Menstrual hygiene management among adolescent girls in West Africa: A systematic review.

A systematic literature review was conducted to examine all recent academic, peer-reviewed studies of menstrual hygiene management (MHM) across adolescent girls in Anglophone West Africa. The objective was to assess the status of the scholarship surrounding the knowledge, attitudes, and practices of MHM across English-speaking West African countries and identify gaps in the literature for further research. The authors searched the epidemiological literatures indexed in PubMed and cross-referenced bibliographies for studies published between 2010-2022. Of 59 abstracts and articles screened, 35 met the final inclusion criteria. Despite differences in study design, setting, and data sources, the study results concurred on an average age of menarche between 12-15 years old among adolescent girls. The knowledge of MHM came from multiple sources, most commonly mothers, female siblings, and teachers and higher knowledge was associated with age, source, wealth, religion, and education level. Less than half of the adolescent girls knew about menstruation before menarche. Many studies showed that girls were shocked by their first period and fearful of staining. Menstruation was associated with dysmenorrhea, fear/embarrassment, and missing school. The existing studies suggest that more implementation and evaluation of menstrual hygiene management materials, education, and facilities are needed to address the educational, physical, and social disparities that exist among girls in West African countries.

Une revue systématique de la littérature a été menée pour examiner toutes les études universitaires récentes évaluées par des pairs sur la gestion de l'hygiène menstruelle (MHM) chez les adolescentes d'Afrique de l'Ouest anglophone. L'objectif était d'évaluer l'état de la recherche sur les connaissances, les attitudes et les pratiques de la GHM dans les pays anglophones d'Afrique de l'Ouest et d'identifier les lacunes dans la littérature pour des recherches plus approfondies. Les auteurs ont recherché dans la littérature épidémiologique indexée dans PubMed et des bibliographies croisées pour les études publiées entre 2010 et 2022. Sur les 59 résumés et articles examinés, 35 répondaient aux critères d'inclusion finaux. Malgré les différences dans la conception, le cadre et les sources de données de l'étude, les résultats de l'étude concordaient sur un âge moyen des premières règles entre 12 et 15 ans chez les adolescentes. La connaissance de la GHM provenait de sources multiples, le plus souvent des mères, des frères et sœurs et des enseignants, et les connaissances supérieures étaient associées à l'âge, à la source, à la richesse, à la religion et au niveau d'éducation. Moins de la moitié des adolescentes connaissaient leurs règles avant les premières règles. De nombreuses études ont montré que les filles étaient choquées par leurs premières règles et craignaient les taches. Les menstruations étaient associées à la dysménorrhée, à la peur/à la gêne et à l'absence à l'école. Les études existantes suggèrent qu'une plus grande mise en œuvre et une plus grande évaluation du matériel, de l'éducation et des installations de gestion de l'hygiène menstruelle sont nécessaires pour remédier aux disparités éducatives, physiques et sociales qui existent parmi les filles dans les pays d'Afrique de l'Ouest.

Reproductive risk factors for breast cancer and association with novel breast density measurements among Hispanic, Black, and White women.

PURPOSE: There are differences in the distributions of breast cancer incidence and risk factors by race and ethnicity. Given the strong association between breast density and breast cancer, it is of interest describe racial and ethnic variation in the determinants of breast density. METHODS: We characterized racial and ethnic variation in reproductive history and several measures of breast density for Hispanic (n = 286), non-Hispanic Black (n = 255), and non-Hispanic White (n = 1694) women imaged at a single hospital. We quantified associations between reproductive factors and percent volumetric density (PVD), dense volume (DV), non-dense volume (NDV), and a novel measure of pixel intensity variation (V) using multivariable-adjusted linear regression, and tested for statistical heterogeneity by race and ethnicity. RESULTS: Reproductive factors most strongly associated with breast density were age at menarche, parity, and oral contraceptive use. Variation by race and ethnicity was most evident for the associations between reproductive factors and NDV (minimum p-heterogeneity:0.008) and V (minimum p-heterogeneity:0.004) and least evident for PVD (minimum p-heterogeneity:0.042) and DV (minimum p-heterogeneity:0.041). CONCLUSION: Reproductive choices, particularly those related to childbearing and oral contraceptive use, may contribute to racial and ethnic variation in breast density.

