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2020
Breast Cancer Res Treat
A pilot study of 37 breast cancer patients found that women with HER2-positive breast cancer (an aggressive subtype) had 12-23% lower gut bacterial diversity and different bacterial compositions compared to HER2-negative patients, with less Firmicutes and more Bacteroidetes bacteria. The research also revealed that women who started menstruating early (age 11 or younger) and those with higher body fat had lower gut bacterial diversity, suggesting links between gut microbiome composition and known breast cancer risk factors. While the study was small, these findings indicate that gut bacteria composition may be connected to both breast cancer characteristics and established risk factors, warranting larger studies to better understand these relationships and their potential implications for prevention and treatment.
2020
Cells
A comprehensive review reveals that imbalanced gut and body microbiomes are linked to nearly all established breast cancer risk factors—including obesity, aging, periodontal disease, alcohol intake, reproductive history, and elevated estrogen levels—suggesting that microbial dysbiosis may itself be an important independent risk factor. The altered bacteria can promote cancer through multiple mechanisms: producing harmful metabolic byproducts, changing how the body processes medications and environmental chemicals, disrupting immune system function, and affecting how well cancer treatments work. These findings suggest that maintaining a healthy microbiome through diet, lifestyle, or therapeutic interventions could potentially reduce breast cancer risk and improve treatment outcomes, representing a promising new frontier in breast cancer prevention and management.
2020
Int J Mol Sci
The gut microbiome—trillions of bacteria living in the digestive tract—appears to influence breast cancer risk, treatment effectiveness, and likelihood of recurrence through its effects on metabolism, hormones, immune function, and brain signaling. While cancer treatments can disrupt the gut microbiome and contribute to negative side effects, research shows that the microbiome can be positively modified through diet, probiotic and prebiotic supplements, and exercise. This review synthesizes current evidence on the gut-breast cancer connection and highlights practical strategies for improving gut health that may lead to better treatment outcomes, fewer side effects, and improved overall wellbeing for breast cancer patients.
2020
Repro Toxicol
A 54-year follow-up study of 102 breast cancer cases and 310 matched controls among 9,300 daughters born 1959-1967 in the Child Health and Development Studies cohort found that high maternal perinatal levels of N-ethyl-perfluorooctane sulfonamido acetic acid (EtFOSAA, a precursor to PFOS) combined with high maternal cholesterol predicted a 3.6-fold increased breast cancer risk in daughters by age 52 (95% CI: 1.1-11.6), while maternal PFOS alone was paradoxically associated with decreased risk. These robust findings—consistent across alternative modeling approaches and independent of other maternal factors—demonstrate that prenatal exposure to specific PFAS compounds during critical developmental windows can influence breast cancer risk decades later, revealing multigenerational health consequences of persistent environmental chemicals. The results emphasize the critical importance of studying internal PFAS doses and chemical mixture exposures during vulnerable early-life periods for breast cancer prevention, particularly as current and future generations face continued ubiquitous exposure to these persistent compounds, though experimental validation and replication in additional epidemiological cohorts are needed to confirm causality and inform prevention strategies.
2020
Int J Cancer
A population-based case-control study of 3,030 breast cancer cases and 3,402 controls in Ontario, Canada found that iron intake’s effects on breast cancer risk varied by menopausal status, hormone receptor subtype, and antioxidant-related genotypes: among premenopausal women, dietary nonheme iron was positively associated with ER-/PR- breast cancer, while among postmenopausal women, supplemental iron reduced overall risk (OR=0.68; 95% CI: 0.51-0.91) but dietary heme iron increased ER-/PR- risk (OR=1.69; 95% CI: 1.16-2.47). GSTT1 and GSTM1/GSTT1 polymorphisms modified these associations, with higher dietary iron most strongly linked to increased risk among women with genetic deletions affecting antioxidant capacity (p<0.05). These findings suggest that iron's impact on breast cancer development through oxidative stress mechanisms depends on iron source (heme vs. nonheme, dietary vs. supplemental), menopausal status, tumor hormone receptor status, and individual genetic variation in oxidative stress defense.
2020
Environ Health
A nested case-control study of 197 incident postmenopausal breast cancer cases and 197 controls with blood samples collected 1994-1999 measured plasma levels of six PBDE congeners (BDE-28, -47, -99, -100, -153, -154) and PBB-153 using gas chromatography-mass spectrometry and found no overall evidence of association between brominated flame retardant (BFR) levels and breast cancer risk (log-concentrations yielding odds ratios of 0.87-1.07). Some analyses showed non-linear inverse associations for BDE-100 and BDE-153 with breast cancer risk (third vs. first quintile: OR=0.42; 95% CI: 0.19-0.93 and OR=0.42; 95% CI: 0.18-0.98, respectively) when exposure was modeled as ng/L plasma but not when lipid-adjusted (OR=0.58 and 0.53), with results unchanged by tumor hormone receptor status or BMI. These findings suggest no clear association between internal PBDE and PBB-153 levels and postmenopausal breast cancer risk, though limitations include small sample size, lack of genetic susceptibility information, single time-point exposure assessment that may not represent critical windows of susceptibility, and the paradoxical inverse associations requiring cautious interpretation, warranting additional larger studies with repeated measurements and assessment of early-life exposures to clarify the relationship between BFR exposure and breast cancer development.
