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2022
Biomed Pharmacother
A review of endocrine-disrupting chemicals (EDCs)—ubiquitous substances found in cosmetics, plastic food packaging, and medicines that enter the body through skin, digestive, or respiratory routes—examined their toxic effects even at microgram doses on the female reproductive system and genetic mechanisms. EDCs disrupt endocrine functions by binding to steroid hormone receptors, interfering with hormone synthesis and secretion, and modulating epigenetic processes that can lead to gene expression disturbances, contributing to neoplastic diseases, neurological disorders, circulatory problems, and reproductive dysfunction. Prenatal exposure can affect offspring development, with particular impacts on ovarian function leading to reduced fertility through disturbances in steroid receptor function, steroidogenesis, and gametogenesis. The review emphasizes that despite widespread exposure to these chemicals in everyday products, continued research is needed to fully understand their effects on the female reproductive system and potential transgenerational impacts mediated through epigenetic mechanisms.
2022
Molecules
A review of endocrine-disrupting compounds (EDCs) in drinking water examines this emerging class of environmental contaminants—ranging from naturally occurring to synthetic compounds—that exist as complex mixtures at trace levels but can cause adverse health effects even at low concentrations. The review covers the perceived and actual health risks of EDC exposure through water ingestion (a major human exposure route), regulatory efforts to limit contamination, and analytical methods including advanced sample preparation, instrumentation, and bioassays for multiclass EDC identification and quantitation. Given that human exposure to EDCs via drinking water poses significant health concerns even at trace concentrations, the ability to detect and evaluate EDC contamination with high sensitivity and accuracy is critically important for protecting public health and informing regulatory policy.
2022
Ecotoxicology
An experimental study using wild-type and thyroid hormone receptor alpha knockout (thrαa⁻/⁻) zebrafish embryos/larvae found that avobenzone and octinoxate—organic UV filters commonly used in sunscreens and widely detected in water—disrupt the thyroid endocrine system, with significantly lower survival rates in thrαa⁻/⁻ fish exposed to ≥3 μM of either compound, indicating the thyroid hormone receptor plays a crucial role in their toxicity. Avobenzone exposure increased the T3:T4 ratio with upregulation of the deio2 gene, while both chemicals decreased T4 levels and triggered compensatory upregulation of hypothalamus and pituitary genes (trh, tshβ, tshr), indicating feedback mechanisms attempting to maintain hormonal homeostasis. These findings demonstrate that two widely used sunscreen ingredients act as thyroid endocrine disruptors by affecting thyroid hormone receptors and disrupting the hypothalamus-pituitary-thyroid (HPT) axis, raising concerns about aquatic environmental contamination from these chemicals and potential impacts on thyroid function in exposed organisms, including implications for human exposure through water and dermal application.
2022
Int J Environ Res Public Health
A recent study highlights the risk of Bisphenol A (BPA) exposure from bottled water, emphasizing how temperature can influence BPA leaching into the water. While BPA isn’t used in PET bottle manufacturing, contamination can occur due to recycled materials. Findings indicate that BPA levels in bottled water increase with temperature, even when not at the highest temperatures. BPA, a known endocrine-disrupting chemical (EDC), is linked to reproductive health issues, developmental disorders, and even cancer.
2022
Chin J Ind Hyg Occup Dis
A case-control study in Beijing examined 973 women (495 breast cancer patients and 478 controls) to identify occupational risk factors for breast cancer. The research found that women with a history of night shift work had a 70% increased risk of breast cancer, while those who worked mostly standing had double the risk compared to those who sat or alternated positions. The study concludes that night shift work and prolonged standing at work are significant occupational risk factors for female breast cancer. Establishing regular sleep schedules and avoiding extended periods of standing may help prevent breast cancer among working women.
2022
Cancer Epidemiol
A case-control study of 508 breast cancer cases and 892 controls from the Nigerian Integrative Epidemiology of Breast Cancer (NIBBLE) Study examined associations between leisure-time physical activity (LTPA) and breast cancer risk by molecular subtype, with immunohistochemical analysis available for 294 cases (43.2% hormone receptor-positive [HRP], 41.8% triple-negative [TNBC]). Women in the highest LTPA quartile (≥14.75 METs/hour/week) compared to the lowest (<3.75) had 49% lower odds of breast cancer overall (OR=0.51; 95% CI: 0.35-0.74) and 49% lower odds of TNBC (OR=0.51; 95% CI: 0.27-0.96) after adjusting for age, reproductive factors, body size, and other confounders, though the association with HRP breast cancer was not statistically significant (OR=0.61; 95% CI: 0.34-1.09), with stronger protective effects observed in women with BMI<30 versus BMI≥30. These findings suggest that leisure-time physical activity may reduce breast cancer risk in Sub-Saharan African women, particularly for triple-negative breast cancer—the more aggressive and prevalent molecular subtype in this population—highlighting physical activity as a potentially important modifiable risk factor for breast cancer prevention in African populations where TNBC rates are disproportionately high.