Impact of age, race, and family history on COVID-19-related changes in breast cancer screening among the Boston mammography cohort study.

PURPOSE: We studied women enrolled in the Boston Mammography Cohort Study to investigate whether subgroups defined by age, race, or family history of breast cancer experienced differences in the incidence of screening or diagnostic imaging rates during the COVID-19 lockdown and had slower rebound in the incidence of these rates during reopening. METHODS: We compared the incidence of monthly breast cancer screening and diagnostic imaging rates over during the pre-COVID-19 (January 2019-February 2020), lockdown (March-May 2020), and reopening periods (June-December 2020), and tested for differences in the monthly incidence within the same period by age (< 50 vs ≥ 50), race (White vs non-White), and first-degree family history of breast cancer (yes vs no). RESULTS: Overall, we observed a decline in breast cancer screening and diagnostic imaging rates over the three time periods (pre-COVID-19, lockdown, and reopening). The monthly incidence of breast cancer screening rates for women age ≥ 50 was 5% higher (p = 0.005) in the pre-COVID-19 period (January 2019-February 2020) but was 19% lower in the reopening phase (June-December 2020) than that of women aged < 50 (p < 0.001). White participants had 36% higher monthly incidence of breast cancer diagnostic imaging rates than non-White participants (p = 0.018). CONCLUSION: The rebound in screening was lower in women age ≥ 50 and lower in non-White women for diagnostic imaging. Careful attention must be paid as the COVID-19 recovery continues to ensure equitable resumption of care.

COVID-19 infection and mortality among non-pregnant indigenous adults in Mexico 2020-2022: Impact of marginalisation.

Background: Indigenous individuals have higher rates of mortality and poverty in Mexico and more than half are marginalised, and COVID-19 pandemic aggravated the existing burden of health disparities. We aimed to analyse the effects of being indigenous and marginalised on coronavirus (COVID-19) infection fatality in Mexico. Methods: We identified 3 424 690 non-pregnant, COVID-19 positive adults ≥19 years in the Mexico national COVID-19 database with known date of symptom. We used demographic information, indigenous status, marginalisation status, and co-morbidities in binary logistic regression to predict mortality, adjusting for covariates, including hospitalisation, admission to the intensive care unit (ICU), and mechanical ventilation use. We also assessed the interaction between indigenous status and marginalisation. Results: Marginalisation was much higher among indigenous (53.7%) compared to non-indigenous individuals (4.8%). COVID-19 fatalities were approximately 20 years older (64.4 and 63.0 years) than survivors (44.7 and 41.2 years) among indigenous vs non-indigenous individuals, respectively. The unadjusted risk of COVID-19 fatality among indigenous individuals was nearly two-fold (odds ratio (OR) = 1.92)) compared to non-indigenous individuals (OR = 1.05). COVID-19 fatality was higher among highly marginalised individuals (upper quartile) (OR = 1.51; 95% confidence interval (CI) = 1.49-1.54). Marginalised indigenous individuals had a significantly lower likelihood of ICU admission compared to non-indigenous non-marginalised individuals. The likelihood of mechanical ventilation for indigenous individuals was 4% higher compared to non-indigenous individuals. Indigenous marginalised individuals had a significantly lower probability of mechanical ventilation compared to non-indigenous non-marginalised individuals. COVID-19 comorbidity risks of fatality significantly differed between the two groups in the Cox survival analysis. In the fully adjusted model, indigenous individuals were 4% more likely to die from COVID-19 compared to non-indigenous. Conclusions: Indigenous, marginalised individuals with COVID-19 had higher risk of hospitalisation and ICU admission than non-indigenous patients. Marginalised, indigenous individuals were less likely to receive mechanical ventilation compared to non-indigenous, but had a higher risk of COVID-19. Indigenous individuals had a 4% higher COVID-19 mortality risk COVID-19 compared to non-indigenous individuals. Improved community medical care and augmented health services in rural hospitals could mitigate barriers to health care access in indigenous, marginalised populations.

Residence in urban or rural counties in relation to opioid overdose mortality among Kentucky hospitalizations before and during the COVID-19 pandemic.

