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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.

Association between Urinary Phenols and Parabens as Well as Breast Cancer.

Wu et al,

2025

Iran J of Pub Health

This study of nearly 5,000 U.S. women found that exposure to triclosan—an antibacterial chemical once commonly found in soaps, toothpaste, and other personal care products—was associated with more than double the breast cancer risk at moderate exposure levels, while propylparaben (a preservative in cosmetics and foods) showed a protective association. However, when researchers examined the combined effect of multiple phenols and parabens together, they found no significant association with breast cancer, suggesting these chemicals may have complex and sometimes opposing effects. These mixed findings highlight the need for more research to understand how individual chemicals versus chemical mixtures affect breast cancer risk, especially since people are typically exposed to multiple chemicals simultaneously in everyday products.

Plasma perfluoroalkyl substances and breast cancer risk in Brazilian women: a case-control study.

Itoh et al,

2025

Environ Health

This case-control study of 942 Brazilian women (471 with breast cancer and 471 matched controls) found that higher blood levels of certain per- and polyfluoroalkyl substances (PFAS)—persistent environmental chemicals found in products like non-stick cookware and food packaging—were significantly associated with increased breast cancer risk. Specifically, elevated concentrations of n-perfluoroheptane sulfonate (n-PFHpS) doubled the breast cancer risk, and this association was particularly strong for hormone receptor-positive breast cancers and varied by ethnicity. The study emphasizes the importance of analyzing specific PFAS chemical variants (isomers) rather than treating all PFAS as identical, as different forms showed different associations with breast cancer risk across ethnic groups. These findings add to growing evidence that PFAS exposure may be a modifiable environmental risk factor for breast cancer, though the researchers note that previous studies have shown mixed results.

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.

Biological concentrations of DDT metabolites and breast cancer risk: an updated systematic review and meta-analysis.

Ugalde-Resano et al,

2025

Rev Environ Health

This comprehensive systematic review and meta-analysis examined the relationship between exposure to DDT (a banned pesticide that persists in the environment and human body) and breast cancer by analyzing studies published from 2000 to 2021. The analysis found positive associations between DDT exposure and breast cancer risk across multiple study types: in long-term prospective studies, women with higher p,p’-DDT levels had 41% increased odds of breast cancer, while retrospective studies showed 15% increased odds with p,p’-DDE exposure and 33% increased odds with high p,p’-DDT concentrations. The strongest association was observed with o,p’-DDT exposure, showing 2.24 times higher odds of breast cancer. These findings support a positive relationship between DDT exposure and breast cancer risk, reinforcing the importance of maintaining the worldwide ban on DDT use, as this pesticide remains in human bodies for decades and continues to spread geographically even where it’s no longer applied.

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.

Ambient polycyclic aromatic hydrocarbon exposure and breast cancer risk in a population-based Canadian case-control study.

Hinton et al,

2024

Cancer Causes Cont

This large Canadian population-based study examined whether long-term residential exposure to polycyclic aromatic hydrocarbons (PAHs)—widespread environmental pollutants from sources like vehicle exhaust and industrial emissions—increases breast cancer risk. Using 20 years of residential history data, researchers found that exposure to fluoranthene (a common PAH) was associated with significantly increased risk of premenopausal breast cancer, with women in moderately high exposure areas showing 59-148% higher risk compared to those in low-exposure areas. The associations with postmenopausal breast cancer were inconsistent, with only one analysis showing a modest increased risk. These findings support the hypothesis that ambient PAH exposure may increase the risk of breast cancer in premenopausal women, though the relationship appears complex and requires further investigation.

Carcinogenic industrial air pollution and postmenopausal breast cancer risk in the National Institutes of Health AARP Diet and Health Study.

Madrigal et al,

2024

Environ Int

This large prospective study of over 170,000 women in the NIH-AARP Diet and Health Study examined whether air emissions of 19 known or suspected carcinogenic chemicals from industrial facilities (1987-1995) were associated with postmenopausal breast cancer risk through 2018. Women living within 1 km of high benzene emissions had more than double the breast cancer risk compared to unexposed women (HR=2.06, 95% CI: 1.34-3.17, p-trend=0.001), with the association weakening at greater distances and appearing strongest for invasive rather than ductal carcinoma in situ. Elevated risk was also observed for vinyl chloride exposure at 5 km distance (HR=1.20, 95% CI: 1.01-1.43, p-trend=0.04), with suggestive but unclear associations for asbestos, trichloroethylene, and styrene. These findings indicate that residential proximity to industrial facilities emitting benzene and other carcinogens may increase breast cancer risk, warranting further investigation particularly in diverse populations living near high concentrations of industrial sources.