2019
BMJ
A Mendelian randomization study using UK Biobank data (156,848 women including 7,784 breast cancer cases) and Breast Cancer Association Consortium data (122,977 cases, 105,974 controls) examined causal effects of sleep traits on breast cancer risk using genetic variants associated with chronotype, sleep duration, and insomnia symptoms. Two-sample MR analysis confirmed that morning preference reduced breast cancer risk by 12% per category increase (OR = 0.88; 95% CI: 0.82-0.93) and provided suggestive evidence that each additional hour of sleep duration increased risk by 19% (OR = 1.19; 95% CI: 1.02-1.39) for both ER+ and ER- breast cancer subtypes, with inconsistent evidence for insomnia symptoms. These findings—robust to sensitivity analyses accounting for horizontal pleiotropy—provide genetic evidence that being a “morning person” may protect against breast cancer while longer sleep duration may increase risk, suggesting that circadian rhythm patterns and sleep duration represent modifiable risk factors, though the counterintuitive finding regarding sleep duration requires further investigation given that adequate sleep is generally considered health-protective.
2019
J Expo Sci Environ Epidemiol
This study from a longitudinal cohort of 133 women diagnosed with breast cancer before age 50 and 133 age-matched controls without breast cancer. DDT is stored in adipose tissue, and the authors found that serum DDE (the main metabolite of DDT) was inversely associated with BMI amont women who were cancer-free, but that this association did not hold among women diagnosed with breast cancer before age 50. The authors suggest that early exposure to breast cancer among women exposed to DDT may be due to an uncoupling of the relationship between BMI and serum DDT, and that this may reveal biomarkers of risk through further research.
2019
Environ Res
This study investigated how DEHP (a common plastic additive) and its metabolite MEHP affect breast cancer-related markers in T-47D breast cancer cells exposed to various concentrations for 4 days. The researchers found that high-dose DEHP (10,000 nM) and low-dose MEHP (0.1 nM) significantly increased cell proliferation without causing cell death, and DEHP also increased progesterone receptor (PR) protein levels and nuclear accumulation. When cells were treated with a progesterone receptor blocker (Mifepristone), the increased cell growth was completely prevented and PR nuclear levels were partially reduced, indicating that DEHP promotes breast cancer cell proliferation through progesterone receptor activation. The findings suggest that DEHP exposure may increase breast cancer risk by activating progesterone signaling pathways, though the exact mechanisms and long-term consequences require further investigation.
2019
J Occup Environ Med
This case control study was conducted among Hispanic women agricultural workers who are exposed to pesticides. Chemicals associated with BC risk included organophosphates, organochlorines, and a phthalimide, Captan. The study concluded that agricultural work may be associated with increased BC risk in female Hispanic farm workers.
2019
JAMA Netw Open
A population-based cohort study of over 12 million South Korean youths (ages 0-19) followed from 2006-2015 found that exposure to diagnostic low-dose ionizing radiation was associated with a 64% increased overall cancer incidence, with computed tomography scans specifically showing a 54% increased risk. Among specific cancer types, breast cancer showed a particularly striking 132% increased incidence among exposed individuals, along with thyroid cancer (119% increase), myelodysplasia (148% increase), and other myeloid leukemias (114% increase), with risks remaining significant after adjusting for age and sex. These findings from over 1.2 million exposed children and adolescents who developed 1,444 cancers provide compelling evidence that even low-dose diagnostic radiation during childhood and adolescence—a critical window of susceptibility—substantially increases subsequent cancer risk, underscoring the urgent need for judicious use of radiation-based imaging in young people, adherence to ALARA principles (As Low As Reasonably Achievable), and careful consideration of alternative imaging modalities like ultrasound and MRI that don’t involve ionizing radiation.
2019
Chronobiol Int
A nested case-control study of 39,686 postmenopausal women in the California Teachers Study found that women with a definite evening chronotype (“night owls”) had a 20% increased breast cancer risk compared to definite morning chronotypes (“morning larks”), even after adjusting for established breast cancer risk factors. Importantly, this association was observed in a population without substantial night shift work history, suggesting that chronotype itself—the behavioral manifestation of an individual’s underlying circadian rhythm—may be an independent breast cancer risk factor beyond the effects of occupational circadian disruption. These findings raise the intriguing possibility that evening chronotypes may be more susceptible to environmental circadian disruption from factors like artificial light exposure, social jet lag (mismatch between biological and social timing), or irregular sleep-wake patterns, and warrant further investigation in other non-shift worker populations to confirm whether innate circadian preference represents a novel, modifiable risk factor for breast cancer through behavioral interventions targeting sleep timing and light exposure patterns.
2019
Eur J Clinic Nutr
A meta-analysis of seven observational studies including 319,993 participants found that women consuming the most pro-inflammatory diets (highest DII scores) had a 25% increased breast cancer risk compared to those with the least inflammatory diets, with particularly strong associations observed in postmenopausal women (15% increased risk) and hormone receptor-negative breast cancers (36% increased risk). The association varied by geography, showing dramatically elevated risk in Asian populations (130% increase) and more modest effects in European populations (26% increase), while case-control studies showed stronger associations (68% increase) than cohort studies. These findings reinforce that dietary patterns promoting chronic systemic inflammation—typically characterized by high intake of refined carbohydrates, red/processed meats, and trans fats with low intake of fruits, vegetables, and omega-3 fatty acids—contribute meaningfully to breast cancer risk, supporting dietary interventions focused on anti-inflammatory foods as a practical prevention strategy.