BACKGROUND: At the beginning of the opioid overdose epidemic, overdose mortality rates were higher in urban than in rural areas. We examined the association between residence in an urban or rural county and subsequent opioid overdose mortality in Kentucky, a state highly impacted by the opioid epidemic, and whether this was modified by the COVID-19 pandemic. METHODS: We captured hospitalizations in Kentucky from 2016 to 2020, involving an opioid using ICD-10-CM codes T40.0-T40.4 and T40.6. Patient's county was classified as urban or rural based on the NCHS Urban-Rural Classification Scheme. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of opioid overdose mortality, adjusted for demographics, hospitalization severity, and zip code SES. We assessed effect modification by the COVID-19 pandemic. RESULTS: Overall, patients living in urban counties had 46% higher odds of opioid overdose death than patients residing in rural counties (adjusted OR=1.46; 95% CI=1.22, 1.74). Before the pandemic, patients in urban counties had 63% increased odds of opioid overdose death (adjusted OR=1.63; 95% CI=1.34, 1.97); however, during the COVID-19 pandemic, patients in urban and rural counties became more similar in regard to opioid overdose mortality (adjusted OR=0.72; 95% CI=0.45, 1.16; p-value for interaction =0.02). CONCLUSION: Before the pandemic, living in urban counties was associated with higher opioid overdose mortality among Kentucky hospitalizations; however, during the COVID-19 pandemic, opioid overdose mortality in rural areas increased, approaching rates in urban areas. COVID-19 posed social, economic, and healthcare challenges that may be contributing to worsening mortality trends affecting both urban and rural patients.

Exposure to natural vegetation in relation to mammographic density in a Massachusetts-based clinical cohort.

Inverse associations between natural vegetation exposure (i.e., greenness) and breast cancer risk have been reported; however, it remains unknown whether greenness affects breast tissue development or operates through other mechanisms (e.g., body mass index [BMI] or physical activity). We examined the association between greenness and mammographic density-a strong breast cancer risk factor-to determine whether greenness influences breast tissue composition independent of lifestyle factors. Methods: Women (n = 2,318) without a history of breast cancer underwent mammographic screening at Brigham and Women's Hospital in Boston, Massachusetts, from 2006 to 2014. Normalized Difference Vegetation Index (NDVI) satellite data at 1-km2 resolution were used to estimate greenness at participants' residential address 1, 3, and 5 years before mammogram. We used multivariable linear regression to estimate differences in log-transformed volumetric mammographic density measures and 95% confidence intervals (CIs) for each 0.1 unit increase in NDVI. Results: Five-year annual average NDVI was not associated with percent mammographic density in premenopausal (ß = -0.01; 95% CI = -0.03, 0.02; P = 0.58) and postmenopausal women (ß = -0.02; 95% CI = -0.04, 0.01; P = 0.18). Results were similar for 1-year and 3-year NDVI measures and in models including potential mediators of BMI and physical activity. There were also no associations between greenness and dense volume and nondense volume. Conclusions: Greenness exposures were not associated with mammographic density. Impact: Prior observations of a protective association between greenness and breast cancer may not be driven by differences in breast tissue composition, as measured by mammographic density, but rather other mechanisms.

Prevalence of unmasked and improperly masked behavior in indoor public areas during the COVID-19 pandemic: Analysis of a stratified random sample from Louisville, Kentucky.

Wearing a facial mask can limit COVID-19 transmission. Measurements of communities' mask use behavior have mostly relied on self-report. This study's objective was to devise a method to measure the prevalence of improper mask use and no mask use in indoor public areas without relying on self-report. A stratified random sample of retail trade stores (public areas) in Louisville, Kentucky, USA, was selected and targeted for observation by trained surveyors during December 14-20, 2020. The stratification allowed for investigating mask use behavior by city district, retail trade group, and public area size. The total number of visited public areas was 382 where mask use behavior of 2,080 visitors and 1,510 staff were observed. The average prevalence of mask use among observed visitors was 96%, while the average prevalence of proper use was 86%. In 48% of the public areas, at least one improperly masked visitor was observed and in 17% at least one unmasked visitor was observed. The average prevalence of proper mask use among staff was 87%, similar to the average among visitors. However, the percentage of public areas where at least one improperly masked staff was observed was 33. Significant disparities in mask use and its proper use were observed among both visitors and staff by public area size, retail trade type, and geographical area. Observing unmasked and improperly masked visitors was more common in small (less than 1500 square feet) public areas than larger ones, specifically in food and grocery stores as compared to other retail stores. Also, the majority of the observed unmasked persons were male and middle-aged.