Exposure to di-2-ethylhexyl phthalate and breast neoplasm incidence: A cohort study.

Tang et al,

2024

Sci Total Environ

This large prospective cohort study investigated the association between DEHP exposure and breast neoplasms in 273,295 women from the UK Biobank, using modeled DEHP levels from environmental data and Cox regression analysis. Results showed that higher baseline and long-term DEHP exposure was positively associated with increased risk of malignant neoplasm, carcinoma in situ, and benign breast neoplasms, with suggestive higher risk in younger women and oral contraceptive users.

Risk of breast cancer in daughters of agricultural workers in Denmark.

Elbaek Pedersen et al,

2024

Environ Res

This large Danish study of over 5,500 breast cancer cases found that daughters whose mothers worked in horticulture (greenhouse and nursery work) before conception or during pregnancy had significantly increased breast cancer risk—79% higher for estrogen receptor-positive tumors and 148% higher for estrogen receptor-negative tumors. The associations were particularly strong for maternal horticulture work compared to paternal work, suggesting that pesticide and chemical exposures during critical windows of fetal development may affect daughters’ breast cancer risk decades later. These findings are concerning because horticultural workers have high exposure to pesticides and other agricultural chemicals, and the study suggests that even preconceptional maternal exposure—before pregnancy begins—may influence a daughter’s future cancer risk, highlighting the potential for intergenerational effects of occupational chemical exposures.

Blood Lead Level as Marker of Increased Risk of Ovarian Cancer in BRCA1 Carriers.

Kiljańczyk et al,

2024

Nutrients

This study of 989 women with BRCA1 mutations in Poland examined whether blood lead levels affect cancer risk in this high-risk population. Women with elevated blood lead levels (above 13.6 μg/L) showed 3.33 times higher risk of developing ovarian cancer (95% CI: 1.23-9.00, p=0.02) compared to those with lower levels, though this association lost significance after adjusting for other factors (HR=2.10, 95% CI: 0.73-6.01), while no significant association was found with breast cancer risk. These findings suggest that lead exposure may be an additional risk factor for ovarian cancer in BRCA1 mutation carriers and could inform the timing of preventive surgery (removal of ovaries and fallopian tubes) in this population. The authors recommend validation of these findings in other populations and investigation of whether reducing lead exposure through detoxification could lower ovarian cancer risk in BRCA1 carriers.

Mitochondrial DNA copy number mediated the associations between perfluoroalkyl substances and breast cancer incidence: A prospective case-cohort study.

Feng et al,

2024

Sci Total Environ

A Chinese study of 226 breast cancer cases and 990 controls found that exposure to certain perfluoroalkyl substances (PFAS), particularly perfluorononanoic acid (PFNA) and perfluoroheptanoic acid (PFHpA), was associated with increased mitochondrial DNA copy number (mtDNAcn) in blood, which in turn was linked to breast cancer risk. Women with the highest mtDNAcn levels had a 234% increased risk of breast cancer and a 271% increased risk of postmenopausal breast cancer compared to those with the lowest levels. The study found that mtDNAcn mediated about 15% of the relationship between PFHpA exposure and breast cancer, suggesting that PFAS may increase breast cancer risk partly by affecting mitochondrial function. These findings provide new insights into how PFAS chemicals may contribute to breast cancer development through effects on cellular energy production and mitochondrial health.

Perfluoroalkyl substances exposure and the risk of breast cancer: A nested case-control study in Jinchang Cohort.

Dou et al,

2024

Environ Res

A decade-long study of 135 breast cancer cases and 540 controls found that exposure to PFAS (perfluoroalkyl substances) was strongly associated with increased breast cancer risk, with mixed PFAS exposure showing more than double the odds of developing the disease. Several specific PFAS compounds—including PFBA, PFOS, PFHxS, and PFDA—were identified as particularly significant risk factors, with some associations appearing exclusively in premenopausal women. The findings suggest that premenopausal women should be especially cautious about PFAS exposure, as these persistent “forever chemicals” may pose a substantial breast cancer risk.

