer risk. These findings suggest that while chronic low-grade inflammation measured by CRP may modestly increase breast cancer risk, the overall role of inflammation in breast cancer development remains unclear, with limited support beyond CRP—highlighting the need for higher-quality prospective studies and mechanistic research to clarify whether inflammation is truly causal or merely a marker of other underlying processes that drive breast carcinogenesis.

The impact of social and environmental factors on cancer biology in Black Americans.

Lord et al,

2023

Cancer Causes Control

A review examining how low socioeconomic status (SES) contributes to early chronic disease onset and reduced life expectancy found that neighborhood-level factors—including environmental pollutants, deprivation, social isolation, structural racism, and discrimination—create chronic life stress that affects molecular processes like DNA methylation, inflammation, and immune response, contributing to more aggressive tumor biology, particularly in Black Americans. Despite decades of research showing associations between neighborhood factors and cancer outcomes in marginalized communities, the biological mechanisms linking SES to cancer disparities remain poorly understood, though emerging evidence suggests chronic stress pathways may play a central role. The authors summarize current methods for measuring neighborhood-level deprivation, discrimination, and structural racism in cancer disparities research and recommend adopting a multi-faceted intersectional approach to reduce cancer health inequities and develop effective interventions promoting health equity.

Intestinal Vitamin D receptor protects against extraintestinal breast cancer tumorigenesis.

Zhang et al,

2023

Gut Microbes

A mouse study revealed that Vitamin D receptor (VDR) deficiency in the gut lining leads to bacterial imbalance (dysbiosis), increased intestinal permeability (“leaky gut”), and bacterial migration to breast tissue, significantly increasing breast tumor formation. Mice lacking intestinal VDR developed larger and more numerous breast tumors, with harmful bacteria like Streptococcus found in the tumor tissue, while beneficial bacteria that normally protect against cancer were depleted. However, treatment with butyrate (a beneficial bacterial byproduct) or the probiotic Lactobacillus plantarum reduced breast tumors by restoring gut barrier function and reducing inflammation, demonstrating a direct gut-breast axis. These findings suggest that maintaining gut health through adequate Vitamin D, beneficial bacteria, and a healthy microbiome may be a promising strategy for breast cancer prevention, though human studies are needed to confirm these results.

Redlining-associated methylation in breast tumors: the impact of contemporary structural racism on the tumor epigenome.

Miller-Kleinhenz et al,

2023

Front Oncol

A study of 80 Black and White women with breast cancer at Emory University Hospitals (2008-2017) examined associations between contemporary neighborhood redlining—a structural racism measure derived from Home Mortgage Disclosure Act data—and DNA methylation patterns in breast tumor tissue. Contemporary redlining was significantly associated with aberrant methylation at 5 CpG sites (FDR<0.10) in genes implicated in breast carcinogenesis, inflammation, immune function, and stress response (ANGPT1, PRG4), with additional top sites showing interaction by ER status and association with mortality; redlining was also associated with epigenetic age acceleration (β=5.35; 95% CI: 0.30-10.4 by Hannum metric). These novel findings suggest that structural racism—manifested through discriminatory housing policies leading to inequitable social and environmental exposures—may biologically embed in the breast tumor epigenome through altered DNA methylation patterns, potentially contributing to documented racial disparities in breast cancer outcomes and highlighting the need for further research on epigenetic mechanisms linking neighborhood-level structural racism to cancer prognosis.

Dietary Inflammatory Index and risk of breast cancer: evidence from a prospective cohort of 67,879 women followed for 20 years in France.