2019
Sci Rep
A Spanish case-control study of 973 breast cancer patients matched with controls found that the relationship between caloric intake and breast cancer risk varied dramatically by menopausal status: premenopausal women consuming 20% or more below their predicted caloric needs had a 64% reduced risk, while postmenopausal women consuming 40% or more above predicted needs had a 181% increased risk. For every 20% increase in relative caloric intake (observed versus predicted based on individual metabolism and activity), hormone receptor-positive and HER2-positive breast cancer risk increased by 13%, with triple-negative tumors showing a 7% increase per 20% caloric excess. These findings suggest that maintaining appropriate caloric intake matched to individual energy needs—and potentially moderate caloric restriction combined with regular physical activity—could be an effective breast cancer prevention strategy, particularly important given the different effects observed in pre- versus postmenopausal women.
2019
Breast Cancer Res Treat
A systematic review and meta-analysis of 11 cohort studies found that a history of stressful life events was associated with an 11% increased risk of breast cancer (pooled risk ratio: 1.11, 95% CI: 1.03-1.19). While the increase is modest, the finding suggests that psychological stress may play a role in breast cancer development and that women who experience significant life stressors could benefit from psychological and counseling services as a potential preventive measure. These results add to growing evidence linking chronic stress exposure to cancer risk and underscore the importance of addressing mental health and stress management as part of comprehensive breast cancer prevention strategies.
2019
Environ Pollut
This study investigated how three endocrine-disrupting chemicals (BPA, BBP, and DEHP) affect estrogen receptor alpha (ERα) activity under normal and low-oxygen (hypoxic) conditions in breast and endometrial cancer cells. The researchers found that BPA and BBP activated ERα at specific concentrations, while DEHP did not, but all three chemicals enhanced ERα-mediated gene activity and decreased ERα protein levels under hypoxic conditions. BPA and BBP also affected hypoxia-related factors, decreasing hypoxia-inducible factor-1 activity while increasing VEGF (a blood vessel growth factor) secretion in breast cancer cells, whereas DEHP had different effects. The findings suggest that these endocrine disruptors can alter ERα regulation under low-oxygen conditions, which may influence disease processes since hypoxia is common in tumors and other pathological states.
2019
PLOS One
Bisphenol AF (BPAF)—a chemical increasingly used to replace BPA in consumer products—shows even stronger estrogen-like effects than BPA and promotes the growth of estrogen receptor-positive (ER+) breast cancer cells through multiple hormone signaling pathways. Laboratory studies revealed that BPAF stimulates cancer cell proliferation by activating estrogen receptors and upregulating AREG, a growth-promoting gene, with blocking either estrogen receptors or AREG preventing BPAF’s cancer-promoting effects. These findings challenge the assumption that BPA alternatives are safer, demonstrating that BPAF may pose equal or greater breast cancer risks than the chemical it’s replacing, and highlight the urgent need for human studies to assess BPAF’s impact on breast cancer risk before its continued widespread use in products marketed as “BPA-free.”
2019
Environ Int
Advanced glycation end products (AGEs), formed during the processing of foods at high temperatures, act as endocrine disruptors and are linked to various health risks. These compounds accumulate in the body over time, promoting oxidative stress, aging, diabetes, and other degenerative diseases. Processed foods, often convenient and inexpensive, are significant sources of AGEs, contributing to hormonal disruption and potential long-term health effects. Choosing minimally processed, whole foods can help reduce exposure to these harmful compounds and support overall hormonal balance, reinforcing the importance of food quality in maintaining long-term health and well-being.
2019
Environ Int
A case-control study within the California Teachers Study examined 902 women with invasive breast cancer and 936 controls to assess whether serum levels of polybrominated diphenyl ethers (PBDEs)—common environmental contaminants with endocrine-disrupting properties—are associated with breast cancer risk. Blood samples were analyzed for three prevalent PBDE congeners (BDE-47, BDE-100, and BDE-153), with measurements taken an average of 35 months after cancer diagnosis. The study found no significant association between serum levels of any of the three PBDE congeners and breast cancer risk, even when stratified by menopausal status, tumor characteristics, or body weight. However, the authors note important limitations, including that post-diagnosis blood measurements may not reflect pre-diagnostic or lifetime exposures, and the study lacked information on genetic factors that could influence individual susceptibility.
2019
Int J Cancer
A meta-analysis of three nested case-control studies (CPS-II, EPIC-Italy, and NSHDS) including 1,435 breast cancer cases and 1,433 controls examined whether erythrocyte levels of cadmium and lead—both classified as carcinogens—were associated with breast cancer risk. Cadmium levels showed no association with breast cancer in the CPS-II cohort, inverse associations in the EPIC-Italy and NSHDS cohorts, and an overall inverse trend in the meta-analysis (continuous RR = 0.84; 95% CI 0.69-1.01), while large differences in lead distributions across studies prevented meta-analysis, and no individual study found associations between lead and breast cancer risk. These findings indicate that despite cadmium and lead being established carcinogens with persistent environmental presence and ubiquitous human exposure, circulating levels of these metals in adulthood were not associated with increased breast cancer risk in this large pooled analysis. The unexpected inverse association with cadmium observed in some cohorts requires further investigation to understand potential biological mechanisms or confounding factors.