Exposure to per- and polyfluoroalkyl substances and breast cancer risk: a systematic review and meta-analysis of epidemiologic studies.

Chang et al,

2024

Am J Epidemiol

This systematic review of 18 epidemiological studies evaluated whether exposure to PFAS—measured in blood or plasma—is associated with breast cancer risk. Across 11 of the studies included in the meta-analysis, higher concentrations of common PFAS such as PFOA and PFOS were not associated with increased breast cancer risk (per-log-unit RR for PFOA = 0.95, 95% CI: 0.77–1.18; PFOS = 0.98, 95% CI: 0.87–1.11). When analyses were restricted to studies where PFAS levels were measured before diagnosis, risk estimates were slightly higher (for PFOA: RR = 1.16, 95% CI: 0.96–1.40), but still not statistically significant. Overall, the evidence suggests that current PFAS exposures measured do not show a consistent link to breast cancer, though the authors note substantial study variability and the need for better prospective data.

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.

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.

Systematic review and meta-analysis of breast cancer risks in relation to 2,3,7,8-tetrachlorodibenzo-p-dioxin and per- and polyfluoroalkyl substances.

Cong et al,

2023

Environ Sci Poll Res

This meta-analysis pooled data from 17 epidemiological studies to examine whether exposure to the dioxin compound 2,3,7,8-TCDD or to per- and polyfluoroalkyl substances (PFAS) is associated with breast cancer risk. The authors found evidence of a modest but statistically significant increased breast cancer risk associated with TCDD levels in the body,

Serum perfluorooctane sulfonate and perfluorooctanoate and risk of postmenopausal breast cancer according to hormone receptor status: An analysis in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

Chang et al,

2023

Int J Cancer

This study of over 1,200 postmenopausal women found that higher blood levels of PFOS (a common “forever chemical” found in items like stain-resistant fabrics and food packaging) were associated with 59-134% increased risk of hormone receptor-positive breast cancers, while PFOA (another widespread PFAS chemical) showed modest associations with hormone receptor-negative tumors. PFAS are called “forever chemicals” because they persist indefinitely in the environment and human body, and these findings suggest they may contribute to breast cancer through hormone disruption. These results add to growing concerns about PFAS exposure from contaminated water, food packaging, and consumer products, though the different associations for PFOS and PFOA by tumor subtype require further investigation to fully understand how these chemicals affect breast cancer development.

Combined and progestagen-only hormonal contraceptives and breast cancer risk: A UK nested case-control study and meta-analysis.

Fitzpatrick et al,

2023

PLOS Med

A large UK study of nearly 10,000 breast cancer cases found that current or recent use of progestagen-only contraceptives (including pills, injections, implants, and IUDs) was associated with a 21-32% increased breast cancer risk, similar to the risk from combined oral contraceptives containing both estrogen and progestagen. The absolute risk increase is small and age-dependent: for women using hormonal contraceptives for 5 years, the excess risk translates to 8 additional breast cancer cases per 100,000 users among women aged 16-20, but rises to 265 additional cases per 100,000 users among women aged 35-39. While these findings add important evidence about hormonal contraceptive risks, the small increased risk must be weighed against the significant benefits of contraception during childbearing years, and women should discuss their individual risk-benefit profile with their healthcare providers when choosing contraceptive methods.

Urinary concentration of endocrine-disrupting phthalates and breast cancer risk in Indian women: A case-control study with a focus on mutations in phthalate-responsive genes.

Mukherjee Das et al,

2022

Cancer Epiemiol

The first Indian case-control study examining phthalates (chemicals widely used in plastics, cosmetics, and food packaging) and breast cancer found that women with higher urinary levels of di-butyl phthalate (DBP) had 1.5 times increased breast cancer risk, while those with higher DEHP levels had nearly 3 times increased risk. Analysis of breast tumor tissue revealed mutations in several genes known to respond to phthalate exposure, affecting pathways involved in hormones, metabolism, and cancer development. These findings suggest that exposure to certain phthalates may increase breast cancer risk through genetic changes, though larger studies are needed to confirm these results and understand how early-life exposures might contribute to cancer development later in life.

