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The impact of cadmium exposure on breast cancer risk: Exploring dose-response relationships and mediating effects.

Lu et al,

2025

Ecotoxicol Environ Saf

This study examined the link between cadmium (Cd) exposure and breast cancer risk using data from nearly 6,000 participants and a meta-analysis of 20 studies. The researchers found that higher cadmium levels significantly increased breast cancer risk, with the strongest association in estrogen receptor-positive (ER+) breast cancer subtypes, and identified glycated hemoglobin (HbA1c, a marker of blood sugar control) as a potential mechanism linking cadmium exposure to cancer development. The findings suggest that cadmium, an endocrine-disrupting metal found in the environment, may contribute to breast cancer through metabolic disruption. These results highlight the importance of reducing cadmium exposure and understanding how environmental toxins interact with metabolic health to influence cancer risk.

Multiple xenoestrogen air pollutants and breast cancer risk: Statistical approaches to investigate combined exposures effect.

Amadou et al,

2024

Environ Pollut

A French study of over 10,000 women found that combined exposure to a mixture of four hormone-disrupting air pollutants (benzo[a]pyrene, cadmium, dioxin, and PCB153) was associated with an approximately 10-11% increased risk of breast cancer. Using advanced statistical methods that account for simultaneous exposure to multiple pollutants rather than examining each separately, researchers found that benzo[a]pyrene, cadmium, and PCB153 showed the strongest individual contributions to increased breast cancer risk within the mixture. This research provides important evidence that the cumulative effect of multiple air pollutants acting together on hormone pathways may be a significant risk factor for breast cancer development.

Multi-pollutant exposure profiles associated with breast cancer risk: A Bayesian profile regression analysis in the French E3N cohort.

Giampiccolo et al,

2024

Environ Int

A comprehensive French study of over 10,000 women examined exposure to eight different air pollutants simultaneously and identified that women exposed to high levels of nitrogen dioxide (NO₂), particulate matter, and PCB153 had a 38-61% increased risk of breast cancer compared to women with low pollution exposure. Using advanced statistical modeling that groups women by their combined pollution exposure patterns rather than examining pollutants individually, researchers found that specific combinations of high pollutant exposures were strongly associated with elevated breast cancer risk. This study provides important evidence that the combined “cocktail effect” of multiple air pollutants, particularly traffic-related pollution (NO₂) and industrial chemicals (PCB153), may significantly increase breast cancer risk beyond what individual pollutants cause alone.

Urinary Concentrations of Endocrine-Disrupting Metals and Prevalent Breast Cancer in US Women.

Bell et al,

2023

Biol Trace Elem Res

This cross-sectional analysis from the 2007–2016 National Health and Nutrition Examination Survey (NHANES) explored the relationship of urinary concentrations of heavy metals and breast cancer. 3,352 U.S. women (aged 20 or older) in the were included in the analysis. 106 reported a history of breast cancer (weighted prevalence ~ 3.1%). Researchers measured urinary concentrations of heavy metals — cadmium, lead, and mercury — corrected for creatinine, then applied multivariate logistic regression to assess associations with prevalent breast cancer. They found that women in the highest quartile of urinary lead (≥ 0.71 µg/g creatinine) had significantly elevated odds of prior breast cancer (OR = 2.95, 95% CI: 1.13–7.70) compared with those in the lowest quartile; by contrast, urinary cadmium and mercury showed no statistically significant associations. The findings suggest that among common endocrine-disrupting metals, lead exposure — as measured by urinary biomarkers — may be linked with increased breast cancer prevalence in U.S. women.

Endocrine-disrupting chemicals (EDCs) and cancer: new perspectives on an old relationship.

Modica et al,

2023

J Endocrinol Invest

A comprehensive literature review examining environmental endocrine-disrupting chemicals (EDCs) and hormone-related cancers concludes that several EDCs can be definitively classified as carcinogenic, including dioxin and cadmium for breast and thyroid cancer, arsenic and dioxin for prostate cancer, and organochlorines for testicular cancer. The review highlights that fetuses and newborns are most vulnerable to endocrine disruption, with adverse effects potentially manifesting at different ages throughout life, making it difficult to assess the full health impact of EDC exposure. The authors emphasize that EDCs represent a major environmental health issue requiring effective prevention policies, increased public awareness, and protective measures—particularly for pregnant women—along with standardized testing criteria to evaluate the carcinogenic potential of new chemicals before they enter widespread use.

Long-term exposure to airborne metals and risk of cancer in the French cohort Gazel.

