Are National Breast and Cervical Cancer Early Detection Program Recipients Providing Services in Counties Heavily Burdened by Breast and Cervical Cancer?

INTRODUCTION: Alignment of National Breast and Cervical Cancer Early Detection Program (NBCCEDP) clinical services with the spatial distribution of breast and cervical cancer burden is essential to maximizing programmatic impact and addressing cancer disparities. This study identified spatial clustering of breast and cervical cancer burden scores and assessed whether and to what extent NBCCEDP clinical services were associated with clusters for the 5-year period, 2015-2019. METHODS: We examined burden scores for spatial clustering using Local Indicators of Spatial Association (LISA) tests in GeoDA. We then used t-tests to compare the NBCCEDP 5-year average percentage of eligible women served clinical breast and cervical cancer services between hotspot (high burden) and coolspot clusters. RESULTS: There was statistically significant spatial clustering in the pattern of breast and cervical cancer burden scores across counties, with hotspot clusters mostly observed in the Southern region, Idaho and Nevada. For both breast and cervical cancer, higher percentages of eligible women received breast and cervical cancer clinical services in coolspot clusters compared to hotspot clusters during each year from 2015-2019. CONCLUSION: NBCCEDP clinical services can help reduce breast and cervical cancer burden. Yet, during 2015-2019, increased service delivery was not aligned with the spatial distribution of counties with greater breast and cervical cancer burdens. NBCCEDP recipients may improve their impact on breast and cervical cancer burden by prioritizing and consistently increasing service delivery in cancer burden hotspot clusters if they have not already maximized their resources in these areas.

Acceptability of Primary Care Counseling and Brief Educational Messages to Increase Awareness about Alcohol and Breast Cancer Risks among Bisexual and Lesbian Women.

This research had two aims: (1) to assess how often bisexual and lesbian women self-report screening and counseling for alcohol use in primary care settings; and (2) understand how bisexual and lesbian women respond to brief messages that alcohol increases breast cancer risk. The study sample consisted of 4891 adult U.S. women who responded to an online, cross-sectional Qualtrics survey in September-October 2021. The survey included the Alcohol Use Disorders Identification Test (AUDIT), questions about alcohol screening and brief counseling in primary care, and questions assessing awareness of the link between alcohol use and breast cancer. Bivariate analyses and logistic regression were conducted. Bisexual and lesbian women had higher odds of harmful drinking (AUDIT score ≥ 8) than heterosexual women (adjusted odds ratio [AOR] = 1.26, 95% confidence interval [CI] = 1.01-1.57 for bisexual women; AOR =1.78, 95% CI = 1.24-2.57 for lesbian women). However, bisexual and lesbian women were no more likely than heterosexual women to be advised about drinking in primary care. In addition, bisexual, lesbian, and heterosexual women had similar reactions to messages highlighting that alcohol is a risk factor for breast cancer. Women across all three sexual orientations who are harmful drinkers more often agreed to search for more information online or talk to a medical professional compared to non-harmful drinkers.

Cross-sectional study evaluating the association of haemophilia-related distress and clinically relevant outcomes.

INTRODUCTION: In chronic diseases, disease-related distress can impact disease outcomes. Distress and haemophilia-related distress has been demonstrated in people with haemophilia (PwH). The association of haemophilia-related distress on disease outcomes among PwH is unknown. AIM: To study the association of haemophilia-related distress with haemophilia specific outcomes, including adherence to prophylactic therapy, the presence of a target joint, healthcare utilization and work-impairment. METHODS: In a cross-sectional study, adults with haemophilia A or B were enrolled in a study to validate the haemophilia-related distress questionnaire (HRDq). In this planned analysis, univariate and multivariate associations between the HRDq total score and disease outcomes were explored. RESULTS: The 114 participants in this analysis were male, mostly with haemophilia A (92%) and severe disease (52%) with a median age of 31.9 years. On univariate analysis, HRDq total score (5-point change) was associated with the presence of a target joint (P = .002), high healthcare utilization (P = .011), poor adherence (P = .033) and work-impairment (P ≤ .001). After adjustment for age, race, severity and other potential confounders, adherence (aß 0.33, 95% CI .17, .49) and work-impairment (aß 4.69, 95% CI 3.27-6.1) remained statistically significantly associated with HRDq total score. CONCLUSION: Haemophilia-related distress is associated with poor adherence to factor prophylaxis and work-impairment. The direction of the association (causation) is yet to be determined and requires future study.