Elevated levels of perfluoroalkyl substances in breast cancer patients within the Greater Manila Area.

Velarde et al,

2022

Chemosphere

Researchers measured 41 endocrine-disrupting chemicals (EDCs) in women living in the Greater Manila Area, Philippines, comparing those with and without breast cancer. They found that certain perfluoroalkyl substances (PFAS) were significantly associated with breast cancer, with some chemicals showing dramatically increased risk: PFDoA was associated with a 1,263% increased risk, PFDA with an 826% increased risk, and PFHxA with a 166% increased risk. Long-chain PFAS levels were higher in women from heavily industrialized areas compared to the National Capital Region. This study provides the first baseline data on EDC exposure levels in Filipino women, filling a critical gap in knowledge about chemical exposures in Southeast Asian populations and suggesting that industrial pollution may be contributing to elevated PFAS levels and breast cancer risk.

Urinary bisphenol A and its interaction with CYP17A1 rs743572 are associated with breast cancer risk.

He et al,

2022

Chemosphere

This case-control study found that higher urinary bisphenol A (BPA) levels were significantly associated with increased breast cancer (BC) risk, with a 54% higher risk per 1-unit increase in log-transformed BPA (95% CI: 1.34–1.77, P < 0.001). Additionally, genetic variation in the CYP17A1 gene (rs743572) significantly modified this association, with individuals carrying both high BPA levels and the GA+AA genotype showing a 2.49-fold increased BC risk (P interaction = 0.020).

Positive association between dietary exposure to polybrominated diphenyl ethers and breast cancer risk in the French E3N cohort: The role of vegetable oil consumption.

Frenoy et al,

2022

Environ Int

A large French study of nearly 68,000 women followed for over 21 years found that dietary exposure to PBDEs (flame retardant chemicals) was associated with increased breast cancer risk, but importantly, this association was modified by vegetable oil consumption. Women who consumed higher amounts of vegetable oil (≥4.6 g/day) and had the highest PBDE intake showed a 23% increased breast cancer risk, while those with low vegetable oil consumption showed no increased risk regardless of PBDE exposure. These findings suggest that the interaction between diet and chemical contaminants is important to consider when developing public health recommendations, as certain dietary patterns may amplify or mitigate the health risks associated with environmental chemical exposures.

Perfluoroalkyl substances (PFASs) as risk factors for breast cancer: a case-control study in Chinese population.

Li et al,

2022

Environ Health

This large Chinese case-control study of 373 breast cancer patients and 657 controls found that higher plasma levels of PFOA and PFDA were positively associated with breast cancer risk, with PFOA showing particularly strong associations with hormone receptor-positive and HER2-positive breast cancers (47%, 36%, and 62% increased odds, respectively). Interestingly, the study found that PFTrDA (a longer-chain PFAS) was inversely associated with breast cancer risk, though the reasons for this protective effect are unclear. The findings add to growing international evidence linking PFAS exposure to breast cancer, demonstrating that these “forever chemicals” pose breast cancer risks not just in Europe and America but also in Asian populations. These results are concerning because PFOS was found at the highest concentrations in blood samples from both cases and controls, indicating widespread population exposure to these persistent environmental contaminants in Chin

Oral Contraceptive Use and Breast Cancer Risk for BRCA1 and BRCA2 Mutation Carriers: Systematic Review and Meta-Analysis of Case-Control Studies.

Barańska et al,

2022

Cancers

This meta-analysis of nine studies involving over 33,000 women with BRCA1 or BRCA2 gene mutations. One significant finding was that women who first started using oral contraceptives at age 20 or older had a 21% increased risk of breast cancer compared to those who never used them. These findings suggest that the timing of oral contraceptive use may be important for women with BRCA mutations, though more research is needed to fully understand the relationship between hormonal contraception and cancer risk in genetic mutation carriers.

Plasma perfluoroalkyl substance exposure and incidence risk of breast cancer: A case-cohort study in the Dongfeng-Tongji cohort.