2019
Int J Env Res Public Health
A French population-based case-control study (CECILE study) of 695 breast cancer cases and 1,055 controls measured plasma levels of organochlorine compounds (OCs)—p,p’-DDE and PCB153—at the time of diagnosis and used a physiologically-based pharmacokinetic (PBPK) model to estimate PCB153 exposure levels during adolescence (ages 11-20), when breast tissue may be particularly susceptible to hormonal disruption. The study found no clear association between measured OC levels at diagnosis and breast cancer risk overall, though there was a trend toward decreasing breast cancer odds ratios with increasing OC levels in women aged 50 and over; similarly, negative associations were observed between breast cancer and estimated adolescent PCB153 exposure levels. The PBPK modeling revealed that women born after 1960 had the highest estimated PCB153 exposures during adolescence (coinciding with peak environmental contamination), while older women had very low adolescent exposures, yet the unexpected negative associations between OC levels and breast cancer risk remained unexplained and may represent study artifacts. Despite these puzzling findings, the study demonstrates that PBPK models can be valuable tools in epidemiological research for back-estimating exposures during critical developmental windows, which could help address important questions about how early-life environmental exposures influence cancer risk decades later.
2019
Sci Rep
A case-control study of 1,050 breast cancer cases and 1,229 controls in which inflammatory markers (C-reactive protein and interleukin-6) were measured in 322 randomly selected case-control pairs examined whether dietary magnesium intake affects breast cancer risk directly and indirectly through inflammation. Higher magnesium intake was associated with 20% lower breast cancer risk (adjusted OR = 0.80; 95% CI: 0.65-0.99), while elevated CRP levels were associated with 43% increased risk (adjusted OR = 1.43; 95% CI: 1.02-2.01), though IL-6 showed no association with breast cancer. Path analysis revealed that dietary magnesium intake reduces breast cancer risk through two pathways: a direct protective effect and an indirect effect by lowering CRP levels, an inflammatory marker. These findings suggest that magnesium’s protective role against breast cancer operates both through anti-inflammatory mechanisms (by reducing systemic inflammation as measured by CRP) and through other direct biological pathways, highlighting the potential importance of adequate dietary magnesium intake for breast cancer prevention and the role of chronic inflammation in breast cancer development.
2019
Breast Cancer Res Treat
A case-control study within the MCC-Spain cohort examined 1,389 invasive breast cancer cases and 1,712 controls aged 20-85 years to investigate domain-specific associations between physical activity and breast cancer risk by menopausal status and molecular subtype. The study found unexpected results: occupational physical activity (OPA) intensity was associated with higher breast cancer risk, particularly for premenopausal women (OR = 1.89 for active/very active vs. sedentary jobs) and ER+/PR+, HER2- tumors (OR = 1.80), while sedentary time ≥6 hours/day increased postmenopausal breast cancer risk by 69%; conversely, moderate-to-high intensity household and recreational physical activity above 1,000 MET·min/week reduced breast cancer risk by 14-33% in both pre- and postmenopausal women. These findings reveal important distinctions between types of physical activity: while leisure-time and household physical activity provide protective benefits against breast cancer, occupational physical activity paradoxically showed positive associations with breast cancer risk—particularly for hormone receptor-positive tumors—which may reflect different biological mechanisms, exposure patterns, or confounding factors associated with Occupation. The study highlights that sitting time is an independent breast cancer risk factor regardless of other physical activity, and the surprising positive association between occupational physical activity and ER+/PR+ breast cancer warrants further investigation to understand underlying mechanisms.
2019
Medicine
A meta-analysis of 10 studies including 8,585 breast cancer cases among 686,305 participants examined the relationship between age at first oral contraceptive (OC) use and breast cancer risk through June 2018. The pooled analysis found a 24% increased breast cancer risk associated with earlier age at first OC use (RR = 1.24; 95% CI: 1.10-1.41), with a significant linear dose-response relationship indicating that younger age at first use was associated with higher breast cancer risk. However, subgroup analyses showed inconsistent results with no statistical significance when restricted to studies from Western countries, lower quality studies, smaller sample sizes, shorter follow-up periods, or when stratified by breast cancer subtypes defined by estrogen receptor (ER), progesterone receptor (PR), or HER2 status. The findings suggest that starting oral contraceptive use at a younger age may increase breast cancer risk in a dose-dependent manner, though this association appears to be influenced by study characteristics and may not differ consistently across hormone receptor-defined breast cancer subtypes, highlighting the need for further research to clarify these relationships and inform contraceptive counseling for young women.
2019
Int Arch Occup Environ Health
A systematic review and meta-analysis of 30 studies (with meta-analyses conducted on 13 studies) examined the association between occupational ethylene oxide (EO) exposure and risk of lympho-hematopoietic cancers (LHC) and breast cancer. The overall pooled meta-relative risk was 1.48 (95% CI: 1.07-2.05) for LHC and 0.97 (95% CI: 0.80-1.18) for breast cancer, with meta-RRs for LHC among EO production workers at 1.46 and sterilization workers at 1.07, neither reaching statistical significance. Notably, a clear temporal trend emerged showing substantially higher LHC risk estimates in earlier studies from the 1980s (meta-RR = 3.87) that progressively declined in more recent decades, with studies from the 2000s and 2010s showing meta-RRs of 1.05 and 1.19 respectively, neither statistically significant. The authors conclude that the most informative and methodologically rigorous epidemiological studies published in recent decades do not support an association between occupational ethylene oxide exposure and increased risk of either lympho-hematopoietic cancers or breast cancer, suggesting that earlier positive findings may have been influenced by methodological limitations, exposure misclassification, or confounding factors that have been better controlled in more recent research.