The Relationship between Health Literacy and COVID-19 Vaccination Prevalence during a Rapidly Evolving Pandemic and Infodemic.

The gap between how health information is communicated and what people understand and can use to make informed health decisions is called health literacy. This gap was exacerbated by the rapidly changing and excessive volume of information, misinformation, and disinformation during the COVID-19 pandemic. People with lower health literacy may not have understood the importance of COVID-19 vaccination for themselves or for their communities. Our aim was to understand health literacy levels within Fulton County, Georgia, and their relationship to vaccine prevalence. Fulton county residents ages 18 and over (n = 425) completed an on-line Health Literacy Questionnaire. Individual, organizational, functional, interactive, and critical health literacy scales were created. Vaccination prevalence data were collected from the Georgia Vaccine Distribution Dashboard. All data were divided into one of three county areas. There were statistically significant variations in vaccine prevalence χ2(3) = 29.325, p < 0.001 among the three county areas. All levels of health literacy predicted overall county vaccination prevalence F (4,420) = 85.941, p < 0.001, There were significant differences in health literacy levels among two of the three county area pairs; the lowest resourced county area had the lowest vaccination prevalence and health literacy rates. This is the first example of relating direct health literacy measures across a major metropolitan US county with vaccine prevalence data.

Geographic Examination of COVID-19 Test Percent Positivity and Proportional Change in Cancer Screening Volume, National Breast and Cervical Cancer Early Detection Program.

INTRODUCTION: In 2020, the COVID-19 pandemic led to significant declines in cancer screening, including among women served by the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). This study examined the spatial association between state-based COVID-19 test percent positivity and proportional change in NBCCEDP screening volume. METHODS: Using the COVID-19 Diagnostic Laboratory Testing dataset, we calculated state-based monthly COVID-19 test percent positivity from July through December 2020 and categorized rates into low, medium, and high groups. We used data from 48 NBCCEDP state awardees to calculate the state-based monthly proportional change in screening volume and compared data for July-December 2020 with the previous 5-year average for those months. We categorized changes in screening volume into large decrease, medium decrease, and minimal change and created maps of the associations between variable subgroups by using bivariate mapping in QGIS. RESULTS: Bivariate relationships between COVID-19 test percent positivity and proportional change in cancer screening volume varied over time and geography. In 5 of 6 months, 4 states had high COVID-19 test percent positivity and minimal change in breast or cervical cancer screening volume; 2 states had high COVID-19 test percent positivity and minimal change in breast and cervical cancer screening volume. CONCLUSION: Some states maintained pre-COVID-19 screening volumes despite high COVID-19 test percent positivity. Follow-up research will be conducted to determine how these states differ from those with consistent decreases in screening volume and identify factors that may have contributed to differences. This information could be useful for planning to maximize NBCCEDP awardees' ability to maintain screening volume during future public health emergencies.

Comparing direct oral anticoagulants and vitamin K antagonist use in morbidly obese patients with venous thromboembolism: A single center retrospective cohort study.

