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Circulating inflammatory biomarkers, adipokines and breast cancer risk-a case-control study nested within the EPIC cohort.

Cairat et al,

2022

BMC Med

A large European study measuring inflammatory markers in the blood of over 3,000 women found that inflammation’s relationship with breast cancer risk differs dramatically by menopausal status, with higher levels of leptin and C-reactive protein (CRP) appearing protective in premenopausal women but associated with increased risk in postmenopausal women. The opposing effects were particularly evident for leptin and CRP, which showed 11-17% lower breast cancer risk in premenopausal women but 10-16% higher risk in postmenopausal women, and these associations were influenced by body weight. These findings suggest that inflammation and obesity may affect breast cancer development through different biological mechanisms before and after menopause, highlighting the importance of considering menopausal status when assessing breast cancer risk factors.

Occupational exposure to organic solvents and breast cancer risk: a systematic review and meta-analysis.

Xiao et al,

2022

Environ Sci Poll Res

This meta-analysis of 24 studies found that women occupationally exposed to organic solvents (chemicals used in manufacturing, cleaning, and industrial processes) had an 18% increased risk of breast cancer compared to unexposed workers, with the association being particularly strong in postmenopausal women (35% increased risk) and European workers. Organic solvents are commonly found in workplaces involving paint, adhesives, dry cleaning, and manufacturing, and the increased risk was consistent across both large cohort studies and case-control studies. These findings suggest that workplace exposure to organic solvents is an important and preventable occupational health hazard that contributes to breast cancer risk, especially for women working in industries that regularly use these chemicals.

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

Amadou et al,

2021

Environ Int

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

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

Cohn et al,

2019

J Natl Cancer Inst

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

Use of dietary supplements containing soy isoflavones and breast cancer risk among women aged >50 y: a prospective study.

Touillaud et al,

2019

Am J Clin Nutr

A large French cohort study of 76,442 women over age 50 followed for 11 years found that current soy supplement use was associated with a 22% reduced risk of estrogen receptor-positive (ER+) breast cancer but a 101% increased risk of ER-negative breast cancer compared to never users. The risk profile varied significantly by personal characteristics: women with a family history of breast cancer showed a 36% increased risk with soy supplement use, while those without family history showed an 18% reduced risk; premenopausal or recently postmenopausal women showed a 50% risk reduction, while women more than 5 years past menopause showed a 6% increased risk. These findings suggest that soy supplements—often marketed as natural alternatives to hormone therapy—may have complex and opposing effects on breast cancer risk depending on tumor biology and individual characteristics, cautioning against their use particularly in women with breast cancer family history.

Specific microbiome patterns and their association with breast cancer: the intestinal microbiota as a potential biomarker and therapeutic strategy.

Amaro-da-Cruz et al,

2025

Clin Transl Oncol

A review of 29 studies found that breast cancer patients have distinct imbalances in their gut and breast tissue bacteria that vary based on cancer type, stage, menopause status, body weight, and physical activity, though no single bacterial profile has yet emerged as a reliable biomarker. The research suggests that gut microbiome composition may influence how well breast cancer treatments work, with some beneficial bacteria and their metabolites potentially improving therapy effectiveness or slowing tumor growth. These findings highlight the microbiome as a promising new area for developing personalized breast cancer treatments and improving outcomes, though more research is needed to identify specific bacterial targets and understand the underlying mechanisms.

BMI and breast cancer risk around age at menopause.

Von Holle et al,

2024

Cancer Epidemiol

A large collaborative study of 609,880 women from 16 prospective studies, including 9,956 breast cancer cases before age 55, examined when the relationship between body mass index (BMI) and breast cancer risk transitions from protective (before menopause) to harmful (after menopause). During the critical age window of 45-55 years, the study found that a five-unit BMI increment remained associated with reduced or neutral breast cancer risk across all menopausal status groups: HR=0.87 for premenopausal women, HR=1.00 for women after natural menopause, HR=0.99 after interventional loss of ovarian function, and HR=0.88 after hysterectomy without bilateral oophorectomy. The findings indicate that the well-documented reversal from BMI being protective to being a risk factor for breast cancer occurs after age 55, later than previously thought, suggesting that the transition to increased risk with higher BMI is not directly tied to the menopausal transition itself but occurs in the years following menopause. This timing provides important insight into how adiposity influences breast cancer risk across the lifespan and suggests that the hormonal and metabolic changes associated with higher BMI have different effects on breast tissue depending on age and years since menopause.

Association between processed and ultra-processed food intake and the risk of breast cancer: a case-control study.

Nouri et al,

2024

BMC Cancer

A case-control study of 133 breast cancer cases and 266 controls in Tehran, Iran used a food frequency questionnaire and the NOVA classification system to examine the association between processed foods (PFs) and ultra-processed foods (UPFs) consumption and breast cancer risk. In the initial model, women in the highest tertile of UPF consumption had nearly double the odds of breast cancer compared to the lowest tertile (OR = 1.93; 95% CI: 1.08-3.45), though this association was no longer significant after additional adjustments in a second model. However, when stratified by menopausal status, premenopausal women in the highest tertile of UPF consumption had more than 3.5 times higher odds of breast cancer (OR = 3.66; 95% CI: 1.33-10.08) in the fully adjusted model. These findings suggest that high consumption of ultra-processed foods may be particularly associated with increased breast cancer risk among premenopausal women, adding to the limited and sometimes contradictory evidence on the relationship between ultra-processed food intake and breast cancer.

Long-term weight change and risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

Ellingjord-Dale et al,

2022

Int J Epidemiol

A large European prospective study of 150,257 women followed for 14 years found that weight gain of more than 10 kg from age 20 to middle adulthood was associated with a 42% increased postmenopausal breast cancer risk among women who were lean at age 20, with the association present in both HRT users (23% increased risk) and non-users (40% increased risk) and particularly strong for ER+/PR+ breast cancers (46% increased risk). The findings indicate that maintaining stable weight from young adulthood is especially important for women who start out lean, as weight gain appears to negate the protective effect of lower early-life body weight. These results highlight a critical window for breast cancer prevention: while being lean in early adulthood is protective, this benefit is substantially diminished by subsequent weight gain, suggesting that weight management efforts should focus not just on current weight but on preventing long-term weight accumulation from young adulthood through menopause.

Mendelian randomization analyses of 23 known and suspected risk factors and biomarkers for breast cancer overall and by molecular subtypes.

Chen et al,

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.

How the Intensity of Night Shift Work Affects Breast Cancer Risk.

Szkiela et al,

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.

Association between overall diet quality and postmenopausal breast cancer risk in five Finnish cohort studies.

Männistö et al,

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.

Environmental exposures and breast cancer risk in the context of underlying susceptibility: A systematic review of the epidemiological literature.

Zeinomar et al,

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.

Mediation analysis of the alcohol-postmenopausal breast cancer relationship by sex hormones in the EPIC cohort.

Assi et al,

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.

Night Shift Work-A Risk Factor for Breast Cancer.

Szkiela et al,

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.

Adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research Recommendations and Breast Cancer in the SUN Project.

Barrios-Rodríguez et al,

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.

Microbial Alterations and Risk Factors of Breast Cancer: Connections and Mechanistic Insights.

Parida et al,

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.

Oral contraceptive and breast cancer: do benefits outweigh the risks? A case – control study from Jordan.

Bardaweel et al,

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.

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

Ding, et al.

2024

J Clin Endocrinol Metab

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

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