2022
Int J Cancer
A comprehensive two-sample Mendelian randomization study using Breast Cancer Association Consortium data examined potential causal associations of 23 risk factors and biomarkers with breast cancer risk overall and by molecular subtypes, identifying significant associations for 15 traits including reproductive factors (age at menarche/menopause), anthropometric measures (BMI, waist-to-hip ratio, height), lifestyle factors (physical activity, smoking, sleep duration, chronotype), and six blood biomarkers (estrogens, IGF-1, SHBG, telomere length, HDL-cholesterol, fasting insulin). Notably, the study revealed heterogeneous subtype-specific associations: increased SHBG reduced ER+ breast cancer risk (OR=0.83; 95% CI: 0.73-0.94) but elevated risk for ER- (OR=1.12) and triple-negative cancers (OR=1.19, p-heterogeneity=0.01), while higher fasting insulin increased HER2-negative cancer risk (OR=1.94; 95% CI: 1.18-3.20) but reduced HER2-enriched cancer risk (OR=0.46; 95% CI: 0.26-0.81, p-heterogeneity=0.006). These findings—consistent across sensitivity analyses—provide strong genetic evidence for causal relationships between multiple modifiable and biological risk factors and breast cancer, while revealing that SHBG and insulin have paradoxical opposite effects on different molecular subtypes, suggesting distinct etiologic pathways for ER+/ER- and HER2+/HER2- breast cancers that may require subtype-specific prevention strategies.
2022
Int J Epidemiol
A prospective cohort study of 45,923 never-smoking Norwegian women aged 34-70 followed for a mean 19.8 years (2,185 invasive breast cancer cases) found that exposure to second-hand smoke (SHS) from parents during childhood was associated with an 11% increased breast cancer risk (HR=1.11; 95% CI: 1.02-1.22) compared to unexposed women, with no difference by estrogen (p-heterogeneity=0.31) or progesterone (p-heterogeneity=0.95) receptor status. Among exposed women, the attributable fraction was 10.3% (95% CI: 1.8-18.0), indicating that approximately 1 in 10 breast cancer cases among those exposed could be attributed to parental SHS during childhood. These findings provide evidence that childhood exposure to parental second-hand smoke increases breast cancer risk decades later, highlighting childhood as a critical window of susceptibility to environmental tobacco smoke carcinogenesis and suggesting that the cancer burden attributable to SHS may be substantially underestimated when focusing only on adult exposures rather than early-life exposures.
2022
Cancer Epidemiol Biomark Prev
A study of 1,268 women from the Long Island Breast Cancer Study Project with measurements of 22 urinary phthalate and phenol analytes and leukocyte telomere length (LTL)—a biomarker of biological aging—found that LTL significantly modified associations between 11 of 22 analytes and breast cancer risk (p<0.05), with a general pattern showing inverse associations at shorter LTL and positive associations at longer LTL, though no modifying effects were observed for breast cancer mortality. This first study examining biological aging's role in environmental chemical-breast cancer associations reveals complex interactions where the same phthalate/phenol exposures may have opposite effects depending on an individual's telomere length and biological aging status. These findings suggest that biological aging markers like telomere length may help identify women who are more or less susceptible to breast cancer from environmental chemical exposures, highlighting the importance of considering individual variation in biological aging when assessing environmental risk factors and potentially explaining some of the inconsistent associations between phthalates/phenols and breast cancer reported in previous studies that did not account for biological aging heterogeneity.
2022
Cancer Epidemiol
A hospital-based case-control study of 379 histologically confirmed breast cancer cases and 403 controls in Lagos and Abuja, Nigeria (October 2016-May 2017) examined associations between physical activity and breast cancer risk using metabolic equivalent (MET) hours per week across occupational, household, transport, and leisure domains. Women in the upper-middle category of total physical activity had 56% reduced breast cancer risk (AOR=0.44; 95% CI: 0.27-0.78), with particularly strong protective effects for total non-vigorous PA (AOR=0.26; 95% CI: 0.09-0.75), household PA (AOR=0.38; 95% CI: 0.20-0.71), and occupational PA (AOR=0.64; 95% CI: 0.40-1.02), while transport and leisure PA showed no significant associations. These findings—among the first examining physical activity and breast cancer in sub-Saharan Africa—suggest that the cumulative effect of various daily physical activities, particularly household and occupational activities common among Nigerian women, substantially reduces breast cancer risk and should be promoted as part of breast cancer prevention strategies in Nigeria and potentially other low- and middle-income countries where physical activity patterns differ from high-income countries with predominantly leisure-time activity.