Introduction: Limited data exists on the safety and efficacy of direct-acting oral anticoagulants (DOAC) use in morbidly obese patients with venous thromboembolism (VTE). Given the benefits of DOAC use over vitamin K antagonists (VKAs), in terms of monitoring requirements, and dietary and drug interactions, it is important to evaluate whether this is consistent in the higher risk for VTE recurrence morbidly obese group body mass index (BMI ≥ 40 kg/m2). Materials and methods: This retrospective, single-center cohort study included patients with a BMI of at least 40 kg/m2 who were admitted to Emory University Hospital from 1st January 2012 to 31st May 2020 with acute VTE, and subsequently initiated on anticoagulation treatment with either DOAC or VKA (warfarin). Univariate and bivariate analyses were used to evaluate differences in demographics by treatment type and BMI. Multivariate Cox proportional hazard regression was used to assess the risk of VTE recurrence by type of treatment among morbidly obese patient subgroup. Results: There were 247 (11.8%) morbidly obese (≥ 40 kg/m2) patients who were more likely than non-obese patients to be younger, female, and of non-white race. Thirty percent of the study population (n=74) had a BMI >50 kg/m2. T ime-to-event analysis confirmed that the hazard of experiencing a recurrent thrombosis was not statistically significantly different among morbidly obese patients treated with a DOAC compared with VKA (hazard ratio [HR]: 0.28, confidence interval [CI] 0.07-1.11, p = 0.07). Conclusions: This study aligns with previous literature and confirms that morbidly obese patients receiving DOAC or VKA have similar risks of recurrent VTE.

A Systematic Review and Meta-Analysis of Preoperative Frailty Instruments Derived From Electronic Health Data.

BACKGROUND: Frailty is a strong predictor of adverse outcomes in the perioperative period. Given the increasing availability of electronic medical data, we performed a systematic review and meta-analysis with primary objectives of describing available frailty instruments applied to electronic data and synthesizing their prognostic value. Our secondary objectives were to assess the construct validity of frailty instruments that have been applied to perioperative electronic data and the feasibility of electronic frailty assessment. METHODS: Following protocol registration, a peer-reviewed search strategy was applied to Medline, Excerpta Medica dataBASE (EMBASE), Cochrane databases, and the Comprehensive Index to Nursing and Allied Health literature from inception to December 31, 2019. All stages of the review were completed in duplicate. The primary outcome was mortality; secondary outcomes included nonhome discharge, health care costs, and length of stay. Effect estimates adjusted for baseline illness, sex, age, procedure, and urgency were of primary interest; unadjusted and adjusted estimates were pooled using random-effects models where appropriate or narratively synthesized. Risk of bias was assessed. RESULTS: Ninety studies were included; 83 contributed to the meta-analysis. Frailty was defined using 22 different instruments. In adjusted data, frailty identified from electronic data using any instrument was associated with a 3.57-fold increase in the odds of mortality (95% confidence interval [CI], 2.68-4.75), increased odds of institutional discharge (odds ratio [OR], 2.40; 95% CI, 1.99-2.89), and increased costs (ratio of means, 1.54; 95% CI, 1.46-1.63). Most instruments were not multidimensional, head-to-head comparisons were lacking, and no feasibility data were reported. CONCLUSIONS: Frailty status derived from electronic data provides prognostic value as it is associated with adverse outcomes, even after adjustment for typical risk factors. However, future research is required to evaluate multidimensional instruments and their head-to-head performance and to assess their feasibility and clinical impact.

Geospatial analysis of multiple cancers in individuals in the US, 2004-2014.