2019
Eur J Clinic Nutr
A meta-analysis of 23 prospective studies including 41,516 breast cancer cases and 1,171,048 individuals found that higher folate intake was associated with reduced risk of ER-/PR- breast cancer (RR = 0.82; 95% CI: 0.68-0.97), with each 100 μg/day increment decreasing risk by 6% for ER- and 10% for ER-/PR- subtypes. Additionally, high folate intake showed protective effects in premenopausal women (RR = 0.94) and individuals with moderate-to-high alcohol consumption (RR = 0.82), suggesting folate may be particularly beneficial for hormone receptor-negative breast cancers and specific high-risk populations.
2019
Molecules
A study examined the effects of four common herbicides (MCPA, mesotrione, bifenox, and dichlobenil) on breast cancer cells and found that these pesticides, which can remain as residues in plant-based foods, showed harmful effects on cancer cells at physiological concentrations. The researchers also tested whether traumatic acid (TA), a beneficial natural compound found in food, could counteract the effects of these herbicides when cells were exposed to both together. Results showed that TA, in a concentration-dependent manner, was able to influence and potentially reduce some of the effects of the tested herbicides on certain breast cancer cell lines. This research highlights concerns about herbicide residues in food as potential contributors to cancer risk while also suggesting that naturally occurring food compounds like traumatic acid might help mitigate some pesticide effects, though more research is needed to understand real-world implications.
2019
Environ Int
A systematic review of 342 peer-reviewed articles covering 202 unique chemicals used in consumer products analyzed exposure pathways, functional uses, product applications, exposure routes, and associated health risks, finding that phthalates, bisphenol-A, and polybrominated diphenyl ethers were the most frequently studied chemicals, with frequently reported uses including plasticizers, polymers/monomers, and flame retardants in food contact materials, personal care products, cosmetics, furniture, flooring, and electronics. The analysis revealed that publication volume on chemicals tends to surge following major regulatory changes or exposure incidents rather than before market introduction, indicating a reactive rather than proactive approach to chemical safety assessment. These findings highlight the critical gap between the increasingly diverse array of chemicals used in consumer products and our lagging understanding of their exposure pathways and human health risks, emphasizing the urgent need to develop capacity and mechanisms for identifying health risks prior to chemical releases rather than after exposure incidents or regulatory action, to enable preventive rather than reactive public health protection.
2019
Arch Med Res
A case-control study of 101 incident breast cancer cases and 101 matched controls at the Instituto de Seguridad Social del Estado de México y Municipios found that women who worked night shifts had 8.58-fold higher odds of breast cancer compared to those who never worked nights (OR=8.58; 95% CI: 2.19-33.8), while breastfeeding was protective (OR=0.12; 95% CI: 0.02-0.60) and early menarche ≤12 years increased risk (OR=18.58; 95% CI: 2.19-148). Despite the small sample size yielding wide confidence intervals, these findings from Mexican women are consistent with studies from other countries positively associating night shift work with breast cancer risk. The results support the hypothesis that night shift work involving circadian disruption increases breast cancer risk, though the large effect size and wide confidence intervals suggest the need for larger studies with more precise estimates to confirm these associations in Mexican populations.
2019
Am J Indust Med
A case-control study of 300 breast cancer cases and 300 age- and residence-matched controls in Morocco examined associations between occupation, industry, and breast cancer risk using detailed occupational histories (jobs held ≥6 months) coded by international standards (ISCO 08, Moroccan Analytical Classification, European Statistical Classification). Women doing only household work showed decreased breast cancer risk (OR=0.32; 95% CI: 0.18-0.55), while agricultural workers—particularly agricultural laborers—had significantly increased risk (OR=2.91; 95% CI: 1.51-5.60) with risk increasing by duration of employment (p-trend=0.01), findings corroborated by industry-level analyses. These results suggest that occupational exposures in agricultural work may substantially increase breast cancer risk among Moroccan women, warranting further investigation with advanced exposure assessment methods to identify specific chemical exposures (likely pesticides and other agricultural chemicals) driving this elevated risk and inform targeted prevention strategies and screening programs for this high-risk occupational group in populations where agriculture employs significant numbers of women.
2019
BMC Women's Health
A case-control study of 450 Jordanian women (225 cases, 225 controls) aged 18-65 examined associations between oral contraceptive (OC) use and breast cancer risk in a Middle Eastern population. Regular OC use was associated with more than double the breast cancer risk (OR=2.25; 95% CI: 1.34-2.79; p=0.002), though duration of use showed no significant association (p>0.05), with additional significant risk factors including age at puberty, age at menopause, pregnancy history, menopausal status, and family history of cancer. These findings suggest that regular oral contraceptive use may be associated with increased breast cancer risk in Jordanian women, though the lack of duration-response relationship is inconsistent with some other studies and the authors note that larger multi-center studies are needed to confirm these findings in the Middle Eastern female population where limited research on OC use and breast cancer has been conducted.