Feng et al,

2022

Environ Pollut

This Chinese prospective study of over 1,200 women found that higher baseline plasma concentrations of PFOA and PFHpA (a shorter-chain PFAS) were associated with 35% and 20% increased risk of developing breast cancer, respectively, with similar or stronger associations seen in postmenopausal women. When researchers examined the combined effect of all perfluorinated carboxylic acids together, they found a 19% increased breast cancer risk for each quartile increase in exposure, with PFOA accounting for more than half of this effect. Importantly, this is the first study to identify PFHpA—a shorter-chain PFAS increasingly used as a replacement for longer-chain compounds—as a breast cancer risk factor, raising concerns that newer “replacement” PFAS chemicals may not be safer alternatives. These prospective findings strengthen the evidence that PFAS exposure is a modifiable risk factor for breast cancer and support the need to regulate PFAS as an entire chemical class rather than individual compounds.

Associations between Polyfluoroalkyl Substances Exposure and Breast Cancer: A Meta-Analysis.

Jiang et al,

2022

Toxics

A meta-analysis of eight studies examining the relationship between PFAS chemicals and breast cancer found that two specific PFAS compounds—PFOA and PFHxS—were associated with significantly increased breast cancer risk, showing 32% and 79% elevated risk respectively. Surprisingly, PFNA showed a protective association with 24% reduced risk, while PFOS showed no association with breast cancer risk, though all findings had substantial statistical heterogeneity between studies. The researchers concluded that certain PFAS compounds may be potential breast cancer risk factors, with concerning evidence that even low-level exposures could have harmful impacts on human health, highlighting the need for further research to clarify the varied effects of different PFAS chemicals on breast cancer development.

Risk of breast cancer associated with long-term exposure to benzo[a]pyrene (BaP) air pollution: Evidence from the French E3N cohort study.

Amadou et al,

2021

Environ Int

Long-term exposure to benzo[a]pyrene (BaP), a toxic air pollutant from gas and diesel vehicle exhaust, was associated with a 15% increased risk of breast cancer in a large French study of over 10,000 women. The risk was particularly elevated in women transitioning through menopause and for hormone receptor-positive breast cancers, with each increase in BaP exposure levels raising breast cancer odds by 15-20%. This study provides important real-world evidence that BaP air pollution may contribute to breast cancer development, especially affecting hormone-sensitive tumors.

Exposure to bisphenol A and breast cancer risk in northern Mexican women.

López-Carrillo et al,

2021

Int Arch Occup Environ Health

This case–control study in Northern Mexican women (394 breast cancer cases, 404 matched controls) measured urinary free-BPA (BPA‑F) and found that the highest exposure group had a statistically significant 2.31‑fold increased odds of breast cancer (95% CI: 1.43–3.74) compared to the lowest group. The authors concluded that BPA‑F may act as an environmental cofactor in breast carcinogenesis, although findings need replication.

Exposure to light at night (LAN) and risk of breast cancer: A systematic review and meta-analysis.

Lai et al,

2021

Sci Total Environ

This meta-analysis combined data from multiple studies to examine whether exposure to artificial light at night (LAN) — both outdoor and indoor — is associated with breast cancer risk. Women in the highest exposure categories had about a 12% greater risk of developing breast cancer compared with those in the lowest exposure categories (summary relative risk = 1.12, 95% CI: 1.06–1.18 for outdoor LAN; 1.13, 95% CI: 1.05–1.21 for indoor LAN). The association was somewhat stronger for estrogen-receptor–positive tumors. The authors concluded that LAN is a plausible, albeit modest, environmental risk factor for breast cancer.

Exposure to outdoor light at night and risk of breast cancer: A systematic review and meta-analysis of observational studies.

Wu et al,

2021

Environ Pollut

This meta-analysis synthesized data from 6 observational studies that used satellite-based measures of outdoor “light at night” (LAN) exposure to assess associations with breast cancer risk. Women in the highest-exposure group had were more likely to be diagnosed with breast cancer compared than those in the lowest-exposure group (OR = 1.11, 95% CI: 1.06–1.16). In subgroup analyses, the association remained significant for postmenopausal women (OR ≈ 1.07, 95% CI: 1.00–1.13).

Serum perfluoroalkyl substances and breast cancer risk in Japanese women: A case-control study.