Lequy et al,

2023

Environ Int

This cohort study examined associations of metals to multiple cancer sites. Participants were from a cohort study of worker from the French national energy company who lived in semi-urban or rural locations. The researchers estimated metal exposures from moss biomonitoring (part of a larger effort to measure air pollution). Estimated exposures to metals were associated any cancer (bladder, lung, breast or prostate), but no estimated exposures were associated with breast cancer alone. Some estimates appraoched HR >1 for breast cancer.

Chronic long-term exposure to cadmium air pollution and breast cancer risk in the French E3N cohort.

Amadou et al,

2020

Cancer Epiemiol

A French study of over 8,000 women found no overall association between long-term airborne cadmium exposure and breast cancer risk, but unexpectedly discovered that higher cadmium exposure was associated with a 32-38% decreased risk of estrogen receptor-negative (ER-) breast cancers. This finding contradicts the hypothesis that cadmium increases breast cancer risk through its estrogen-like effects, and instead suggests cadmium may have different biological effects depending on the hormone receptor status of tumors. These surprising results indicate that cadmium’s relationship with breast cancer is more complex than previously thought and may involve mechanisms beyond its known estrogen-mimicking properties, requiring further research to understand why it might protect against hormone receptor-negative tumors.

Cadmium Exposure and Risk of Breast Cancer by Histological and Tumor Receptor Subtype in White Caucasian Women: A Hospital-Based Case-Control Study.

Strumylaite et al,

2019

Int J Mol Sci

This case-control study of 509 breast cancer patients and 1,170 controls in examined whether cadmium exposure—a metalloestrogen that mimics estrogen—is associated with specific breast cancer subtypes based on urinary cadmium levels. Women with the highest cadmium levels (>0.33 μg/g creatinine) had 53% increased odds of ductal breast cancer (OR=1.53, 95% CI: 1.15-2.04) compared to those with the lowest levels, with the strongest associations observed for hormone receptor-positive tumors: 34% increased odds for ER+ cancers (OR=1.34, 95% CI: 1.14-1.59), 33% for PR+ cancers (OR=1.33, 95% CI: 1.09-1.61), and 35% for ER+/PR+ cancers (OR=1.35, 95% CI: 1.11-1.65). The study found significant associations with HER2-negative cancers, with the strongest link for ER+/PR+/HER2- breast cancers, supporting the hypothesis that cadmium acts as an endocrine disruptor. These findings provide evidence that cadmium exposure is specifically associated with hormone receptor-positive and HER2-negative breast cancer risk, independent of tumor type, suggesting cadmium’s estrogenic properties may contribute to hormone-driven breast cancers.

Dietary cadmium and risk of breast cancer subtypes defined by hormone receptor status: A prospective cohort study.

Grioni et al,

2019

Cancer Epidemiol

A 22-year Italian study following nearly 9,000 women found that those with the highest dietary cadmium intake (a toxic metal found in foods like grains, vegetables, and shellfish) had a 54% increased breast cancer risk compared to those with the lowest intake, with even stronger associations in premenopausal women (73% increased risk). Cadmium—classified as a proven human carcinogen—enters the food supply primarily through contaminated soil and water, with diet being the main exposure source for non-smokers at an average intake of about 8 micrograms per day in this population. The increased risk was consistent across all breast cancer subtypes regardless of hormone receptor status, supporting cadmium as a dietary risk factor for breast cancer and highlighting the need for strategies to reduce cadmium levels in the food supply through soil remediation and crop selection.

Metallic Air Pollutants and Breast Cancer Risk in a Nationwide Cohort Study.

White et al,

2019

Epidemiol

A large US study of nearly 51,000 women found that exposure to airborne toxic metals, particularly mercury, cadmium, and lead, was associated with increased postmenopausal breast cancer risk, with mercury showing the strongest effect at 30% increased risk for the highest exposure levels. When examining the combined effect of 10 different airborne metals together, the mixture was associated with elevated postmenopausal breast cancer risk, with mercury, lead, and cadmium contributing most to this increased risk. These findings suggest that environmental exposure to toxic metals through air pollution may be an important and underrecognized risk factor specifically for breast cancer in postmenopausal women.

Heavy-metal associated breast cancer and colorectal cancer hot spots and their demographic and socioeconomic characteristics.

Tomlinson et al,

2024

Cancer Causes Control

A population-based study using Kentucky cancer registry data (77,637 breast cancer and 56,598 colorectal cancer cases) found that higher ambient air concentrations of carcinogenic metals—cadmium, arsenic, nickel, and chromium(VI)—were associated with increased odds of residing in breast and colorectal cancer hotspots, independent of individual risk factors including age, race, smoking, and neighborhood socioeconomic characteristics. Cancer hotspot populations were disproportionately Black and exhibited markers of lower socioeconomic status, and importantly, the metal-cancer associations persisted even after adjusting for these factors, suggesting environmental metal exposure is an independent contributor to geographic cancer clustering. These findings provide evidence that historically marginalized communities face disproportionate exposure to carcinogenic metals through environmental pollution, likely contributing to cancer disparities, and underscore the urgent need for environmental justice interventions including stricter air quality regulations, cleanup of contaminated sites, and individual-level exposure assessments to fully understand how metal exposures drive cancer inequities in vulnerable populations.