Weather and COVID-19 Deaths During the Stay-at-Home Order in the United States.

OBJECTIVE: To estimate the association between weather and COVID-19 fatality rates during US stay-at-home orders. METHODS: With a county-level longitudinal design, this study analyzed COVID-19 deaths from public health departments' daily reports and considered exposure as the 18 to 22 day-period before death. Models included state-level social distancing measures, Census Bureau demographics, daily weather information, and daily air pollution. The primary measures included minimum and maximum daily temperature, precipitation, ozone concentration, PM2.5 concentrations, and U.V. light index. RESULTS: A 1 °F increase in the minimum temperature was associated with 1.9% (95% CI, 0.2% to 3.6%) increase in deaths 20 days later. An ozone concentration increase of 1 ppb (part per billion) decreased daily deaths by 2.0% (95% CI, 0.1% to 3.6%); ozone levels below 38 ppb negatively correlated with deaths. CONCLUSIONS: Increased mobility may drive the observed association of minimum daily temperature on COVID-19 deaths.

County-level demographic, social, economic, and lifestyle correlates of COVID-19 infection and death trajectories during the first wave of the pandemic in the United States.

BACKGROUND: The US COVID-19 epidemic impacted counties differently across space and time, though large-scale transmission dynamics are unclear. The study's objective was to group counties with similar trajectories of COVID-19 cases and deaths and identify county-level correlates of the distinct trajectory groups. METHODS: Daily COVID-19 cases and deaths were obtained from 3141 US counties from January through June 2020. Clusters of epidemic curve trajectories of COVID-19 cases and deaths per 100,000 people were identified with Proc Traj. We utilized polytomous logistic regression to estimate Odds Ratios for trajectory group membership in relation to county-level demographics, socioeconomic factors, school enrollment, employment and lifestyle data. RESULTS: Six COVID-19 case trajectory groups and five death trajectory groups were identified. Younger counties, counties with a greater proportion of females, Black and Hispanic populations, and greater employment in private sectors had higher odds of being in worse case and death trajectories. Percentage of counties enrolled in grades 1-8 was associated with earlier-start case trajectories. Counties with more educated adult populations had lower odds of being in worse case trajectories but were generally not associated with worse death trajectories. Counties with higher poverty rates, higher uninsured, and more living in non-family households had lower odds of being in worse case and death trajectories. Counties with higher smoking rates had higher odds of being in worse death trajectory counties. DISCUSSION: In the absence of clear guidelines and personal protection, smoking, racial and ethnic groups, younger populations, social, and economic factors were correlated with worse COVID-19 epidemics that may reflect population transmission dynamics during January-June 2020. After vaccination of high-risk individuals, communities with higher proportions of youth, communities of color, smokers, and workers in healthcare, service and goods industries can reduce viral spread by targeting vaccination programs to these populations and increasing access and education on non-pharmaceutical interventions.

Contribution of socioeconomic and environmental factors to geographic disparities in breast cancer risk in the Nurses' Health Study II.

BACKGROUND: Evidence of geographic disparities in breast cancer incidence within the U.S. and spatial analyses can provide insight into the potential contribution of environmental exposures or other geographically-varying factors to these disparities. METHODS: We applied generalized additive models (GAMs) to smooth geocoded residential coordinates while adjusting for covariates. Our analysis included 3,478 breast cancer cases among 24,519 control women from the Nurses' Health Study II (NHSII). We first examined associations with residential location during adolescence (high school address) or early adulthood (address in 1991). We then assessed the contribution from known individual-level risk factors, measures of socioeconomic status (SES), and occupational and environmental factors that vary spatially and have been linked to breast cancer. Secondary analyses by estrogen receptor (ER) and menopausal status were also conducted. RESULTS: We identified geographic patterns of breast cancer risk associated with location during adolescence, with increased risk apparent in Michigan, the Northwest, and the New York City area, that shifted to southern New England when addresses during early adulthood were analyzed. Similar results were observed after adjustment for individual- and area-level factors, although spatial associations were no longer statistically significant. CONCLUSION: Breast cancer risk is not spatially uniform across the U.S. and incidence patterns varied depending on the timing during life of the residence considered. Geographic disparities persisted even after accounting for established and suspected breast cancer risk factors, suggesting that unmeasured environmental or lifestyle risk factors may explain geographic variation in risk in different parts of the country.