Itoh et al,

2021

Sci Total Environ

This Japanese case-control study of 405 matched pairs of women found that higher serum concentrations of PFAS chemicals were generally associated with reduced breast cancer risk rather than increased risk, with women in the highest exposure quartile showing 79-85% lower odds of breast cancer for linear isomers of PFOS and PFOA. However, the study revealed important differences between chemical structures: among postmenopausal women, while the linear form of one PFAS (PFTrDA) was protective, the branched form showed a marginally increased risk (74% higher odds approaching significance at medium exposure levels). These unexpected inverse associations contrast with several other studies showing increased breast cancer risk from PFAS exposure, highlighting the complexity of PFAS research and the importance of distinguishing between different chemical structures (branched vs. linear isomers) that may have opposite health effects, though the reasons for these protective associations remain unclear and warrant further investigation.

A case-control study of perfluoroalkyl substances and the risk of breast cancer in Taiwanese women.

Tsai et al,

2020

Environ Int

This Taiwanese study of 239 women found that higher plasma levels of PFOS (a “forever chemical”) were associated with 134% increased breast cancer risk in women aged 50 and younger, with each natural log unit increase in exposure more than doubling the odds of developing the disease. Both PFOS and PFHxS (another PFAS chemical) showed positive associations specifically with estrogen receptor-positive breast tumors in younger women, suggesting these endocrine-disrupting chemicals may particularly affect hormone-sensitive breast cancers during reproductive years. These findings are concerning because PFAS are ubiquitous environmental contaminants found in water, food packaging, and consumer products, and the study adds to growing evidence that these persistent chemicals may contribute to rising breast cancer rates among younger women. The results highlight the potential health consequences of widespread PFAS contamination, particularly for women of reproductive age who may face elevated risk of hormone-driven breast cancers.

Perfluorinated alkylated substances serum concentration and breast cancer risk: Evidence from a nested case-control study in the French E3N cohort.

Mancini et al,

2020

Int J Cancer

his French study of 388 women found that higher blood levels of PFOS (a “forever chemical”) were associated with 122-133% increased breast cancer risk for estrogen receptor-positive tumors and 147-176% increased risk for progesterone receptor-positive tumors, with a clear dose-response relationship showing increasing risk at higher exposure levels. Interestingly, the study found different patterns for hormone receptor-negative tumors, where only low-to-moderate levels of PFOS and PFOA were associated with dramatically increased risk (up to 1,440% for estrogen receptor-negative tumors at moderate PFOS levels). These findings suggest that PFAS chemicals—which are widespread in human blood worldwide due to contamination from products like stain-resistant fabrics, non-stick cookware, and food packaging—may contribute to breast cancer through different mechanisms depending on tumor type, highlighting the complexity of how these persistent environmental chemicals affect breast cancer risk.

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.

Exposure to organophosphorus insecticides and increased risks of health and cancer in US women.

Sun et al,

2020

Environ Toxicol Pharmacol

This analysis of US health data from 2003-2012 found that women with higher long-term exposure to organophosphorus insecticides (common pesticides measured through urine samples) faced significantly elevated health risks, including three times higher risk of cardiovascular disease and 2.7 times higher overall cancer risk among women aged 60-85. Women with higher pesticide exposure also showed increased risks of asthma in younger age groups and chronic bronchitis in older age, with breast cancer risk elevated among female smokers and prostate cancer risk elevated among male smokers. These findings suggest that chronic exposure to these widely-used agricultural pesticides may pose greater health threats to women than men, particularly for cardiovascular disease and cancer.

Association of Menopausal Hormone Therapy With Breast Cancer Incidence and Mortality During Long-term Follow-up of the Women’s Health Initiative Randomized Clinical Trials.

Chlebowski et al,

2020

JAMA

This long-term follow-up study of over 27,000 postmenopausal women in the Women’s Health Initiative tracked breast cancer outcomes for more than 20 years after participants were randomized to receive either hormone therapy or placebo. The results showed strikingly different effects depending on the type of hormone therapy: estrogen alone (CEE) in women who had undergone hysterectomy was associated with 22% lower breast cancer incidence and 40% lower breast cancer mortality, while estrogen plus progestin (CEE plus MPA) in women with an intact uterus was associated with 28% higher breast cancer incidence but no significant difference in breast cancer mortality. These findings indicate that the addition of progestin to estrogen therapy substantially changes its impact on breast cancer risk, with estrogen-alone therapy appearing protective and estrogen-plus-progestin therapy increasing risk. The study helps resolve longstanding uncertainty about menopausal hormone therapy and breast cancer by demonstrating that the type of hormone therapy and whether a woman has had a hysterectomy are critical factors in determining breast cancer outcomes.