2021
Endocrinology
A comprehensive review of bisphenol A (BPA) research spanning over 20 years—from the landmark 1997 study showing reproductive effects in male mouse offspring at 2 µg/kg/day through the CLARITY-BPA study designed to bridge regulatory and scientific disagreements—found that thousands of animal studies and over 100 epidemiological studies report adverse effects at low doses, with CLARITY-BPA showing effects at 2.5 µg/kg/day, leading independent experts to recommend dropping the lowest observed adverse effect level 20,000-fold from 50,000 to 2.5 µg/kg/day. Despite this overwhelming evidence, the FDA continues to assert BPA is safe by rejecting low-dose data as “not biologically plausible” based on four incorrect assumptions criticized by the Endocrine Society as violating basic principles of endocrinology: that dose responses must be monotonic, thresholds exist below which there are no effects, both sexes must respond similarly, and only traditional toxicological guideline studies are valid. The review highlights a fundamental divide between regulatory approaches and endocrine science, demonstrating that traditional toxicology methods are insufficient for evaluating endocrine-disrupting chemicals like BPA, which can cause non-monotonic dose responses, sex-specific effects, and low-dose effects that challenge conventional assumptions about chemical safety, yet regulatory agencies continue to ignore modern endocrinology principles in favor of outdated toxicological paradigms.
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.
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.
2021
Int J Health Geogr
A systematic review and dose-response meta-analysis of 17 studies found that exposure to light at night (LAN)—both outdoor and indoor—was associated with an 11% increased breast cancer risk overall, with slightly stronger associations in premenopausal women (16% increased risk) and ER-positive breast cancers (9% increased risk). The dose-response analysis of outdoor LAN showed a linear relationship up to 40 nW/cm²/sr, after which the curve flattened, particularly among premenopausal women, suggesting a threshold effect. These findings provide the first comprehensive dose-response assessment of the LAN-breast cancer relationship and support growing concerns about light pollution as an environmental breast cancer risk factor, with implications for urban planning, building design, and personal light exposure habits—particularly for younger women who appear most vulnerable to the carcinogenic effects of circadian disruption from artificial light exposure at night.
2021
BMC Women's Health
A meta-analysis of 26 studies including over 1.3 million participants found that short-term night-shift work (<10 years) was associated with a 13% increased breast cancer risk, but surprisingly, long-term night-shift work (≥10 years) showed no statistically significant increased risk (8% increase, not significant). Flight attendants with long overnight flights showed elevated breast cancer risk, though unmeasured confounders may have influenced these results, and the increased risk in short-term workers was most robust in case-control studies that adjusted for reproductive factors and family history. The paradoxical finding that short-term but not long-term night-shift work showed significant associations contradicts the expected dose-response relationship and may reflect healthy worker bias (where women susceptible to night-shift effects leave such work before reaching 10 years), methodological limitations in measuring long-term exposures, or unmeasured confounding factors that accumulate differently over time.
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.
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.
2021
Water Res
A study of 101 bottled water products sold in the US found that PFAS chemicals were detected in 39% of tested products at concentrations ranging from 0.17 to 18.87 ng/L (median 0.98 ng/L), with 97% of samples below 5 ng/L, though some products approached levels of regulatory concern. Spring water products contained significantly higher PFAS levels than purified water, with reverse osmosis (RO) treatment—used in 71% of purified waters but only 2% of spring waters—effectively removing PFAS contamination across all chain lengths. Notably, perfluoropropanoic acid (PFPrA), an ultrashort-chain PFAS measured for the first time in bottled water, accounted for 42% of detected PFAS mass and was found almost exclusively in spring water products, raising concerns given the lack of enforceable PFAS regulations for bottled water in the US despite these “forever chemicals” being linked to multiple health concerns including potential breast cancer risk, and highlighting the need for mandatory PFAS monitoring and disclosure requirements for bottled water manufacturers.
2021
Environ Res
Biodegradable polymers are emerging as a promising solution for removing endocrine-disrupting chemicals (EDCs) from wastewater. EDC’s, found in pharmaceuticals, pesticides, and personal care products pose serious health risks, impacting the endocrine system and disrupting reproductive health. Traditional water treatments often fail to fully remove EDCs. Biodegradable polymers, with strong adsorptive properties, offer a sustainable and effective method, helping to minimize EDC exposure and protect human and environmental health.
2021
Adv Pharmacol
A comprehensive review examining endocrine-disrupting chemicals (EDCs) in breast tissue concludes that hundreds of these environmental chemicals are entering human breast tissue and contributing to the global rise in breast cancer incidence through multiple biological mechanisms. Laboratory studies demonstrate that EDCs can activate all the established “hallmarks of cancer” in human breast cancer cells—even at concentrations measured in actual human breast tissue—with effects amplified when chemicals are present as mixtures rather than individually. The authors argue that EDCs must now be formally recognized as a breast cancer risk factor to enable prevention strategies that include reducing environmental chemical exposures, particularly given that the varied mixtures of EDCs found in individual breast tissues act through overlapping mechanisms to promote cancer development.