BACKGROUND: There is a projected rapid increase in cancer survivors in the US population, from 15.5 million in 2016 to 26.1 million by 2040. Improvements in treatment and detection have led to increased survival, however, there is now a risk of developing new cancers as a result of environment toxins, behavioral risk factors, genetic predisposition, and late-term effects of radiation and chemotherapeutic treatments. This study takes a geospatial approach to examining the place of occurrence of multiple cancers originating in the population of four screenable cancers-female breast, colorectal, prostate, and cervical cancers-among the US population. METHODS: During 2004-2014, 6,523,532 primary cancer patients with one of these four screenable cancers were examined, and subsequent primary cancers (multiple cancers of any type) were noted. Individual level analyses estimated the odds of diagnosis with multiple cancers controlling for age, sex, and race-ethnicity. Change in effects on odds of multiple cancer diagnoses with age, sex, and race-ethnicity were evaluated controlling separately for late-stage diagnosis of the primary cancer or each primary cancer diagnosis type. County-level spatial cluster analysis was employed to identify and visualize higher than average multiple cancer rates. RESULTS: Over half of the study population were female and almost 30% of the study population were diagnosed at late-stage for their first cancer. Multiple occurrences of all cancers increased during the time period for patients with initial breast or colorectal cancers. Among BC primary cancer cases, subsequent multiple cancers were mostly new breast cancers. By contrast, for CRC primary cancer cases, subsequent multiple cancers were about equally likely to be new CRC cases or other cancer types. Sex, age and race-ethnicity were all significantly associated with multiple cancers. In the model controlling for CRC as the primary type, the age and race-ethnicity effects were somewhat different than for all the other models. Thus, there was something distinctly different about the multiple cancer incidence among patients with CRC as their primary cancer as compared to patients with BC, CVC, or PC primaries. In subsequent analyses by county, there were distinct geospatial patterns in multiple cancer rates with most high-rate clusters occurring in the north- and mid-west US. CONCLUSIONS: There were distinct individual level and geospatial disparities in multiple cancer diagnoses for the study population of all primary breast, colorectal, cervical, or prostate cancer patients during the decade studied. It is importance to emphasize continued screening for cancer survivors and research on personal and environmental drivers of multiple primary cancers.

Predicted Heart Age Among Cancer Survivors - United States, 2013-2017.

Approximately 15.5 million cancer survivors were alive in the United States in 2016 with expected growth to 26.1 million by 2040 (1). Cancer survivors are living longer because of advances in early detection and treatment, but face psychosocial, cognitive, financial, and physical challenges (1,2). Physical challenges include cardiovascular complications, partly because cancer and cardiovascular disease (CVD) share some cumulative risk factors including tobacco use, physical inactivity, obesity, poor diet, hypertension, diabetes, and dyslipidemia (3). In addition, many cancer treatments damage the heart, and some cancer types increase risk for developing CVD (4). The recognition and management of heart disease in cancer survivors has given rise to the discipline of cardio-oncology, which focuses on the cardiovascular health of this population (5). CVD risk has been previously estimated using prediction models, and studies suggest that physician-patient communication using predicted heart age rather than predicted 10-year risk has led to a more accurate perception of excess heart age, encouraged actions to adopt a healthy lifestyle, and improved modifiable CVD risk factors (6,7). Using the nonlaboratory-based Framingham Risk Score (FRS) to estimate 10-year risk for developing CVD, predicted heart age is estimated from the 10-year risk of CVD (predicted by age, sex, diabetes status, smoking status, systolic blood pressure, hypertension treatment status, and body mass index); it is the age of an otherwise healthy person with the same predicted risk, with all other risk factors included in the prediction model at the normal level (systolic blood pressure of 125 mmHg, no hypertension treatment, body mass index of 22.5, nonsmoker, and nondiabetic) (6). Using data from the Behavioral Risk Factor Surveillance System (BRFSS), this study estimates predicted heart age, excess heart age (difference between predicted heart age and actual age), and racial/ethnic and sociodemographic disparities in predicted heart age among U.S. adult cancer survivors and noncancer participants aged 30-74 years using previously published methods (7). A total of 22,759 men and 46,294 women were cancer survivors with a mean age of 48.7 and 48.3 years, respectively. The predicted heart age and excess heart age among cancer survivors were 57.2 and 8.5 years, respectively, for men and 54.8 and 6.5 years, respectively, for women, and varied by age, race/ethnicity, education and income. The use of predicted heart age by physicians to encourage cancer survivors to improve modifiable risk factors and make heart healthy choices, such as tobacco cessation, regular physical activity, and a healthy diet to maintain a healthy weight, can engage survivors in informed cancer care planning after diagnosis.

Finding "Bright Spots": Using Multiple Measures to Examine Local-Area Racial Equity in Cancer Mortality Outcomes.