Use of hormone replacement therapy and risk of breast cancer: nested case-control studies using the QResearch and CPRD databases.

Vinogradova et al,

2020

Br Med J

A large UK study of 98,611 women with breast cancer and 457,498 controls found that long-term hormone replacement therapy (HRT) use (≥5 years) was associated with significantly increased breast cancer risk, with combined estrogen-progestogen therapy showing a 79% increased risk and estrogen-only therapy showing a 15% increased risk. Among combined therapies, norethisterone carried the highest risk (88% increase) while dydrogesterone showed the lowest (24% increase), and importantly, the increased risk from past long-term combined therapy use persisted even after stopping treatment (16% increased risk). In practical terms, recent combined HRT users could expect 9-36 extra breast cancer cases per 10,000 women per year depending on age, while estrogen-only users would see 3-8 extra cases per 10,000 women per year, providing critical information for women and clinicians weighing the benefits and risks of different HRT regimens.

DDT and Breast Cancer: Prospective Study of Induction Time and Susceptibility Windows.

Cohn et al,

2019

J Natl Cancer Inst

This study of over 700 women found that DDT exposure was associated with increased breast cancer risk through age 54, but the timing of first exposure mattered critically: women first exposed to DDT after infancy had nearly triple the risk of early postmenopausal breast cancer (ages 50-54), while women first exposed during infancy through puberty had nearly four times the risk of premenopausal breast cancer (before age 50). These findings suggest there are specific windows of vulnerability when DDT exposure has the strongest impact on future breast cancer risk, with effects that can persist for decades. The results support the idea that DDT acts as an endocrine disruptor affecting breast tissue throughout a woman’s life—from before birth through menopause—even though DDT was banned in the U.S. in 1972, highlighting the long-term health consequences of early-life chemical exposures.

Alkylphenolic compounds and risk of breast and prostate cancer in the MCC-Spain study.

Peremiquel-Trillas et al,

2019

Environ Int

This population-based case-control study investigated whether occupational exposure to alkylphenolic compounds—endocrine-disrupting chemicals widely used in industry—is associated with breast and prostate cancer. The study included over 5,600 participants and found that occupational exposure to alkylphenolic compounds was modestly associated with increased breast cancer risk (23% increase), particularly from exposure to domestic cleaning products and nonylphenol ethoxylates. No significant associations were found between alkylphenolic compound exposure and prostate cancer overall, except among men exposed through cosmetics and personal hygiene products. The authors conclude these findings suggest a modest link between occupational alkylphenolic compound exposure and breast cancer that requires further confirmation in additional studies.

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.

Environmental Exposure to Pesticides and Breast Cancer in a Region of Intensive Agribusiness Activity in Brazil: A Case-Control Study.

Silva et al,

2019

Int J Env Res Pub Health

This Brazilian case-control study of 351 women in an intensive agricultural region found that women living near cropland where pesticides are used had more than twice the risk of developing breast cancer compared to those who didn’t live near such areas. The study also found that women over 50 who experienced early menarche (first menstrual period at 9-12 years) had approximately double the breast cancer risk. These findings suggest that residential proximity to pesticide-treated agricultural land may be an important environmental risk factor for breast cancer, adding to concerns about pesticide exposure beyond just occupational settings or dietary intake.

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.

Phthalate Exposure and Breast Cancer Incidence: A Danish Nationwide Cohort Study.

Ahern et al,

2019

J Clin Oncl

This large-scale Danish nationwide study followed 1.12 million women over nearly 10 million woman-years to examine the relationship between phthalate exposure from prescription medications and breast cancer risk. The researchers tracked phthalate exposure by linking a database of drug ingredients with prescription records, finding that most phthalate exposures were not associated with increased breast cancer risk. However, high-level cumulative exposure to dibutyl phthalate (≥10,000 mg) was associated with approximately double the risk of estrogen receptor-positive breast cancer, consistent with laboratory evidence showing this compound has estrogenic effects. The study concludes that women should avoid high-level dibutyl phthalate exposure, particularly through long-term use of pharmaceuticals containing this compound, though lower exposure levels did not increase breast cancer risk.