Hajji-Louati et al,

2023

Eur J Nutr

A large prospective cohort study of 67,879 French women followed for 21 years found that higher dietary inflammatory potential was associated with a 4% increased breast cancer risk per standard deviation increase in DII score, with women in the highest versus lowest quintile showing a 13% increased risk in a linear dose-response relationship. The association was slightly stronger among non-smokers (6% increased risk per standard deviation) and low alcohol consumers (5% increased risk per standard deviation), suggesting that inflammatory diet effects may be most pronounced in women without other pro-inflammatory exposures. These findings from one of the largest and longest prospective studies provide strong evidence that promoting anti-inflammatory dietary patterns—rich in fruits, vegetables, whole grains, legumes, nuts, and fish while limiting processed foods, red meat, refined carbohydrates, and saturated fats—could contribute meaningfully to breast cancer prevention as part of comprehensive public health strategies.

Association of Empirically Derived Food-Based Inflammatory Potential of the Diet and Breast Cancer: A Hospital-Based Case-Control Study.

Ghanbari et al,

2022

Clin Breast Cancer

A case-control study of 150 Iranian women with newly diagnosed breast cancer matched with 150 controls found that women consuming the most pro-inflammatory diets (highest quartile of food-based dietary inflammatory index) had a 138% increased breast cancer risk compared to those with the least inflammatory diets, with the association remaining significant (180% increased risk) after adjusting for confounding factors. The food-based empirical dietary inflammatory index (FDII), which scores dietary patterns based on 27 pre-defined food groups according to their inflammatory potential, showed a clear dose-response relationship with breast cancer risk across quartiles. These findings from a Middle Eastern population reinforce that dietary patterns promoting systemic inflammation substantially increase breast cancer risk, and suggest that practical, food-based dietary modifications—emphasizing anti-inflammatory whole foods like fruits, vegetables, whole grains, legumes, nuts, and fish while limiting pro-inflammatory processed foods, red meat, and refined carbohydrates—could be an effective and culturally adaptable breast cancer prevention strategy.

Dietary inflammatory index and breast cancer risk: an updated meta-analysis of observational studies.

Hayati et al,

2022

Nutr Cancer

An updated meta-analysis of 21 studies including over 346,000 participants found that the most pro-inflammatory diets were associated with a 16% increased breast cancer risk overall, with particularly strong associations among postmenopausal women (13% increased risk), obese women with BMI ≥30 kg/m² (35% increased risk), and populations in developing countries (79% increased risk). The analysis revealed important methodological influences on effect estimates, with stronger associations observed in case-control studies (50% increased risk), studies using hospital-based controls (111% increased risk), and cohort studies with prolonged follow-up (13% increased risk). These findings not only confirm that pro-inflammatory dietary patterns increase breast cancer risk but also demonstrate that the magnitude of association varies substantially by population characteristics and study design, with obesity and postmenopausal status appearing to amplify the carcinogenic effects of inflammatory diets—suggesting that anti-inflammatory dietary interventions may be particularly beneficial for overweight/obese postmenopausal women and populations in developing countries where rapid dietary transitions toward processed, inflammatory foods are occurring.

Inflammatory potential of the diet and risk of breast cancer in the European Investigation into Cancer and Nutrition (EPIC) study.

Castro-Espin et al,

2021

Eur J Epidemiol

A large prospective study of 318,686 European women followed for 14 years found that consuming a pro-inflammatory diet was associated with a 4% increased breast cancer risk per standard deviation increase in inflammatory diet score, with women in the most pro-inflammatory diet group showing a 12% increased risk compared to those consuming the least inflammatory diets. The association was particularly strong in premenopausal women (8% increased risk per standard deviation), and notably, the pro-inflammatory diet effect was independent of body mass index, physical activity, and alcohol consumption, suggesting that dietary inflammation contributes to breast cancer risk through pathways distinct from these other established risk factors. The consistent associations across all hormone receptor-defined breast cancer subtypes suggest that dietary inflammation may promote breast cancer through non-hormonal mechanisms, reinforcing the importance of anti-inflammatory dietary patterns—rich in fruits, vegetables, whole grains, and omega-3 fatty acids while limiting processed foods, red meat, and refined carbohydrates—as a modifiable strategy for breast cancer prevention across all women, particularly those still premenopausal.