In this article, we present a variety of measures that quantify equity in cancer mortality outcomes, demonstrate how the measures perform with various cancer types, and identify counties, or "bright spots," that meet the criteria of those measures. Using county-level age-adjusted mortality rates for 2007-2016 from the National Center for Health Statistics, we identified counties that had both equitable and optimal outcomes for Black and White death rates across 5 types of cancer: cancers of the lung/bronchus, prostate, female breast, colorectum, and liver. The number of counties that met the criteria ranged from 0 to 442, depending on cancer type and measure used. Prostate cancer and male liver cancer consistently had the lowest number of "bright spots," with a maximum of 3 counties meeting the most lenient criteria. This paper presents several ways to examine equity, using rate ratios and standard error measures, in cancer mortality outcomes. It highlights areas with positive progress toward equity and areas with a potential need for equity-focused cancer-control planning. Examining local areas of positive deviance can inform cancer-control programming and planning around health equity.

Observations of the global epidemiology of COVID-19 from the prepandemic period using web-based surveillance: a cross-sectional analysis.

Background Scant data are available about global patterns of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread and global epidemiology of early confirmed cases of COVID-19 outside mainland China. We describe the global spread of SARS-CoV-2 and characteristics of COVID-19 cases and clusters before the characterisation of COVID-19 as a pandemic. METHODS: Cases of COVID-19 reported between Dec 31, 2019, and March 10, 2020 (ie, the prepandemic period), were identified daily from official websites, press releases, press conference transcripts, and social media feeds of national ministries of health or other government agencies. Case characteristics, travel history, and exposures to other cases were abstracted. Countries with at least one case were classified as affected. Early cases were defined as those among the first 100 cases reported from each country. Later cases were defined as those after the first 100 cases. We analysed reported travel to affected countries among the first case reported from each country outside mainland China, demographic and exposure characteristics among cases with age or sex information, and cluster frequencies and sizes by transmission settings. FINDINGS: Among the first case reported from each of 99 affected countries outside of mainland China, 75 (76%) had recent travel to affected countries; 60 (61%) had travelled to China, Italy, or Iran. Among 1200 cases with age or sex information, 874 (73%) were early cases. Among 762 early cases with age information, the median age was 51 years (IQR 35-63); 25 (3%) of 762 early cases occurred in children younger than 18 years. Overall, 21 (2%) of 1200 cases were in health-care workers and none were in pregnant women. 101 clusters were identified, of which the most commonly identified transmission setting was households (76 [75%]; mean 2·6 cases per cluster [range 2-7]), followed by non-health-care occupational settings (14 [14%]; mean 4·3 cases per cluster [2-14]), and community gatherings (11 [11%]; mean 14·2 cases per cluster [4-36]). INTERPRETATION: Cases with travel links to China, Italy, or Iran accounted for almost two-thirds of the first reported COVID-19 cases from affected countries. Among cases with age information available, most were among adults aged 18 years and older. Although there were many clusters of household transmission among early cases, clusters in occupational or community settings tended to be larger, supporting a possible role for physical distancing to slow the progression of SARS-CoV-2 spread. FUNDING: None.

Visualizing Cancer Incidence and Mortality Estimates by Congressional Districts, United States 2012-2016.

BACKGROUND: Cancer incidence and death rates in the United States are often published at the county or statelevels; examining cancer statistics at the congressional district (CD) level allows decision makers to better understand how cancer is impacting the specific populations they represent. METHODS: Cancer incidence data were obtained from the Centers for Disease Control and Prevention's National Program of Cancer Registries and the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Mortality data were obtained from the National Center for Health Statistics. CD rates were estimated by assigning the county-level age-adjusted rates to the census block and weighting those by the block population proportion of the CD. Those weighted rates were then aggregated over the blocks within the CD to estimate the district rate. Incidence rate estimates for 406 CDs and death rate estimates for 436 CDs were reported according to the boundaries for the 115th Congress of the United States. Maps showing rate estimates for all cancers combined, lung/bronchus, colorectal, female breast, cervical, and prostate cancer are presented by sex and race/ethnicity. RESULTS: The distribution of cancer incidence and death rates by CDs show similar patterns to those that have been observed at the county and state levels, with the highest cancer incidence and death rates observed in CDs in the South and Eastern regions. CONCLUSION: This examination of cancer rates at the CD-level provides data that can be used to inform cancer control strategies at the local and national levels. Displaying the data with the Data Visualizations tool makes it easily accessible to the public and decision makers.