2018
PLOS One
This study investigated how phthalates affect the growth of normal breast cells (MCF-10A) when grown alongside breast fibroblasts derived from tissue near estrogen receptor (ER) positive and negative breast cancers. The researchers found that only fibroblasts from ER-positive breast cancer tissue significantly stimulated breast cell proliferation, and when these co-cultures were exposed to estrogen or three phthalates (BBP, DBP, DEHP), cell growth increased significantly along with markers of cell division and estrogen receptor expression. The effects of phthalates on normal breast cells were similar to those of estrogen and depended on estrogen receptor activity, suggesting that phthalates act through hormone-mediated pathways. The study concludes that phthalates should be considered potential endocrine disruptors with breast cancer risk implications, even at low concentrations, particularly in the presence of estrogen-responsive tissue.
2018
Tox Lett
This study investigated how butyl benzyl phthalate (BBP), a common environmental contaminant linked to breast cancer, promotes cancer cell growth and identified the molecular mechanisms involved. The researchers found that BBP increased proliferation in both estrogen receptor-positive (MCF-7) and negative (MDA-MB-231) breast cancer cells by promoting cell cycle progression and upregulating growth-promoting proteins while downregulating tumor suppressor proteins. For the first time, the study revealed that BBP works through modulating microRNA-19a/b, which targets the tumor suppressor gene PTEN, leading to activation of the AKT signaling pathway that promotes cell growth. These findings provide new insights into how BBP contributes to breast cancer development at the molecular level and suggest potential targets for intervention.
2018
Environ Res
A systematic review of 158 studies examining environmental chemicals and breast cancer found the strongest evidence for increased risk from exposures during critical developmental periods (in utero, adolescence, pregnancy) to DDT, dioxins, PFOSA, air pollution, and occupational solvents, with risk estimates ranging from 1.4 to 5 times higher. A landmark 50-year study that captured DDT exposure during windows of breast development showed particularly elevated risks, while research on genetic variations found that women with certain DNA repair gene variants had higher breast cancer risk from PAH (polycyclic aromatic hydrocarbon) exposure. However, most studies failed to assess exposure timing during biologically relevant windows of susceptibility, and many current-use chemicals in consumer products remain inadequately studied, with major challenges including reconstructing decades-old exposures and measuring rapidly metabolized chemicals in complex real-world mixtures.
2018
BMC Pub Health
A mixed ecological and case-control study in Australia found that obesity occurring between ages 31-40 was independently associated with a 250% increased breast cancer risk in middle-aged women, though no direct association was found between alcohol consumption and breast cancer in the case-control analysis despite ecological correlations. The study revealed that stress was ecologically linked to both alcohol consumption and obesity but not directly to breast cancer incidence, suggesting that stress may influence breast cancer risk indirectly through health behaviors rather than representing a “missing link” as hypothesized. These findings highlight a critical window for breast cancer prevention: obesity in the decade before age 40 appears particularly risky, supporting targeted weight management interventions for women in their 30s, while the complex interrelationships between stress, alcohol, obesity, and breast cancer warrant further investigation using longitudinal designs that can capture temporal sequences and cumulative exposures across women’s reproductive years.
2018
Nutr Cancer
A case-control study of 136 breast cancer patients and 272 controls in Iran found that women consuming the most pro-inflammatory diets (highest quartile of DII scores) had a 164% increased breast cancer risk compared to those with the least inflammatory diets, with the association particularly striking among premenopausal women who showed a 451% increased risk. No association was detected in postmenopausal women, contrasting with findings from other studies that have typically shown stronger effects in postmenopausal populations. These findings suggest that pro-inflammatory dietary patterns may be especially harmful during premenopausal years when breast tissue is more metabolically active and hormone-responsive, highlighting the potential importance of anti-inflammatory dietary interventions—emphasizing whole grains, fruits, vegetables, legumes, nuts, and fish while limiting processed foods, red meat, and refined carbohydrates—as a targeted prevention strategy for younger women at risk of breast cancer.
Dietary Inflammatory Potential Score and Risk of Breast Cancer: Systematic Review and Meta-analysis.
2018
Clinic Breast Cancer
A systematic review and meta-analysis of 9 studies including 296,102 participants found that higher dietary inflammatory potential was associated with a 14% increased breast cancer risk overall, though the association varied by study design with case-control studies showing stronger effects (63% increased risk, not statistically significant) than cohort studies (4% increased risk, not significant). The pooled analysis across all study types showed a significant positive association between pro-inflammatory diets and breast cancer, suggesting that dietary modifications to reduce inflammatory potential could meaningfully reduce breast cancer risk. These findings reinforce that chronic low-grade inflammation driven by diet—characterized by high intake of refined carbohydrates, red and processed meats, and trans fats with low consumption of anti-inflammatory foods like fruits, vegetables, whole grains, and omega-3 fatty acids—contributes to breast carcinogenesis, supporting dietary pattern interventions focused on anti-inflammatory foods as an accessible and modifiable prevention strategy for women.
2018
Maturitas
A Spanish population-based case-control study of 1,006 breast cancer cases and 1,370 controls found that high total meat intake was associated with a 39% increased breast cancer risk in postmenopausal women, with processed/cured meat showing a 47% increased risk overall and a striking 152% increased risk specifically for triple-negative breast cancers. Cooking methods and doneness preferences significantly modified risk: well-done red meat was associated with 62% increased risk and stewed red meat with 49% increased risk (particularly for hormone receptor-positive tumors), while pan-fried or breaded white meat showed 38% increased overall risk and 78% increased risk in premenopausal women. These findings suggest that breast cancer risk could be reduced not only by limiting meat consumption—especially processed meats—but also by modifying cooking practices to avoid well-done or high-temperature cooking methods that generate carcinogenic compounds like heterocyclic amines and polycyclic aromatic hydrocarbons.