Strong association between the dietary inflammatory index(DII) and breast cancer: a systematic review and meta-analysis.

Chen et al,

2021

Aging

A meta-analysis of 14 studies including 312,885 women found that those consuming the most pro-inflammatory diets had a 37% increased breast cancer risk compared to women with the most anti-inflammatory diets. The association was significant in both premenopausal women (87% increased risk) and postmenopausal women (23% increased risk), with notably stronger effects observed in younger women. These findings suggest that dietary patterns promoting chronic inflammation are an independent risk factor for breast cancer across all ages, and that dietary interventions focused on anti-inflammatory foods—such as fruits, vegetables, whole grains, and omega-3 fatty acids—could be an important prevention strategy, particularly for premenopausal women who showed the strongest association.

The Inflammatory Potential of Diet is Associated with Breast Cancer Risk in Urban Argentina: A Multilevel Analysis.

Niclis et al,

2021

Nutr Cancer

A case-control study of 317 breast cancer patients and 526 controls in Córdoba, Argentina found that women consuming the most pro-inflammatory diets (highest Dietary Inflammatory Index scores) had a 34% increased breast cancer risk compared to those with the least inflammatory diets. The association was markedly stronger among overweight and obese women, who showed a 98% increased risk with pro-inflammatory diets, and the effect was amplified in more urbanized areas compared to rural settings. These findings suggest that dietary patterns promoting systemic inflammation contribute to breast cancer risk, particularly in combination with obesity and urban lifestyle factors, highlighting the potential for dietary interventions focused on anti-inflammatory foods as a prevention strategy, especially in overweight women living in urban environments.

Is the skin microbiota a modifiable risk factor for breast disease?: A systematic review.

Wang et al,

2021

Breast

A systematic review of 22 studies found that breast skin harbors distinct bacterial communities, with imbalances in these bacteria—particularly certain Staphylococcus species—linked to breast cancer, metastases, inflammation, and implant complications. The research suggests bacteria can migrate from skin into underlying breast tissue through milk ducts, damaged skin barriers, or nipple fluid, potentially contributing to disease development. These findings indicate that breast skin bacteria may be a modifiable risk factor for breast diseases, opening possibilities for using probiotics, antimicrobials, or microbiome-based diagnostics as new tools for prevention, diagnosis, and treatment of breast conditions.

Direct and indirect associations between dietary magnesium intake and breast cancer risk.

Huang et al,

2019

Sci Rep

A case-control study of 1,050 breast cancer cases and 1,229 controls in which inflammatory markers (C-reactive protein and interleukin-6) were measured in 322 randomly selected case-control pairs examined whether dietary magnesium intake affects breast cancer risk directly and indirectly through inflammation. Higher magnesium intake was associated with 20% lower breast cancer risk (adjusted OR = 0.80; 95% CI: 0.65-0.99), while elevated CRP levels were associated with 43% increased risk (adjusted OR = 1.43; 95% CI: 1.02-2.01), though IL-6 showed no association with breast cancer. Path analysis revealed that dietary magnesium intake reduces breast cancer risk through two pathways: a direct protective effect and an indirect effect by lowering CRP levels, an inflammatory marker. These findings suggest that magnesium’s protective role against breast cancer operates both through anti-inflammatory mechanisms (by reducing systemic inflammation as measured by CRP) and through other direct biological pathways, highlighting the potential importance of adequate dietary magnesium intake for breast cancer prevention and the role of chronic inflammation in breast cancer development.

Meta-analysis of the association between the dietary inflammatory index (DII) and breast cancer risk.