2021
Sci Rep
A combined analysis of five Finnish cohorts including 6,374 postmenopausal women examined whether adherence to three dietary quality indices—the modified Nordic Diet (mNDI), modified Mediterranean diet (mMEDI), and modified Alternative Healthy Eating Index (mAHEI)—was associated with breast cancer risk over an average 10-year follow-up during which 274 breast cancer cases were diagnosed. The study found a borderline protective association for the highest versus lowest adherence to the Nordic Diet (HR = 0.67; 95% CI 0.48-1.01), but no significant associations for the Mediterranean diet (HR = 0.88) or Alternative Healthy Eating Index (HR = 0.89). The authors note that the Nordic Diet, which is more aligned with local Finnish food culture, showed the strongest protective trend, though the association did not reach statistical significance. These findings suggest that while healthy dietary patterns have been linked to prevention of various chronic diseases, their relationship with postmenopausal breast cancer risk is not clearly established, with limited evidence for dietary factors beyond alcohol consumption affecting breast cancer risk.
2021
PLOS One
A case-control study in Ethiopia examined 50 breast cancer patients and 50 controls to investigate whether exposure to organochlorine pesticides is a risk factor for breast cancer in a low- and middle-income country context. Ten organochlorine pesticides were detected in participants’ serum, with heptachlor found at highest concentrations; mean serum levels of p,p’-DDE, p,p’-DDT, heptachlor, gamma-chlordane, endosulfan, and dibutyl-chlorendate were significantly higher in breast cancer patients than controls, and p,p’-DDT and gamma-chlordane emerged as significant predictors of breast cancer, with each unit increase in p,p’-DDT concentration doubling breast cancer odds (AOR = 2.03; 95% CI: 1.04-3.97) and each unit increase in gamma-chlordane tripling the odds (AOR = 3.12; 95% CI: 1.19-8.20). These findings suggest that organochlorine pesticide exposure may be a significant breast cancer risk factor in Ethiopia, where environmental contamination from these persistent organic pollutants remains a concern despite global restrictions. The study highlights the public health importance of reducing exposure to these banned or restricted pesticides in developing countries and emphasizes the need for continuous biomonitoring of persistent organic pollutants to inform disease prevention strategies and mitigation measures, particularly as breast cancer incidence rises in low- and middle-income countries where environmental regulation may be less stringent.
2021
Cancer Epidemiol Biomark Prev
A prospective study of 169,985 women from the Nurses’ Health Study cohorts followed over nearly 5 million person-years identified 12,482 invasive breast cancer cases and found that greater adherence to overall plant-based diets (PDI) and healthful plant-based diets (hPDI) was associated with 11% lower breast cancer risk (HR = 0.89 for both). The protective effect was strongest for ER-negative tumors, with women in the highest quintile of hPDI having 23% lower risk (HR = 0.77; 95% CI: 0.65-0.90) and those consuming the most healthy plant foods having 26% lower risk (HR = 0.74) of ER-negative breast cancer. This first prospective study examining healthful versus unhealthful plant-based dietary patterns suggests that high-quality plant-based diets may particularly protect against aggressive, hormone receptor-negative breast cancers.
2021
Int J Environ Res Pubilc Health
A case-control study of 494 breast cancer cases and 515 healthy controls in Poland’s Lodz region (2015-2019) found that night shift work was the third most important breast cancer risk factor after high BMI and short/no breastfeeding, ranking before early menstruation, late menopause, nulliparity, and smoking. Night work increased breast cancer risk 2.34-fold, with high-intensity night work showing an even greater 2.66-fold increase, and the harmful effects were influenced by intensity, frequency, rotation patterns, and cumulative years of night shift exposure. The findings support the IARC’s 2019 classification of night shift work as probably carcinogenic (Group 2A) and emphasize the need for ergonomic recommendations to minimize breast cancer risk among night shift workers through optimized scheduling practices.
2021
BMC Complement Med Ther
This study focused on the effect that tartrazine (E102), a common yellow food dye, had on the progression of breast cancer in rats that were exposed to 7,12-Dimethylbenz(a)anthracene (DMBA), a polycyclic aromatic hydrocarbons (PAH) that is widely known for its carcinogenicity. The researchers discovered that tartrazine accelerated the development and growth of tumors in the rats with 100% of rats having early incidents of breast cancer when exposed to both DMBA and tartrazin, and only 80% having early incidence when exposed to DMBA alone. The authors also hypothesized that tartrazine could cause oxidative stress, leading to DNA damage by producing Reactive Oxygen Species. These results may apply to humans as well, and raise concerns about the safety of prolonged or high-dose exposure to synthetic food dyes like tartrazine, especially in individuals who may already have other risk factors for cancer.