Plasma levels of dichlorodiphenyldichloroethene (DDE) and dichlorodiphenyltrichloroethane (DDT) and survival following breast cancer in the Carolina Breast Cancer Study.

Parada et al,

2019

Environ Int

This 20-year study of 748 women diagnosed with breast cancer in North Carolina found that those with the highest levels of DDE (a breakdown product of the banned pesticide DDT) in their blood had nearly twice the risk of death compared to those with the lowest levels. The association between DDE exposure and breast cancer death was particularly strong among Black women and women with estrogen receptor-negative tumors, with Black women showing more than double the mortality risk. Since DDT was banned in the U.S. in 1972 but DDE persists in the environment and body fat for decades, these findings suggest that legacy pesticide exposure may contribute to worse breast cancer outcomes and racial disparities in breast cancer survival.

Prepubertal and Pubertal Endocrine-Disrupting Chemical Exposure and Breast Density among Chilean Adolescents.

Binder et al,

2018

Cancer Epidemiol Biomarkers Prev

This study examined how exposure to endocrine-disrupting chemicals (EDCs) during puberty affects breast tissue development in 200 Chilean girls by measuring urinary concentrations of phenols and phthalates at two stages of breast development and assessing breast density. The researchers found that certain phthalate metabolites were associated with increased breast density measures – specifically, higher levels of monocarboxyisooctyl phthalate were linked to 7% higher percent dense breast tissue, and monoethyl phthalate was associated with increased fibroglandular volume. Bisphenol A showed a U-shaped relationship with fibroglandular volume, where girls with middle-level exposures had at least 10% lower fibroglandular volume compared to those with low or high exposures. The findings suggest that developing breast tissue is vulnerable to certain EDCs during childhood and adolescence, which may have implications for future breast cancer risk since breast density is a known risk factor.

Night shift work and breast cancer: a pooled analysis of population-based case-control studies with complete work history.

Cordina-Duverger et al,

2018

Eur J Epidemiol

This large international study pooling data from over 13,000 women across five countries found that night shift work increased breast cancer risk by 26% in pre-menopausal women, with the risk rising substantially for those working longer shifts (≥10 hours), more frequent nights (≥3 nights per week), or longer durations (≥10 years). Pre-menopausal women working both long durations and high frequency had a 2.5 times higher breast cancer risk, with current or recent night workers at higher risk than those who had stopped more than two years ago. Notably, no increased risk was found in post-menopausal women, and the elevated risk was primarily for estrogen receptor-positive tumors, particularly those that were also HER2-positive, suggesting that disruption of hormones and circadian rhythms during reproductive years may be key factors in how night work affects breast cancer risk.

Urban Neighborhood and Residential Factors Associated with Breast Cancer in African American Women: a Systematic Review.

Smith et al,

2018

Discov Oncol

This systematic review examined the relation of 4 neighborhood factors on breast cancer incidence and prognosis among African-American women: neighborhood socioeconomic status (nSES), residential segregation, spatial access to mammography, and residential pollution. The authors found that nSES, residential segregation and access to mammography were all related to stage at diagnosis, and nSES and living in more segregated areas were both associated with mortality. Residential pollution was not associated with increased risk of breast cancer in the studies reviewed.

Evaluation of estrogenic and anti-estrogenic activity of endocrine disruptors using breast cancer spheroids: a comparative study of T47D and MCF7 cell lines in 2D and 3D models

Barbaro et al,

2025

Front Toxicol

The study examined the estrogenic and anti-estrogenic effects of three endocrine disruptors: Bisphenol A (BPA), which mimics estrogen, 17 -Estradiol (E2), the endogenous nuclear estrogen receptor ligand, and Fulvestrant (FUL), a drug that interferes with proper estrogen function. The experiment measured the influence of the endocrine disruptors in vitro using 2D and 3D T47D and MCF7 cells, which are estrogen receptor-positive human breast cancer cells. The study results concluded that E2 and BPA increased the expression of the estrogen-regulated marker pS2 and decreased TGF 3. Meanwhile, FUL inhibited E2 and BPA’s expression of the estrogen-regulated markers, meaning FUL reversed the effects of the other two endocrine disruptors.

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.

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