Involvement of fine particulate matter exposure with gene expression pathways in breast tumor and adjacent-normal breast tissue.

BACKGROUND: Fine particulate matter (PM2.5) has been associated with breast cancer specific mortality, particularly for women with Stage I cancer. We examined the biological pathways that are perturbed by PM2.5 exposures by analyzing gene expression measurements from breast tissue specimens. METHODS: The Nurses' Health Studies (NHS and NHSII) are prospective cohorts with archival breast tissue specimens from breast cancer cases. Global gene expression data were ascertained with the Affymetrix Glue Human Transcriptome Array 3.0. PM2.5 was estimated using spatio-temporal models linked to participants' home addresses. All analyses were performed separately in tumor (n = 591) and adjacent-normal (n = 497) samples, and stratified by estrogen receptor (ER) status and stage. We used multivariable linear regression, gene-set enrichment analyses (GSEA), and the least squares kernel machine (LSKM) to assess whether 3-year cumulative average pre-diagnosis PM2.5 exposure was associated with breast-tissue gene expression pathways among predominately Stage I and II women (90.7%) and postmenopausal (81.2%) women. Replication samples (tumor, n = 245; adjacent-normal, n = 165) were measured on Affymetrix Human Transcriptome Array (HTA 2.0). RESULTS: Overall, no pathways in the tumor area were significantly associated with PM2.5 exposure. Among 272 adjacent-normal samples from Stage I ER-positive women, PM2.5 was associated with perturbations in the oxidative phosphorylation, protein secretion, and mTORC1 signaling pathways (GSEA and LSKM p-values <0.05); however, results were not replicated in a small set of replication samples (n = 80). CONCLUSIONS: PM2.5 was generally not associated with breast tissue gene expression though was suggested to perturb oxidative phosphorylation and regulation of proteins and cellular signaling in adjacent-normal breast tissue. More research is needed on the biological role of PM2.5 that influences breast tumor progression.

Hepatitis A Outbreaks Associated With the Opioid Epidemic in Kentucky Counties, 2017-2018.

Objectives. To describe county-level socioeconomic profiles associated with Kentucky's 2017-2018 hepatitis A outbreak that predominately affected communities affected by the opioid epidemic.Methods. We linked county-level characteristics on socioeconomic and housing variables to counties' hepatitis A rates. Principal component analysis identified county profiles of poverty, education, disability, income inequality, grandparent responsibility, residential instability, and marital status. We used Poisson regression to estimate adjusted relative risks (RRs) and 95% confidence intervals (CIs).Results. Counties with scores reflecting an extremely disadvantaged profile (RR = 1.21; 95% CI = 0.99, 1.48) and greater percentage of nonmarried men, residential instability, and income inequality (RR = 1.15; 95% CI = 0.94, 1.41) had higher hepatitis A rates. Counties with scores reflecting more married adults, residential stability, and lower income inequality despite disability, poverty, and low education (RR = 0.77; 95% CI = 0.59, 1.00) had lower hepatitis A rates. Counties with a higher percentage of workers in the manufacturing industry had slightly lower rates (RR = 0.97; 95% CI = 0.94, 1.00).Conclusions. As expected, impoverished counties had higher hepatitis A rates. Evaluation across the socioeconomic patterns highlighted community-level factors (e.g., residential instability, income inequality, and social structures) that can be collected to augment hepatitis A data surveillance and used to identify higher-risk communities for targeted immunizations.

Low dose environmental radon exposure and breast tumor gene expression.