Ambient Air Pollution Exposure and Breast Cancer Risk Worldwide: A Systematic Review of Longitudinal Studies.

Tippila et al,

2024

Int J Environ Res Public Health

A systematic review of 25 epidemiological studies (2013-2022) found that seven out of eight investigated outdoor air pollutants showed significant associations with increased breast cancer risk, with benzo[a]pyrene showing the strongest relationship. The review found that 100% of studies examining nitrogen oxides (NOₓ), 83% of PM₂.₅ studies, 69% of nitrogen dioxide (NO₂) studies, and 43% of PM₁₀ studies demonstrated positive associations with breast cancer risk, with hazard ratios ranging from 1.05-1.56 and odds ratios from 1.03-1.86, while ozone and cadmium showed negative or no associations. These findings strengthen the evidence that outdoor air pollution—particularly traffic-related pollutants and fine particulate matter—contributes to breast cancer development, though the authors note that further research is needed to establish causal mechanisms, particularly through epigenetic pathways, and acknowledge that the review’s focus on English-language articles from developed countries may limit generalizability.

Cadmium exposure and risk of breast cancer: A meta-analysis.

Florez-Garcia et al,

2023

Environ Res

A meta-analysis of 17 epidemiological studies examining cadmium exposure and breast cancer risk found no statistically significant associations overall or when examining specific exposure routes separately (dietary cadmium or biomarker-based studies), with substantial heterogeneity between studies and no clear patterns by menopausal status. The inconclusive findings leave critical questions about whether specific exposure routes (occupational, air pollution, smoking) pose different risks than dietary intake or whether residual confounding by tobacco smoke constituents may influence observed associations. These results highlight the need for future research with better exposure assessment methods that can distinguish between different cadmium sources and routes of exposure, particularly occupational and environmental air pollution exposures that may be more relevant than diet for populations living near industrial areas where cadmium contamination is prevalent.

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.

Breast cancer and urinary metal mixtures in Mexican women.

Mérida-Ortega et al,

2022

Environ Res

A case-control study of 499 breast cancer patients and 499 controls in Northern Mexico found that women with breast cancer had distinct patterns of urinary metal exposure, with higher concentrations of tin and lower concentrations of vanadium, cobalt, and molybdenum compared to controls. Using principal component analysis to identify metal mixtures, researchers discovered two distinct exposure patterns with opposite breast cancer associations: a mixture containing chromium, nickel, antimony, aluminum, lead, and tin showed a 15% increased risk, while a mixture of molybdenum and cobalt showed a 44% reduced risk. This is the first study to identify specific urinary metal mixture profiles associated with breast cancer, highlighting that metals may interact synergistically or antagonistically rather than acting independently, and underscoring the critical need for mixture-based approaches in environmental health research—since real-world exposures involve multiple simultaneous contaminants whose combined effects may differ substantially from predictions based on individual metals alone—along with mechanistic studies to understand how metal interactions influence breast carcinogenesis.

Exposure to airborne cadmium and breast cancer stage, grade and histology at diagnosis: findings from the E3N cohort study.

Amadou et al,

2021

Sci Rep

A nested case-control study of 4,401 breast cancer cases and 4,401 matched controls from the French E3N cohort found no overall association between long-term airborne cadmium exposure and breast cancer stage or tumor grade, but identified a striking 240% increased risk of invasive tubular carcinoma (ITC)—a specific breast cancer subtype—among women in the highest versus lowest quintile of cadmium exposure. The dose-response analysis suggested a linear relationship between cadmium exposure and ITC risk specifically, though no associations were found for other histological subtypes or more advanced disease. These findings suggest that cadmium’s estrogenic properties may selectively promote certain breast cancer subtypes rather than broadly increasing all breast cancer risk, highlighting the importance of examining cancer heterogeneity in environmental exposure studies and raising concerns about air pollution from industrial sources, waste incineration, and fossil fuel combustion that release cadmium into the environment.

Cadmium exposure and risk of breast cancer: A dose-response meta-analysis of cohort studies.