2021
Oncol Rep
A review of organophosphorus pesticides (OPs)—among the most commonly used insecticides—and their association with hormone-mediated cancer found that OPs combined with estrogen induce transformation events in human breast epithelial cells, with in vitro studies showing these substances cause genomic instability through inactivation of tumor-suppressor genes and activation of oncogenes. Studies using immortalized non-tumorigenic human breast epithelial cell lines (MCF-10F) demonstrated that OPs like malathion and parathion, particularly in the presence of estrogen, affect cell cycle regulation, epidermal growth factor signaling pathways, drug metabolism, and genomic stability, leading to cellular transformation and signs of carcinogenesis. The findings suggest hormone-mediated carcinogenic effects of these widely used insecticides on breast cancer risk in women, with experimental models revealing the multistep process by which normal breast cells transform into malignant ones through combined exposure to environmental pesticides and estrogen, providing mechanistic insights into how occupational and environmental OP exposure may contribute to breast cancer development.
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.
2021
Ocup Environ Med
A large Danish registry-based case-control study of 38,375 women under age 70 with primary breast cancer and matched controls used objective lifetime employment histories from the Danish Supplementary Pension Fund Register and a job exposure matrix to assess occupational ultraviolet radiation (UVR) exposure as a reliable measure of long-term solar UVR exposure. While no overall association was observed between occupational UVR exposure and breast cancer risk, among women aged ≥50 years, longer duration of UVR exposure (≥20 years: OR=0.83; 95% CI: 0.75-0.92) and highest cumulative exposure (OR=0.89; 95% CI: 0.83-0.95) were inversely associated with breast cancer risk, with no notable differences by estrogen receptor status. These findings suggest that long-term occupational UVR exposure may protect against late-onset breast cancer, supporting the hypothesis that solar UVR (likely through vitamin D production) may have protective effects on breast cancer development, particularly in postmenopausal women, though the mechanism requires further investigation in future occupational studies with objective exposure assessment.
2021
Cancers
A meta-analysis of 42 case-control studies published 2009-2020 including 110,580 women (30,778 breast cancer cases, 79,802 controls) from PubMed, Embase, and Cochrane Library databases examined the association between oral contraceptive (OC) use and breast cancer risk. OC use was associated with a significantly increased breast cancer risk (OR=1.15; 95% CI: 1.01-1.31; p=0.0358), with additional significant risk factors including early menarche, nulliparity, non-breastfeeding, older age at first birth, postmenopause, obesity, smoking, and family history of breast cancer. Despite this meta-analysis and extensive previous studies supporting the conclusion that oral contraceptive pills modestly increase breast cancer risk by approximately 15%, the relatively small effect size, heterogeneity across studies, and authors’ call for further confirmation indicate that the relationship between contemporary OC formulations and breast cancer requires continued investigation, particularly regarding dose-response relationships, specific formulation types, and timing of exposure relative to reproductive events.
2021
Environ Res
A prospective cohort study of 16,941 Danish nurses followed from 1993/1999 through 2012 (745 breast cancer cases during 320,289 person-years) examined residential outdoor light at night (LAN) exposure using satellite data and found no overall association between LAN and breast cancer risk in fully adjusted models accounting for individual characteristics, traffic noise, and air pollution, with hazard ratios of 0.97 (95% CI: 0.77-1.23) for highest LAN exposure and 1.09 (95% CI: 0.90-1.31) for medium exposure compared to lowest tertile. A suggestive association was observed between LAN and estrogen receptor-negative (ER-) breast cancer, though this was not statistically significant. Despite mechanistic evidence from melatonin research and xenograft experiments suggesting that light at night exposure may disrupt circadian rhythms and increase breast cancer risk, this large prospective study found only weak evidence for such an association using objective outdoor LAN measurements, though the study was limited to outdoor residential exposure and may not capture indoor lighting exposure or occupational night work that could be more relevant to circadian disruption and breast cancer development.
2020
Alcohol Alcohol
A meta-analysis of 22 cohort studies including 45,350 breast cancer cases found that each 10 grams per day increase in alcohol consumption (approximately one standard drink) was associated with a 10.5% increased breast cancer risk overall, with postmenopausal women showing an 11.1% increased risk per 10 grams daily. Wine showed a similar dose-response relationship (8.9% increased risk per 10g/day), while beer and spirits did not show significant linear associations in the dose-response analysis, and the risk was particularly elevated for estrogen receptor-positive (ER+) breast cancers. The alcohol-attributable percentage of breast cancer cases was highest in Europe compared to North America and Asia, suggesting that current drinking recommendations may need to explicitly address breast cancer risk, particularly for postmenopausal women and wine drinkers.