BACKGROUND: The International Agency for Research on Cancer classified radon and its decay-products as Group-1-human-carcinogens, and with the current knowledge they are linked specifically to lung cancer. Biokinetic models predict that radon could deliver a carcinogenic dose to breast tissue. Our previous work suggested that low-dose radon was associated with estrogen-receptor (ER)-negative breast cancer risk. However, there is limited research to examine the role of radon in breast cancer biology at the tissue level. We aim to understand molecular pathways linking radon exposure with breast cancer biology using transcriptome-wide-gene-expression from breast tumor and normal-adjacent tissues. METHODS: Our study included 943 women diagnosed with breast cancer from the Nurses' Health Study (NHS) and NHSII. We estimated cumulative radon concentration for each participant up-to the year of breast cancer diagnosis by linking residential addresses with a radon exposure model. Transcriptome-wide-gene-expression was measured with the Affymetrix-Glue-Human-Transcriptome-Array-3.0 and Human-Transcriptome-Array-2.0. We performed covariate-adjusted linear-regression for individual genes and further employed pathway-analysis. All analyses were conducted separately for tumor and normal-adjacent samples and by ER-status. RESULTS: No individual gene was associated with cumulative radon exposure in ER-positive tumor, ER-negative tumor, or ER-negative normal-adjacent tissues at FDR < 5%. In ER-positive normal-adjacent samples, PLCH2-reached transcriptome-wide-significance (FDR < 5%). Gene-set-enrichment-analyses identified 2-upregulated pathways (MAPK signaling and phosphocholine biosynthesis) enriched at FDR < 25% in ER-negative tumors and normal-adjacent tissues, and both pathways have been previously reported to play key roles in ionizing radiation induced tumorigenesis in experimental settings. CONCLUSION: Our findings provide insights into the molecular pathways of radon exposure that may influence breast cancer etiology.

Dioxin exposure and breast cancer risk in a prospective cohort study.

BACKGROUND: Dioxins are persistent organic pollutants generated from industrial combustion processes such as waste incineration. To date, results from epidemiologic studies of dioxin exposure and breast cancer risk have been mixed. OBJECTIVES: To prospectively examine the association between ambient dioxin exposure using a nationwide spatial database of industrial dioxin-emitting facilities and invasive breast cancer risk in the Nurses' Health Study II (NHSII). METHODS: NHSII includes female registered nurses in the US who have completed self-administered biennial questionnaires since 1989. Incident invasive breast cancer diagnoses were self-reported and confirmed by medical record review. Dioxin exposure was estimated based on residential proximity, duration of residence, and emissions from facilities located within 3, 5, and 10 km around geocoded residential addresses updated throughout follow-up. Cox regression models adjusted for breast cancer risk factors were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: From 1989 to 2013, 3840 invasive breast cancer cases occurred among 112,397 participants. There was no association between residential proximity to any dioxin facilities (all facilities combined) and breast cancer risk overall. However, women who resided within 10 km of any municipal solid waste incinerator (MSWI) compared to none had increased breast cancer risk (adjusted HR = 1.15, 95% CI: 1.03, 1.28), with stronger associations noted for women who lived within 5 km (adjusted HR = 1.25, 95% CI: 1.04, 1.52). Positive associations were also observed for longer duration of residence and higher dioxin emissions from MSWIs within 3, 5, and 10 km. There were no clear differences in patterns of association for ER + vs. ER-breast cancer or by menopausal status. DISCUSSION: Results from this study support positive associations between dioxin exposure from MSWIs and invasive breast cancer risk.

Prediagnostic 25-Hydroxyvitamin D Concentrations in Relation to Tumor Molecular Alterations and Risk of Breast Cancer Recurrence.