Filippini et al,

2020

Environ Int

A systematic review and dose-response meta-analysis of 10 cohort studies found no clear association between cadmium exposure and breast cancer risk, whether assessed through dietary intake or urinary excretion levels, with all analyses showing non-significant results. Analysis restricted to postmenopausal women also showed no associations, and while data were insufficient to examine potential associations in specific subgroups defined by age, smoking status, or hormone receptor status, the overall evidence does not support cadmium as a breast cancer risk factor. The authors note that available data were too limited to rule out possible associations in selected vulnerable subgroups, highlighting the need for future studies with better exposure assessment and larger sample sizes to detect subgroup-specific effects if they exist.

Blood levels of cadmium and lead in relation to breast cancer risk in three prospective cohorts.

Gaudet et al,

2019

Int J Cancer

A meta-analysis of three nested case-control studies (CPS-II, EPIC-Italy, and NSHDS) including 1,435 breast cancer cases and 1,433 controls examined whether erythrocyte levels of cadmium and lead—both classified as carcinogens—were associated with breast cancer risk. Cadmium levels showed no association with breast cancer in the CPS-II cohort, inverse associations in the EPIC-Italy and NSHDS cohorts, and an overall inverse trend in the meta-analysis (continuous RR = 0.84; 95% CI 0.69-1.01), while large differences in lead distributions across studies prevented meta-analysis, and no individual study found associations between lead and breast cancer risk. These findings indicate that despite cadmium and lead being established carcinogens with persistent environmental presence and ubiquitous human exposure, circulating levels of these metals in adulthood were not associated with increased breast cancer risk in this large pooled analysis. The unexpected inverse association with cadmium observed in some cohorts requires further investigation to understand potential biological mechanisms or confounding factors.

Heavy metals and phthalate contamination in prenatal vitamins and folic acid supplements

Gardener et al.

2025

Environ Res

A study analyzing 156 commercially available prenatal vitamins, 19 folate/folic acid supplements, and 9 prescription prenatals found widespread contamination with heavy metals and phthalates: 83% of commercial prenatals contained detectable lead (15% exceeding California’s 0.5 μg/daily threshold), 73% contained cadmium, 25% contained DEHP, and 13% contained DBP, with higher contamination associated with calcium and iron content and caplet/capsule/tablet formulations. Prescription prenatals also showed contamination, with 7 of 9 containing detectable lead or cadmium and 33% exceeding the lead threshold, while folate/folic acid supplements showed lower contamination levels. These findings reveal that pregnant women—a population particularly vulnerable to environmental chemical exposures—are being exposed to lead, cadmium, and endocrine-disrupting phthalates through the very supplements intended to support healthy pregnancy. Since prenatal supplementation remains critical for fetal development, pregnant women should prioritize products with third-party verification seals (such as USP, NSF International, or ConsumerLab) which confirm label accuracy, purity, and manufacturing standards, and clear, enforceable regulations requiring frequent testing and strict contamination limits are urgently needed.

Heavy Metals and Trajectories of Anti-Müllerian Hormone During the Menopausal Transition

Ding, et al.

2024

J Clin Endocrinol Metab

A longitudinal study of 549 women with 2,252 repeated anti-Müllerian hormone (AMH) measurements over the 10 years preceding final menstrual period found that elevated arsenic levels were associated with a 32.1% decline in AMH concentrations and elevated mercury levels with a 40.7% decline over the decade, while elevated cadmium and mercury showed significant per-year declines of 9.0% and 7.3% respectively. The findings indicate that higher exposure to heavy metals—particularly arsenic, cadmium, and mercury—is correlated with accelerated depletion of ovarian reserve (remaining viable eggs) in women approaching menopause. This study suggests that environmental heavy metal exposure may contribute to earlier reproductive aging and diminished ovarian function.

Serum heavy metals and breast cancer risk: A case-control study nested in the Florence cohort of the EPIC (European Prospective Investigation into Cancer and nutrition) study.

Caini et al,

2023

Sci Total Environ

In a small case-control study of 150 women with breast cancer and age-matched controls, all of whom had never smoked, cobalt was inversely associated with breast cancer risk (OR=.33, 95%CI;0.12-.91). Other metals (cadmium, chromium, manganese, lead, and thallium) were not associated with breast cancer.

Human health risk assessment of arsenic, cadmium, lead, and mercury ingestion from baby foods

Parker, et al.

2022

Toxicol Rep

This study focused on arsenic (As) and lead (Pb) being in baby foods due to their known health risks, such as developmental, reproductive, and carcinogenic effects. Arsenic exposure comes mainly from rice-based products and could cause significant health risks. Lead was found in some grains and root vegetables, indicating potential exposure to health effects. The study concluded that exposure to these metals from baby foods had been found to be at safe levels. However, an exception was made for rice products because of arsenic natural abundance in soil. Even though levels of these metals in baby foods have been found to be under safe levels, monitoring of infant food should be continued for these metals and others.

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