2020
Nutr J
A case-control study of 350 breast cancer patients and 700 controls in Iran found that women with the healthiest combined lifestyle scores—encompassing diet quality, physical activity, and non-smoking—had a 38% reduced breast cancer risk compared to those with the least healthy scores, with effects particularly pronounced in postmenopausal women who showed a 44% risk reduction. Notably, when examining individual lifestyle components, diet quality (measured by the Healthy Eating Index-2010) emerged as the strongest protective factor with a 46% risk reduction in the highest versus lowest category, while physical activity and smoking individually showed no significant associations. These findings suggest that comprehensive healthy lifestyle patterns—particularly high-quality diet—may substantially reduce breast cancer risk in postmenopausal women, though the lack of association in premenopausal women and the dominance of diet over other factors highlights the need for prospective studies to clarify whether combined lifestyle interventions offer synergistic benefits or whether specific components (like diet) drive most of the protective effect.
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.
2020
Eur J Clinic Nutr
A prospective cohort study in the Multiethnic Cohort found no direct associations between four widely-used diet quality indexes—including the Healthy Eating Index 2015, Alternate Healthy Eating Index 2010, alternate Mediterranean diet score, and DASH diet—and breast cancer risk when comparing highest versus lowest quintiles of adherence. However, overweight and obesity were significantly associated with breast cancer incidence, suggesting that diet quality may influence breast cancer risk indirectly through its effects on body weight rather than through direct mechanisms. These findings indicate that the breast cancer prevention benefits of healthy dietary patterns may operate primarily through weight management pathways, highlighting that maintaining healthy body weight through diet—rather than specific dietary patterns per se—may be the critical factor for breast cancer prevention, and underscoring the importance of comprehensive lifestyle interventions that address both diet quality and weight control rather than focusing on dietary patterns alone.
2020
Environ Res
A systematic review of 100 publications across 56 epidemiologic studies found that research enriched with women at higher baseline breast cancer risk—through family history, early-onset disease, or genetic susceptibility—consistently showed stronger and more frequent associations between environmental chemical exposures and breast cancer compared to average-risk populations. Specifically, 80% of studies enriched with family history or early-onset cases showed significant associations with exposures including PAHs, air pollution, DDT, PCBs, PFAS, metals, personal care products, and occupational chemicals, while 74% of studies examining genetic susceptibility found significant gene-environment interactions for various pollutants in women with variants affecting carcinogen metabolism, DNA repair, and oxidative stress. These findings suggest that the inconsistent evidence for environmental chemicals and breast cancer in the literature may partly stem from studying predominantly average-risk populations who may be less susceptible to environmental carcinogens, highlighting the critical need for future research to focus on high-risk populations and measure exposures during key windows of susceptibility (puberty, pregnancy, menopause) to more accurately capture the role of environmental chemicals in breast cancer development.
2020
Medicine
A meta-analysis of 6 studies found that exposure to solar ultraviolet (UV) radiation was associated with a 30% reduced breast cancer risk overall, with a dose-response analysis showing a linear protective relationship in women over 40 (14% risk reduction per unit increase in UV exposure). Notably, not tanning and covering the limbs were associated with increased breast cancer risk, while sunscreen use showed no association with risk, suggesting that actual UV skin exposure—rather than ambient UV levels alone—may be the key protective factor. This is the first dose-response meta-analysis demonstrating that higher UV exposure correlates with lower breast cancer risk in a linear fashion among middle-aged and older women, likely through Vitamin D production, though the findings highlight the complex balance between skin cancer risks from excessive UV exposure versus potential breast cancer protection from adequate sun exposure, and the need for further research on how factors like estrogen receptor status, Occupation, and ethnicity modify this relationship.
2020
J Natl Cancer Inst
A prospective study of 146,326 women in the UK Biobank found that maintaining a healthy lifestyle—combining favorable diet, physical activity, healthy weight, limited alcohol, and no smoking—was associated with 22% and 31% reduced breast cancer risk in premenopausal and postmenopausal women respectively, even among women with high genetic risk (top third of polygenic risk score). Importantly, women with high genetic risk who maintained favorable lifestyles still achieved 27-32% risk reductions across menopausal groups, and while high genetic risk doubled breast cancer risk overall, lifestyle factors provided consistent protective benefits regardless of genetic predisposition. These findings demonstrate that genetic risk is not destiny: even women with the highest genetic susceptibility to breast cancer can substantially reduce their risk through modifiable lifestyle factors, supporting the critical importance of population-wide lifestyle interventions for breast cancer prevention and providing hope that women at elevated genetic risk can take meaningful action to lower their cancer risk through behavioral changes.