BACKGROUND: Although vitamin D inhibits breast tumor growth in experimental settings, the findings from population-based studies remain inconclusive. Our goals were to investigate the association between prediagnostic plasma 25-hydroxyvitamin D [25(OH)D] concentration and breast cancer recurrence in prospective epidemiologic studies and to explore the molecular underpinnings linking 25(OH)D to slower progression of breast cancer in the Nurses' Health Studies (NHS, N = 659). METHODS: Plasma 25(OH)D was measured with a high-affinity protein-binding assay and a radioimmunoassay. We profiled transcriptome-wide gene expression in breast tumors using microarrays. Hazard ratios (HR) of breast cancer recurrence were estimated from covariate-adjusted Cox regressions. We examined differential gene expression in association with 25(OH)D and employed pathway analysis. We derived a gene expression score for 25(OH)D, and assessed associations between the score and cancer recurrence. RESULTS: Although 25(OH)D was not associated with breast cancer recurrence overall [HR = 0.97; 95% confidence interval (CI), 0.88-1.08], the association varied by estrogen-receptor (ER) status (P interaction = 0.005). Importantly, among ER-positive stage I to III cancers, every 5 ng/mL increase in 25(OH)D was associated with a 13% lower risk of recurrence (HR = 0.87; 95% CI, 0.76-0.99). A null association was observed for ER-negative cancers (HR = 1.07; 95% CI, 0.91-1.27). Pathway analysis identified multiple gene sets that were significantly (FDR < 5%) downregulated in ER-positive tumors of women with high 25(OH)D (≥30 ng/mL), compared with those with low levels (<30 ng/mL). These gene sets are primarily involved in tumor proliferation, migration, and inflammation. 25(OH)D score derived from these gene sets was marginally associated with reduced risk of recurrence in ER-positive diseases (HR = 0.77; 95% CI, 0.59-1.01) in the NHS studies; however no association was noted in METABRIC, suggesting that further refinement is need to improve the generalizability of the score. CONCLUSIONS: Our findings support an intriguing line of research for studies to better understand the mechanisms underlying the role of vitamin D in breast tumor progression, particularly for the ER-positive subtype. IMPACT: Vitamin D may present a personal-level secondary-prevention strategy for ER-positive breast cancer.

Ultraviolet radiation exposure and breast cancer risk in the Nurses' Health Study II.

BACKGROUND: Ultraviolet (UV) radiation exposure, the primary source of vitamin D for most people, may reduce breast cancer risk. To date, epidemiologic studies have shown inconsistent results. METHODS: The Nurses' Health Study II is a U.S. nationwide prospective cohort of female registered nurses. A UV exposure model was linked with geocoded residential address histories. Early-life UV exposure was estimated based on the state of residence at birth, age 15, and age 30. Self-reported breast cancer was confirmed from medical records. Time-varying Cox regression models adjusted for established breast cancer risk factors were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: From 1989 to 2013, 3,959 invasive breast cancer cases occurred among 112,447 participants. Higher UV exposure during adulthood was not associated with invasive breast cancer risk overall (adjusted HR comparing highest to lowest quintile = 1.00, 95% CI: 0.90, 1.11, p for trend = 0.64) or according to estrogen receptor (ER) status. There were suggestive inverse associations between ER- breast cancer and early-life UV exposure at birth (adjusted HR = 0.94, 95% CI: 0.88, 1.01 per interquartile range increase [15.7 mW/m2]), age 15 (adjusted HR = 0.96, 95% CI: 0.89, 1.04 per 18.0 mW/m2), and age 30 (adjusted HR = 0.90, 95% CI: 0.82, 1.00 per 27.7 mW/m2). CONCLUSIONS: Ambient UV exposure during adulthood was not associated with risk of invasive breast cancer overall or by ER status. However, we observed suggestive inverse associations between early-life UV exposure and ER- breast cancer risk.

Particulate Matter and Traffic-Related Exposures in Relation to Breast Cancer Survival.

BACKGROUND: Although particulate matter (PM) has not been consistently associated with breast cancer risk, two studies have reported harmful associations for breast cancer survival. We examined PM exposures and breast cancer survival in two U.S.-based prospective cohort studies. METHODS: The Nurses' Health Study (NHS) and NHSII are cohorts with detailed data on medical history, lifestyle factors, and causes of death. Women with Stage I-III breast cancer (n = 8,936) were followed through June 2014. Residential PM was estimated using spatio-temporal models. We performed Cox regression to estimate hazard ratios (HR) of breast cancer-specific mortality and all-cause mortality for 10 µg/m3 increases in post-diagnosis PM. RESULTS: There were 1,211 breast cancer-specific deaths. Overall, PM was not associated with breast cancer-specific mortality [PM2.5: HR, 1.09; 95% confidence interval (CI), 0.87-1.36; PM2.5-10: HR, 1.03; 95% CI, 0.85-1.24; PM10: HR, 1.05; 95% CI, 0.89-1.24], but was associated with modest increases in all-cause mortality (PM2.5: HR, 1.12; 95% CI, 0.96-1.30; PM2.5-10: HR, 1.12; 95% CI, 1.00-1.24; PM10: HR, 1.09; 95% CI, 1.01-1.18). However, among participants with Stage I disease, PM2.5 was associated with higher breast cancer-specific mortality (HR, 1.64; 95% CI, 1.11-2.43). CONCLUSIONS: PM was not associated with breast cancer-specific death overall; however, higher PM was associated with all-cause mortality. Higher PM2.5 was associated with higher breast cancer-specific mortality among patients with Stage I breast cancer even after adjustment. IMPACT: Studies on ambient PM and breast cancer survival demonstrate that PM2.5 may have broader health effects than previously recognized and warrants further research on breast tumor progression.