Correlates of colorectal cancer screening rates in primary care clinics serving low income, medically underserved populations.

INTRODUCTION: Screening for colorectal cancer (CRC) is effective in reducing CRC burden. Primary care clinics have an important role in increasing screening. We investigated associations between clinic-level CRC screening rates of the clinics serving low income, medically underserved population, and clinic-level screening interventions, clinic characteristics and community contexts. METHODS: Using data (2015-16) from the Centers for Disease Control and Prevention's (CDC) Colorectal Cancer Control Program, we linked clinic-level data with county-level contextual data from external sources. Analysis variables included clinic-level CRC screening rates, four different evidence-based interventions (EBIs) intended to increase screening, clinic characteristics, and clinic contexts. In the analysis (2018), we used weighted ordinary least square multiple regression analyses to associate EBIs and other covariates with clinic-level screening rates. RESULTS: Clinics (N = 581) had an average screening rate of 36.3% (weighted. Client reminders had the highest association (5.6 percentage points) with screening rates followed by reducing structural barriers (4.9 percentage points), provider assessment and feedback (3.2 percentage points), and provider reminders (<1 percentage point). Increases in the number of EBIs was associated with steady increases in the screening rate (5.4 percentage points greater for one EBI). Screening rates were 16.4 percentage points higher in clinics with 4 EBIs vs. no EBI. Clinic characteristics, contexts (e.g. physician density), and context-EBI interactions were also associated with clinic screening rates. CONCLUSIONS: These results may help clinics, especially those serving low income, medically underserved populations, select individual or combinations of EBIs suitable to their contexts while considering costs.

Update on triple-negative breast cancer disparities for the United States: A population-based study from the United States Cancer Statistics database, 2010 through 2014.

BACKGROUND: Triple-negative breast cancer (TNBC) has been associated with a more aggressive histology, poorer prognosis, and nonresponsiveness to hormone therapy. It is imperative that cancer research identify factors that drive disparities and focus on prevention. METHODS: Using the United States Cancer Statistics database, the authors examined differences between TNBCs compared with all other breast cancers with regard to age, race/ethnicity, and stage at diagnosis. RESULTS: A total of 1,151,724 cases of breast cancer were identified from 2010 through 2014, with the triple-negative phenotype accounting for approximately 8.4% of all cases. In unadjusted analyses, non-Hispanic black women (odds ratio [OR], 2.27; 95% CI, 2.23-2.31) and Hispanic women (OR, 1.22; 95% CI, 1.19-1.25) had higher odds of diagnosis when compared with non-Hispanic white women. Women aged <40 years had the highest odds of diagnosis compared with women aged 50 to 64 years (OR, 1.95; 95% CI, 1.90-2.01). Diagnosis at American Joint Committee on Cancer stage III and beyond conferred higher odds of the diagnosis of TNBC (OR for stage III, 1.69 [95% CI, 1.68-1.72]; and OR for stage IV, 1.47 [95% CI, 1.43-1.51]). Results varied slightly in adjusted analyses. CONCLUSIONS: The results of the current study demonstrated that there is a significant burden of disease in TNBC diagnosed among women of color, specifically non-Hispanic black women, and younger women. Additional studies are needed to determine drivers of disparities between race, age, and stage of disease at diagnosis.

Using Population Health Measures to Evaluate the Environmental Burden of Cancer at the County Level.