2020
Int J Cancer
A nested case-control study within a large European cohort of 430 breast cancer cases and 645 controls found that while alcohol consumption was associated with a 17% increased overall breast cancer risk (36% for ER-positive tumors), individual sex hormones showed limited evidence of mediating this relationship except for a weak effect through free estradiol. However, when researchers used a sophisticated statistical approach (partial least squares regression) to create an alcohol-related hormonal signature—characterized by lower SHBG and higher estradiol and testosterone—this hormonal pattern was associated with 25% increased breast cancer risk and mediated approximately 24% of the alcohol-breast cancer association. These findings suggest that alcohol increases breast cancer risk partly through a complex hormonal mechanism involving the interplay of multiple sex hormones rather than through individual hormones alone, providing new mechanistic insight into how alcohol consumption drives breast carcinogenesis in postmenopausal women and supporting recommendations to limit alcohol intake for breast cancer prevention.
2020
Int J Environ Res Public Health
A case-control study of 494 breast cancer patients and 515 healthy women in Poland found that night-shift work was associated with a 161% increased breast cancer risk, even after adjusting for other cancer risk factors including BMI, smoking, reproductive history, age, location, and education. While 51.9% of breast cancer cases had a history of shift work compared to 34.1% of controls (108% increased risk overall), further analysis revealed that only night shifts—not other shift patterns—significantly increased risk, showing a 120% increased risk after adjustment for confounders. Given that Poland has a high percentage of night-shift workers and the dramatically elevated cancer risk observed, the authors call for government action on prophylactic measures and workplace policies to protect this vulnerable population from occupational cancer hazards.
2020
Medicina
A systematic review of 12 studies examining nurses and shift work found that most studies showed an association between breast cancer and consecutive rotating night shifts prolonged over time, with risk increasing particularly during early adulthood and after 5 or more years of working 6 or more consecutive night shifts. The review identified disruption of circadian rhythm and alterations in peripheral clock genes and reproductive hormones as key mechanisms linking night shift work to breast cancer development, with potential roles for melatonin suppression and epigenetic changes including telomere alterations. These findings are particularly concerning given that nursing is a predominantly female profession requiring 24-hour staffing, suggesting the need for workplace policies that limit consecutive night shifts and total years of night work exposure, along with further research to establish definitive causal mechanisms and identify protective strategies for the millions of women working night shifts globally.
2020
Env Health Persp
A systematic review and meta-analysis of 14 studies found that spending one or more hours per day in the sun during summer months was associated with a 16% reduced breast cancer risk compared to less than one hour daily, with similar protective effects observed for both 1-2 hours and more than 2 hours of sun exposure. Sun exposure during adolescence appeared particularly protective (17% risk reduction), while exposure after age 45 showed no significant benefit, and interestingly, ambient UV radiation levels alone were not associated with breast cancer risk. These findings suggest that active sun exposure—likely through Vitamin D production—may offer modest breast cancer protection when obtained regularly during youth and early adulthood, though the results should be balanced against known skin cancer risks from excessive UV exposure.
2020
Eu J Epidemiol
A large prospective study of over 300,000 Chinese women followed for 10 years found no association between moderate soy intake (averaging 9.4 mg/day of soy isoflavones) and breast cancer risk, even when comparing the highest (19.1 mg/day) to lowest (4.5 mg/day) intake groups. However, a meta-analysis combining this study with other prospective cohorts found that each 10 mg/day increase in soy isoflavone intake was associated with a modest 3% reduction in breast cancer risk. These findings suggest that while moderate soy consumption typical of Chinese diets appears safe and not associated with increased breast cancer risk, higher intakes may provide modest protective benefits, contrasting with earlier concerns about soy and breast cancer and supporting the traditional consumption of soy foods as part of a healthy diet.
2020
Breast Cancer Res Treat
A prospective cohort study of 57,654 Swedish women aged 40-74 years found that increased alcohol consumption was associated with a 26% higher breast cancer risk, but importantly, this relationship—and the protective effect of physical activity—was consistent across women regardless of their baseline breast cancer risk level. The study used the Tyrer-Cuzick model to categorize women as below average, average, or above average risk and found that additional risk factors (such as family history, reproductive factors, or breast density) did not modify how alcohol and physical activity affected breast cancer risk. These findings support recommending reduced alcohol consumption and increased physical activity for breast cancer prevention in all women, regardless of their individual risk profile, since the lifestyle benefits apply equally whether a woman is at low, average, or high baseline risk of developing the disease.
2020
Food Chem Tox
This article discusses the harmful impacts of polycyclic aromatic hydrocarbons (PAHs) found in deep-fried foods. It highlights their endocrine-disrupting, genotoxic, and carcinogenic abilities when oils used for deep frying are heated repeatedly or at high temperatures. PAHs disrupt steroidogenic pathways which can lead to hormonal imbalances of estrogen and testosterone causing lower sperm quality, estrogenic effects, and endocrine related disorders. Furthermore, PAHs are linked to increased cancer risks through genotoxicity which can cause mutations in the cell. Organ sites that can be affected by this cancer risk are the breast, prostate, colorectal, renal, and pancreas.