2018
Breast Cancer Res Treat
A meta-analysis of 25 epidemiological studies (23 cohort studies and 2 randomized trials) found that hormone replacement therapy (HRT) was associated with a 33% increased breast cancer risk overall, with combined estrogen-progestin therapy (EPT) showing stronger associations than estrogen-only therapy (ET). EPT was associated with both ductal (51% increased risk) and lobular breast cancer (38% increased risk), and all HRT types were linked to ER-positive but not ER-negative breast cancers, consistent with hormone-driven carcinogenesis. Notably, Asian women using HRT showed higher breast cancer risk than Western women, possibly due to differences in baseline hormone levels, genetic susceptibility, body composition, or HRT formulations used—a finding highlighting the importance of considering racial and ethnic differences when counseling women about menopausal hormone therapy risks and benefits.
2018
PLOS One
A case-control study of 399 breast cancer patients with receptor status information and 324 controls found that current menopausal hormone therapy (MHT) use was associated with approximately double the risk of hormone receptor-positive breast cancers, including ER+ (104% increased risk), ER+/PR+ (129% increased risk), and notably ER+/PR+/HER2- subtypes (130% increased risk). Past MHT use showed no elevated risk for any subtype, and current use was not significantly associated with hormone receptor-negative cancers, indicating the effect is specific to hormonally-driven tumors. These findings provide mounting evidence that MHT specifically increases risk of the ER+/PR+/HER2- subtype—the most common breast cancer type—adding to concerns about current hormone therapy use and supporting the need for women and clinicians to carefully weigh the duration of MHT treatment against cardiovascular and quality-of-life benefits versus breast cancer risks.
2018
Cancer Epidemiol Biomark Prev
A systematic review and meta-analysis of 24 studies found suggestive evidence that physical activity may reduce breast cancer risk through increased global DNA methylation, with higher activity levels showing a trend toward higher methylation (19% standardized mean difference) and higher methylation associated with a 30% reduced breast cancer risk, though neither association reached statistical significance overall. Subgroup analyses revealed that the protective pathway became clearer when examining long-term physical activity patterns and prospective cohort studies specifically, where both associations were statistically significant. This is the first systematic review to examine the complete biological pathway linking physical activity to breast cancer prevention through epigenetic mechanisms, suggesting that exercise may alter DNA methylation patterns in ways that protect against cancer development—a finding that could help explain how physical activity exerts its well-established cancer-preventive effects at the molecular level.
2018
Eur J Public Health
A 34-year study in Italy’s Veneto Region, where drinking water was contaminated with PFAS chemicals from a manufacturing plant operating since 1964, found significantly higher mortality rates in contaminated communities compared to uncontaminated areas for multiple diseases including diabetes, heart disease, stroke, Alzheimer’s, and breast cancer in women. Women in PFAS-contaminated areas showed elevated mortality from kidney cancer, breast cancer, and Parkinson’s disease, while both men and women had increased deaths from cardiovascular and metabolic diseases. These population-level findings suggest PFAS exposure—from widespread “forever chemicals” used in nonstick cookware, food packaging, stain-resistant fabrics, and firefighting foam—may increase risks for multiple serious diseases including breast cancer, though individual-level studies are needed to confirm causal relationships and understand the mechanisms behind these health impacts.
2018
Oncol Rep
This study investigated whether exposure to bisphenol A (BPA) and phthalate metabolites affects breast cancer risk through epigenetic changes in the ADAM33 gene, which plays a role in cancer progression. The researchers conducted a case-control study with 44 breast cancer patients and 22 controls, analyzing ADAM33 gene methylation patterns in blood samples and measuring urinary concentrations of endocrine-disrupting chemicals. They found that certain phthalate metabolites (MEHHP, MECPP, MEOHP) were positively associated with increased methylation of the ADAM33 gene, which was linked to higher gene expression levels. Surprisingly, the study suggests these phthalate metabolites may have a protective effect against breast cancer by increasing ADAM33 methylation and expression, contrary to the typical expectation that endocrine disruptors increase cancer risk.
2018
Food Chem Tox
A systematic review of 25 studies examining phthalates (plastic chemicals) and breast cancer found that while laboratory studies show certain phthalates can activate estrogen receptors and promote cancer cell growth, epidemiological studies in humans have produced mixed and inconclusive results. The main source of phthalate exposure is through diet—particularly from food and beverages in plastic packaging—but current human studies have significant limitations in how they measure exposure and account for other risk factors. The review calls for better-designed future studies that use hair samples instead of urine for more accurate long-term exposure assessment, include dietary factors and genetic markers as confounders, and investigate phthalates’ effects beyond just estrogen-driven cancers to include all breast cancer subtypes.
2018
Environ Int
A study of 54 female cashiers in South Korea found that handling thermal paper receipts without gloves doubled their urinary BPA levels during work shifts, but wearing gloves completely prevented this increase in exposure. Higher BPA levels were associated with elevated fasting insulin and insulin resistance, markers of metabolic dysfunction that can lead to diabetes and cardiovascular disease. The findings demonstrate that cashiers face significant occupational BPA exposure from receipt handling and that simple protective measures like wearing gloves can effectively eliminate this exposure route, offering an immediate and practical intervention to protect workers’ health.