Molecular mechanisms linking high body mass index to breast cancer etiology in post-menopausal breast tumor and tumor-adjacent tissues.

PURPOSE: In post-menopausal women, high body mass index (BMI) is an established breast cancer risk factor and is associated with worse breast cancer prognosis. We assessed the associations between BMI and gene expression of both breast tumor and adjacent tissue in estrogen receptor-positive (ER+) and estrogen receptor-negative (ER-) diseases to help elucidate the mechanisms linking obesity with breast cancer biology in 519 post-menopausal women from the Nurses' Health Study (NHS) and NHSII. METHODS: Differential gene expression was analyzed separately in ER+ and ER- disease both comparing overweight (BMI ≥ 25 to < 30) or obese (BMI ≥ 30) women to women with normal BMI (BMI < 25), and per 5 kg/m2 increase in BMI. Analyses controlled for age and year of diagnosis, physical activity, alcohol consumption, and hormone therapy use. Gene set enrichment analyses were performed and validated among a subset of post-menopausal cases in The Cancer Genome Atlas (for tumor) and Polish Breast Cancer Study (for tumor-adjacent). RESULTS: No gene was differentially expressed by BMI (FDR < 0.05). BMI was significantly associated with increased cellular proliferation pathways, particularly in ER+ tumors, and increased inflammation pathways in ER- tumor and ER- tumor-adjacent tissues (FDR < 0.05). High BMI was associated with upregulation of genes involved in epithelial-mesenchymal transition in ER+ tumor-adjacent tissues. CONCLUSIONS: This study provides insights into molecular mechanisms of BMI influencing post-menopausal breast cancer biology. Tumor and tumor-adjacent tissues provide independent information about potential mechanisms.

Corpora amylacea in prostatectomy tissue and associations with molecular, histological, and lifestyle factors.

BACKGROUND: Corpora amylacea are amyloid bodies commonly found adjacent to damaged prostate epithelium. Little is known about their formation or function. The current study sought to characterize corpora amylacea in prostate tissue and to describe their relationship with clinical, histological, molecular, and lifestyle factors, especially with chronic inflammation which is associated with aggressive disease. METHODS: We studied a cohort of 355 men with prostate cancer and tissue specimens from the Health Professionals Follow-Up Study. Pathologists examined H&E slides and undertook a standardized review for histologic data and inflammation. Trained observers counted corpora amylacea within the benign and predominately tumor areas. Immunohistochemistry biomarkers were available from tissue microarrays. We used multivariable logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) to assess associations of chronic inflammation, clinical, histological, molecular, and lifestyle factors with the presence of corpora amylacea. RESULTS: Corpora amylacea were present in benign tissue area for 298 men (84%). Specimens with moderate-to-severe chronic inflammation were more likely to have corpora amylacea in benign regions (OR = 5.4 95%CI 1.9, 15.6). Moreover, corpora amylacea were more common in men with higher body mass index (OR = 1.13 95%CI 1.01, 1.26). In contrast, Gleason grade (OR = 0.4 95%CI 0.2, 0.8), proliferation index (OR = 0.6 95%CI 0.3, 1.2) and the presence of the TMPRSS2:ERG fusion (OR = 0.4 95%CI 0.2, 0.8) were inversely associated with corpora amylacea presence. TURP specimens were less likely to have corpora amylacea than prostatectomy specimens (OR = 0.12 95%CI 0.03, 0.47). Age, PSA, stage, biomarkers of angiogenesis and PTEN, and vasectomy were not significantly associated with corpora amylacea. CONCLUSION: Corpora amylacea were common among men with prostate cancer and were associated with pro-inflammatory factors, some markers of less aggressive disease, and lack of the TMPRSS2:ERG fusion.