2020
Pharmacol Res
A comprehensive review of 10 studies including over 3.7 million individuals found that people who had ever used oral antibiotics had an 18% increased risk of breast cancer, with the association varying by antibiotic type—penicillin, tetracycline, and nitrofuran antibiotics showed the strongest links. The relationship appeared complex and possibly non-linear, with data hinting at increased risk with moderate antibiotic use but potential protective effects after 35 or more prescriptions, though this finding requires careful interpretation due to study limitations. It remains unclear whether antibiotics directly cause breast cancer or whether the association reflects other factors like underlying infections, immune function changes, or disruption of the gut microbiome, highlighting the need for further research into the mechanisms behind this relationship.
2020
PLOS One
A matched case-control study in Karachi, Pakistan examined 411 women with newly diagnosed breast cancer and 784 cancer-free controls to investigate the relationship between Vitamin D levels, supplementation, sun exposure, and breast cancer risk in a population where both Vitamin D deficiency and breast cancer are prevalent. The study found that women with Vitamin D deficiency (serum levels <20 ng/ml) had a 65% increased risk of breast cancer compared to those with sufficient levels (>30 ng/ml), while women who took Vitamin D supplements in the year prior had a 68% reduced risk of breast cancer. The researchers conclude that Vitamin D deficiency is associated with increased breast cancer risk in Pakistani women, and suggest that maintaining adequate Vitamin D levels through supplementation could be a safe, affordable prevention strategy. This approach may be particularly beneficial for reducing breast cancer incidence and mortality among economically disadvantaged women in Pakistan who face barriers to early detection and treatment, though further research is needed to confirm these findings.
2020
Nutrients
A prospective cohort study of 10,930 Spanish female university graduates in the SUN (“Seguimiento Universidad de Navarra”) project examined whether adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations was associated with breast cancer risk. The study used an 8-item score measuring compliance with recommendations including body fat, physical activity, consumption of wholegrains/vegetables/fruit/beans, avoidance of fast foods and processed meats, limited sugar-sweetened drinks and alcohol, and breastfeeding. While no significant association was found for overall breast cancer risk, women who scored highest on adherence (>5 points vs. ≤3 points) had a 73% reduced risk of postmenopausal breast cancer after adjusting for other variables. The findings suggest that following multiple WCRF/AICR lifestyle and nutritional recommendations together may significantly reduce postmenopausal breast cancer risk through their combined protective effects.
2020
Cancer Epidemiol Biomark Prev
A large international study of BRCA1 and BRCA2 mutation carriers conducted both retrospective (9,232 carriers) and prospective (3,886 carriers) analyses to examine whether tobacco smoking and alcohol consumption affect breast cancer risk in this high-risk population. The study found that smoking for more than 5 years before a first full-term pregnancy (FFTP) was associated with increased breast cancer risk in both BRCA1 carriers (19-36% increased risk) and BRCA2 carriers (25-30% increased risk) compared to women who never smoked, while other smoking variables and alcohol consumption showed no significant associations. These findings suggest that smoking specifically during the prereproductive years may increase breast cancer risk for BRCA mutation carriers, a finding that requires further investigation given its potential public health importance for this high-risk population. This represents the largest prospective study to date examining these lifestyle risk factors in women with BRCA mutations, who already face substantially elevated lifetime breast cancer risk.
2020
Int J Cancer
A prospective study of 42,012 women in the Sister Study followed participants for an average of 7.6 years and identified 1,536 invasive breast cancer cases to examine the association between meat consumption types and breast cancer risk. The study found that higher red meat consumption was associated with a 23% increased risk of invasive breast cancer (highest vs. lowest quartile), and when total meat consumption was held constant in a substitution model, replacing red meat with poultry reduced breast cancer risk by 28%. No associations were found between cooking practices, heterocyclic amines (carcinogens formed during high-temperature cooking), or heme iron from red meat and breast cancer risk, suggesting the red meat-breast cancer link may operate through other mechanisms. The findings suggest that women could potentially reduce their breast cancer risk by replacing red meat with poultry in their diets, though the biological mechanisms underlying this association require further investigation.
2020
Mol Cell Endocrinol
A review of EPA pesticide registration documents found that 28 pesticides cause mammary tumors in animals and five alter mammary gland development, yet the agency’s risk assessments often dismiss these findings or don’t evaluate their implications for breast cancer risk. Many of these pesticides work through hormone-disrupting pathways that could affect breast tissue, including common chemicals like malathion, atrazine, and triclopyr. The authors argue that current testing guidelines don’t adequately assess effects on the mammary gland and call for re-evaluation of several widely-used pesticides based on stronger standards informed by breast cancer biology.