2018
Biomed Res Int
A case-control study of 116 women with newly diagnosed breast cancer and 226 controls used dual-energy X-ray absorptiometry to examine the relationship between body composition, physical activity, and breast cancer risk, analyzing results separately by menopausal status. In premenopausal women, higher total body fat percentage, android (abdominal) fat, and waist circumference were associated with increased breast cancer risk, while higher lean body mass and greater physical activity were protective; among postmenopausal women, physical activity reduced breast cancer risk by 49%. The study concludes that low lean body mass and high abdominal fat increase breast cancer risk in premenopausal women, while regular physical activity is protective against breast cancer in both pre- and postmenopausal women. These findings suggest that maintaining healthy body composition through physical activity may be an important breast cancer prevention strategy across all life stages.
2018
Breast Cancer Res Treat
A study of 27,153 postmenopausal women in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial created an estrogen-related lifestyle score (ERLS) combining four factors: estrogenic diet, alcohol intake, body mass index (BMI), and physical activity, with scores ranging from 0-6 and higher scores representing lower estrogenic lifestyle patterns. Women with ERLS scores of 4 or ≥5 had 23% and 34% lower breast cancer risk, respectively, compared to those with scores ≤2, with similar protective effects observed for invasive cases and estrogen receptor-positive subtypes. The findings indicate that adopting multiple low-estrogen lifestyle behaviors together—including a low estrogenic diet, minimal alcohol consumption, healthy body weight, and high physical activity—has a combined protective effect against postmenopausal breast cancer that is stronger than any single factor alone. The researchers suggest this combined effect likely works by influencing estrogen metabolism, highlighting the importance of addressing multiple lifestyle factors simultaneously for breast cancer prevention in postmenopausal women.
2018
Breast Cancer Res
A pooled analysis of three population-based case-control studies including 6,320 women (3,934 cases, 2,386 controls) aged 35-64 years examined whether the associations between body mass index (BMI) and breast cancer risk differ by tumor subtype defined by estrogen receptor (ER), progesterone receptor (PR), and HER2 status. Higher BMI at age 18 was inversely associated with premenopausal breast cancer risk across all ER/PR/HER2 subtypes (≥25 vs. <20 kg/m²: OR=0.72), with the strongest protection seen in premenopausal women who had high BMI both at age 18 and currently (46% reduced risk; OR=0.54; 95% CI: 0.38-0.78), while no significant associations were found for postmenopausal breast cancer. The findings indicate that high BMI during late adolescence provides similar protective effects against all molecular subtypes of premenopausal breast cancer regardless of hormone receptor or HER2 status, and this protection appears to be maximized when women maintain higher BMI consistently throughout their premenopausal years. These results suggest that the mechanisms by which adiposity protects against premenopausal breast cancer operate broadly across different tumor subtypes rather than being specific to hormone receptor-positive disease.
2018
Environ Health
A nested case-control study within the California Teachers Study examined 902 women with invasive breast cancer and 858 controls who provided blood samples an average of 35 months after case diagnosis to assess whether serum concentrations of six per- and poly-fluoroalkyl substances (PFASs)—PFOA, PFNA, PFUnDA, PFHxS, PFOS, and MeFOSAA—were associated with breast cancer risk. For all invasive breast cancers combined, none of the adjusted odds ratios were statistically significant, though marginally significant inverse associations were observed for PFUnDA and PFHxS; statistically significant inverse associations for these two compounds were found only among the 107 women with hormone receptor-negative tumors, not among the 743 with hormone-positive tumors. The authors conclude that the study provides no evidence that post-diagnosis serum PFAS levels are related to breast cancer risk, and suggest that the few inverse associations observed may be due to chance or study design artifacts, particularly because measurements were taken after diagnosis rather than before. Future research should include pre-diagnosis PFAS measurements, genetic susceptibility factors, and endogenous estrogen levels to better assess whether these widely used synthetic chemicals—some of which are known mammary toxicants and endocrine disruptors—influence breast cancer development.
2018
Eur J Obstet Gynecol Repod Biol
A hospital-based case-control study of 134 breast cancer cases and 267 controls in Tehran, Iran used a 168-item food frequency questionnaire and factor analysis to identify two major dietary patterns and assess their association with breast cancer risk. The “healthy” pattern (high in fruits, vegetables, seeds, legumes, fish, whole grains, and liquid/olive oils, with low salt) showed no significant association with breast cancer (OR: 0.83), while the “unhealthy” pattern (high in sweets, soft drinks, mayonnaise, solid oils, processed meat, fried/boiled potatoes, and salt) was associated with significantly increased breast cancer risk in the highest versus lowest quartile (OR: 2.21; 95% CI: 1.04-4.69). When stratified by menopausal status, the unhealthy dietary pattern showed a particularly strong association with breast cancer risk among postmenopausal women (OR: 3.56; 95% CI: 1.16-10.95), but not premenopausal women. These findings suggest that overall dietary patterns—rather than individual nutrients or foods—may be important determinants of breast cancer risk, with an unhealthy Western-style diet pattern characterized by processed foods, added sugars, unhealthy fats, and high salt intake potentially more than doubling breast cancer risk, especially in postmenopausal Iranian women.