INTRODUCTION: Burden of disease is often defined by using epidemiologic measures. However, there may be latent aspects of disease burden that are not factored into these types of estimates. This study quantified environmental burden of disease by using population health indicators and exploratory factor analysis at the county level across the United States. METHODS: Ninety-nine variables drawn from public use data sets from 2010 to 2016 were used to create a multifactor index - the burden index. We applied principal components analysis with promax rotation to allow the factors to correlate. Correlation coefficients for each factor and the outcome of interest, age-adjusted cancer death rate, were calculated. We used both unadjusted and adjusted linear regression techniques. RESULTS: The final additive county-level index included 9 factors that explained 68.3% of the variance in the counties and county equivalents. The burden index had a moderate association with the age-adjusted cancer death rates (r =.48, P <.001), and adjusted linear regression with all 9 factors explained 34% of the variance in the age-adjusted cancer death rate. Results were mapped, and the geographic distribution of both the burden index and age-adjusted cancer mortality were assessed. There are distinct geospatial patterns for both. CONCLUSIONS: Results from this study show potential areas of need, as well as the importance of including environmental variables in the study of cancer etiology. Future studies can aim to validate these findings by quantifying burden as it relates to overall cancer mortality by using epidemiologic measures, along with other confirmatory statistical methods.

Modeling Geospatial Patterns of Late-Stage Diagnosis of Breast Cancer in the US.

In the US, about one-third of new breast cancers (BCs) are diagnosed at a late stage, where morbidity and mortality burdens are higher. Health outcomes research has focused on the contribution of measures of social support, particularly the residential isolation or segregation index, on propensity to utilize mammography and rates of late-stage diagnoses. Although inconsistent, studies have used various approaches and shown that residential segregation may play an important role in cancer morbidities and mortality. Some have focused on any individuals living in residentially segregated places (place-centered), while others have focused on persons of specific races or ethnicities living in places with high segregation of their own race or ethnicity (person-centered). This paper compares and contrasts these two approaches in the study of predictors of late-stage BC diagnoses in a cross-national study. We use 100% of U.S. Cancer Statistics (USCS) Registry data pooled together from 40 states to identify late-stage diagnoses among ~1 million new BC cases diagnosed during 2004-2009. We estimate a multilevel model with person-, county-, and state-level predictors and a random intercept specification to help ensure robust effect estimates. Person-level variables in both models suggest that non-White races or ethnicities have higher odds of late-stage diagnosis, and the odds of late-stage diagnosis decline with age, being highest among the

Geospatial Analysis of Inflammatory Breast Cancer and Associated Community Characteristics in the United States.

Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer, almost always diagnosed at late stage where mortality outcomes and morbidity burdens are known to be worse. Missed by mammography screening, IBC progresses rapidly and reaches late stage by the time of diagnosis. With an unknown etiology and poor prognosis, it is crucial to evaluate the distribution of the disease in the population as well as identify area social and economic contextual risk factors that may be contributing to the observed patterns of IBC incidence. In this study, we identified spatial clustering of county-based IBC rates among US females and examined the underlying community characteristics associated with the clusters. IBC accounted for ~1.25% of all primary breast cancers diagnoses in 2004-2012 and was defined by the Collaborative Stage (CS) Extension code 710 and 730. Global and local spatial clusters of IBC rates were identified and mapped. The Mann-Whitney U test was used to compare median differences in key contextual variables between areas with high and low spatial clusters of IBC rates. High clusters are counties and their neighbors that all exhibit above average rates, clustered together in a fashion that would be extremely unlikely to be observed by chance, and conversely for low clusters. There was statistically significant evidence of spatial clustering into high and low rate clusters. The average rate in the high rate clusters (n = 46) was approximately 12 times the average rate in low rate clusters (n = 126), and 2.2 times the national average across all counties. Significant differences were found in the medians of the underlying race, poverty, and urbanicity variables when comparing the low cluster counties with the high cluster counties (p < 0.05). Cluster analysis confirms that IBC rates differ geographically and may be influenced by social and economic environmental factors. Particular attention may need to be paid to race, urbanicity and poverty when considering risk factors for IBC and when developing interventions and alternative prevention strategies.

Using residential segregation to predict colorectal cancer stage at diagnosis: two different approaches.