Wang et al,

2019

Eur J Clinic Nutr

A meta-analysis of seven observational studies including 319,993 participants found that women consuming the most pro-inflammatory diets (highest DII scores) had a 25% increased breast cancer risk compared to those with the least inflammatory diets, with particularly strong associations observed in postmenopausal women (15% increased risk) and hormone receptor-negative breast cancers (36% increased risk). The association varied by geography, showing dramatically elevated risk in Asian populations (130% increase) and more modest effects in European populations (26% increase), while case-control studies showed stronger associations (68% increase) than cohort studies. These findings reinforce that dietary patterns promoting chronic systemic inflammation—typically characterized by high intake of refined carbohydrates, red/processed meats, and trans fats with low intake of fruits, vegetables, and omega-3 fatty acids—contribute meaningfully to breast cancer risk, supporting dietary interventions focused on anti-inflammatory foods as a practical prevention strategy.

The Impact of Obesity on Breast Cancer.

Argolo et al,

2018

Curr Oncol Rep

Obesity is now recognized as a leading preventable cause of cancer, particularly postmenopausal estrogen receptor-positive breast cancer, and is associated with worse outcomes across all breast cancer subtypes. Multiple interconnected mechanisms link obesity to breast cancer, including elevated estrogen levels, altered hormone-like molecules from fat tissue (leptin and adiponectin), disrupted insulin signaling, changes in gut bacteria, and chronic inflammation throughout the body. Understanding these complex pathways could lead to new prevention and treatment strategies to reduce the growing burden of obesity-related breast cancers worldwide.

Dietary Inflammatory Potential Score and Risk of Breast Cancer: Systematic Review and Meta-analysis.

Zahedi et al,

2018

Clinic Breast Cancer

A systematic review and meta-analysis of 9 studies including 296,102 participants found that higher dietary inflammatory potential was associated with a 14% increased breast cancer risk overall, though the association varied by study design with case-control studies showing stronger effects (63% increased risk, not statistically significant) than cohort studies (4% increased risk, not significant). The pooled analysis across all study types showed a significant positive association between pro-inflammatory diets and breast cancer, suggesting that dietary modifications to reduce inflammatory potential could meaningfully reduce breast cancer risk. These findings reinforce that chronic low-grade inflammation driven by diet—characterized by high intake of refined carbohydrates, red and processed meats, and trans fats with low consumption of anti-inflammatory foods like fruits, vegetables, whole grains, and omega-3 fatty acids—contributes to breast carcinogenesis, supporting dietary pattern interventions focused on anti-inflammatory foods as an accessible and modifiable prevention strategy for women.

Dietary Inflammatory Index and Odds of Breast Cancer in a Case-Control Study from Iran.

Jalali et al,

2018

Nutr Cancer

A case-control study of 136 breast cancer patients and 272 controls in Iran found that women consuming the most pro-inflammatory diets (highest quartile of DII scores) had a 164% increased breast cancer risk compared to those with the least inflammatory diets, with the association particularly striking among premenopausal women who showed a 451% increased risk. No association was detected in postmenopausal women, contrasting with findings from other studies that have typically shown stronger effects in postmenopausal populations. These findings suggest that pro-inflammatory dietary patterns may be especially harmful during premenopausal years when breast tissue is more metabolically active and hormone-responsive, highlighting the potential importance of anti-inflammatory dietary interventions—emphasizing whole grains, fruits, vegetables, legumes, nuts, and fish while limiting processed foods, red meat, and refined carbohydrates—as a targeted prevention strategy for younger women at risk of breast cancer.

Environmental immune disruptors, inflammation and cancer risk.

Thompson et al,

2015

Carcinogenesis

A review examining the intersection of environmental toxicants, immune function, and cancer development argues that common chemicals like bisphenol A, atrazine, and phthalates can disrupt the delicate balance between pro- and anti-inflammatory immune responses, potentially contributing to tumor development through immune system dysfunction. The authors highlight that while the role of immunity in cancer is well-established, research on how environmental chemicals affect immune cells as co-factors in cancer causation remains underdeveloped compared to studies on autoimmunity and allergies. The review calls for increased research using systems biology approaches to better understand how chemical exposures disturb inflammatory pathways and immune molecules involved in tumor-associated inflammation, arguing that chemically induced immune perturbations represent an important but understudied mechanism of environmental carcinogenesis.

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