PURPOSE: Studies have found a variety of evidence regarding the association between residential segregation measures and health outcomes in the United States. Some have focused on any individuals living in residentially segregated places, whereas others have examined whether persons of specific races or ethnicities living in places with high segregation of their own race or ethnicity have differential outcomes. This article compares and contrasts these two approaches in the study of predictors of late-stage colorectal cancer (CRC) diagnoses in a cross-national study. We argue that it is very important when interpreting results from studies like this to carefully consider the geographic scope of the analysis, which can significantly change the context and meaning of the results. METHODS: We use US Cancer Statistics Registry data from 40 states to identify late-stage diagnoses among over 500,000 CRC cases diagnosed during 2004-2009. We pool data over the states and estimate a multilevel model with person, county, and state levels and a random intercepts specification to ensure robust effect estimates. The isolation index of residential segregation is defined for racial and ethnic groups at the county level using Census 2000 data. The association between isolation indices and late-stage CRC diagnosis was measured by (1) anyone living in minority-segregated areas (place-centered approach) and by (2) individuals living in areas segregated by one's own racial or ethnic peers (person-centered approach). RESULTS: Findings from the place-centered approach suggest that living in a highly segregated African American community is associated with lower likelihood of late-stage CRC diagnosis, whereas the opposite is true for people living in highly segregated Asian communities, and living in highly segregated Hispanic communities has no significant association. Using the person-centered approach, we find that living in places segregated by one's racial or ethnic peers is associated with lower likelihood of late-stage CRC diagnosis. CONCLUSIONS: In a model that covers a large geographic area across the nation, the place-centered approach is most likely picking up geographic disparities that may be deepened by targeted interventions in minority communities. By contrast, the person-centered approach provides a national average estimate suggesting that residential isolation may confer community cohesion or support that is associated with better CRC prevention.

Aryl Hydrocarbon Receptor Ligand 5F 203 Induces Oxidative Stress That Triggers DNA Damage in Human Breast Cancer Cells.

Breast tumors often show profound sensitivity to exogenous oxidative stress. Investigational agent 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F 203) induces aryl hydrocarbon receptor (AhR)-mediated DNA damage in certain breast cancer cells. Since AhR agonists often elevate intracellular oxidative stress, we hypothesize that 5F 203 increases reactive oxygen species (ROS) to induce DNA damage, which thwarts breast cancer cell growth. We found that 5F 203 induced single-strand break formation. 5F 203 enhanced oxidative DNA damage that was specific to breast cancer cells sensitive to its cytotoxic actions, as it did not increase oxidative DNA damage or ROS formation in nontumorigenic MCF-10A breast epithelial cells. In contrast, AhR agonist and procarcinogen benzo[a]pyrene and its metabolite, 1,6-benzo[a]pyrene quinone, induced oxidative DNA damage and ROS formation, respectively, in MCF-10A cells. In sensitive breast cancer cells, 5F 203 activated ROS-responsive kinases: c-Jun-N-terminal kinase (JNK) and p38 mitogen activated protein kinase (p38). AhR antagonists (alpha-naphthoflavone, CH223191) or antioxidants (N-acetyl-l-cysteine, EUK-134) attenuated 5F 203-mediated JNK and p38 activation, depending on the cell type. Pharmacological inhibition of AhR, JNK, or p38 attenuated 5F 203-mediated increases in intracellular ROS, apoptosis, and single-strand break formation. 5F 203 induced the expression of cytoglobin, an oxidative stress-responsive gene and a putative tumor suppressor, which was diminished with AhR, JNK, or p38 inhibition. Additionally, 5F 203-mediated increases in ROS production and cytoglobin were suppressed in AHR100 cells (AhR ligand-unresponsive MCF-7 breast cancer cells). Our data demonstrate 5F 203 induces ROS-mediated DNA damage at least in part via AhR, JNK, or p38 activation and modulates the expression of oxidative stress-responsive genes such as cytoglobin to confer its anticancer action.