Search

Background: Cancer survivors are at high risk for chronic health conditions and physical and cognitive limitations. However, few studies have explored these outcomes among Lesbian, Gay, Bisexual, Transgender, Queer, Plus (LGBTQ+) survivors., Methods: We used pooled, weighted Behavioral Risk Factor Surveillance System data from 23 states that completed two specific modules at least once from 2020 to 2022. We calculated age-adjusted prevalence for heart disease, asthma, chronic obstructive pulmonary disease, depressive disorders, myocardial infarction, kidney disease, stroke, diabetes, hearing disability, vision disability, cognitive limitations, and difficulty walking, dressing, and running errands in LGBTQ+, lesbian, gay, or bisexual, transgender or gender nonconforming (TGNC), and non-LGBTQ+ cancer survivors. Four multivariable logistic regression models controlling for different factors were run for each outcome., Results: Of 40,990 cancer survivors, 1,715 were LGBTQ+. LGBTQ+ survivors had significantly higher age-adjusted prevalence of all outcomes. The prevalence of all outcomes was the highest among TGNC survivors, except for depressive disorders and cognitive limitations. LGBTQ+ survivors had higher odds of reporting asthma [adjusted OR (aOR): 1.5; 95% confidence interval (CI), 1.2-1.9], depressive disorders (aOR: 1.9; 95% CI, 1.6-2.4), kidney disease (aOR: 1.5; 95% CI, 1.1-2.1), stroke (aOR: 1.7; 95% CI, 1.3-2.3), diabetes (aOR: 1.3; 95% CI, 1.0-1.6), vision disability (aOR: 1.6; 95% CI, 1.2-2.2), cognitive limitations (aOR: 2.3; 95% CI, 1.8-2.9), difficulty walking (aOR: 1.7; 95% CI, 1.3-2.0), dressing (aOR: 2.0; 95% CI, 1.5-2.7), and running errands (aOR: 1.6; 95% CI, 1.3-2.1). In TGNC models, TGNC cancer survivors had increased odds of most outcomes in comparison to cisgender survivors., Conclusions: LGBTQ+ cancer survivors have an elevated burden of all chronic health conditions, disabilities, and limitations assessed. TGNC cancer survivors experience even higher burden of the same outcomes., Impact: Findings highlight substantial disparities regarding the health of LGBTQ+ cancer survivors. See related In the Spotlight, p. 1395., (©2024 American Association for Cancer Research.)

Background: Vigorous physical activity has been associated with lower risk of fatal prostate cancer. However, mechanisms contributing to this relationship are not understood., Methods: We studied 117 men with prostate cancer in the University of North Carolina Cancer Survivorship Cohort (UNC CSC) who underwent radical prostatectomy, and 101 radiation-treated prostate cancer patients in FASTMAN. Structured questionnaires administered in UNC CSC assessed physical activity. In both studies, digital image analysis of H&E-stained tissues was applied to quantify Tumor Infiltrating Lymphocytes (TILs) in segmented regions. Nanostring gene expression profiling in UNC CSC and microarray in FASTMAN were performed on tumor tissue and a 50-gene signature utilized to predict immune cell types., Results: Vigorous recreational activity, reported by 34 (29.1%) UNC men, was inversely associated with TILs abundance. Tumors of men reporting any vigorous activity versus none showed lower gene expression-predicted abundance of Th, exhausted CD4 T cells and macrophages. T cell subsets, including Treg, Th, Tfh, exhausted CD4 T cells, and macrophages were associated with increased risk of biochemical recurrence, only among men with ERG-positive tumors., Conclusions: Vigorous activity was associated with lower prostate tumor inflammation and immune microenvironment differences. Macrophages and T cell subsets, including those with immunosuppressive roles and those with lower abundance in men reporting vigorous exercise, were associated with worse outcomes in ERG-positive prostate cancer., Impact: Our novel findings contribute to our understanding of the role of the tumor immune microenvironment in prostate cancer progression, and may provide insight into how vigorous exercise could affect prostate tumor biology.

Purpose: Smoking is a modifiable lifestyle factor that has not been established as a prostate cancer risk factor, nor emphasized in prostate cancer prevention. Studies have shown that African American (AA) smokers have a poorer cancer prognosis than European Americans (EAs), while having a lower prevalence of heavy smoking. We examined the relationship between cigarette smoking and prostate cancer aggressiveness and assessed racial differences in smoking habits on the probability of high-aggressive prostate cancer., Methods: Using data from the North Carolina-Louisiana Prostate Cancer Project (n = 1,279), prostate cancer aggressiveness was defined as high or low based on Gleason scores, serum prostate-specific antigen levels, and tumor stage. Cigarette smoking was categorized as current, former, or never smokers. Multivariable logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI)., Results: Self-reported current (OR = 1.99; 95% CI 1.30-3.06) smoking was associated with high-aggressive prostate cancer relative to never smokers. When stratified by self-reported race, the odds of having high-aggressive cancer increased among AA current (OR = 3.58; 95% CI 2.04-6.28) and former smokers (OR = 2.21; 95% CI 1.38-3.53) compared to AA never smokers, but the odds were diminished among the EA stratum (P self-reported race x smoking status  = 0.003)., Conclusion: Cigarette smoking is associated with prostate cancer aggressiveness, a relationship modulated by self-reported race. Future research is needed to investigate types of cigarettes smoked and metabolic differences that may be contributing to the racial disparities observed., (© 2024. The Author(s).)

Purpose: Genomic tests, such as the Oncotype Dx 21-gene and Prosigna risk of recurrence (ROR-P) assay, are commonly used for breast cancer prognostication. Emerging data suggest variability between assays, but this has not been compared in diverse populations., Materials and Methods: RNA sequencing was performed on 647 previously untreated stage I-III estrogen receptor-positive/human epidermal growth factor receptor 2-negative tumors in the Carolina Breast Cancer Study, which oversampled Black and younger women (age <50 years at diagnosis), using research versions of two common RNA-based prognostic assays: ROR-P R and the 21-gene recurrence score (RS R ). Relative frequency differences and 95% CIs were estimated for associations with race and age, and hazards of 5-year local or distant recurrence were modeled with Cox regression. Proliferation and estrogen module scores from each assay, representing broad activity of genes in those pathways, were examined to guide interpretation of differences between tests., Results: Among both younger and older individuals, Black women had higher frequency of intermediate and high ROR-P R scores than non-Black women. Race was not significantly associated with RS R in either age group. High (hazard ratio [HR], 4.67 [95% CI, 1.73 to 12.70]) and intermediate (HR, 2.12 [95% CI, 0.98 to 4.62]) ROR-P R scores were associated with greater risk of recurrence, but RS R did not predict recurrence. RS R emphasized estrogen over proliferation modules, whereas ROR-P R emphasized proliferation. Higher proliferation scores were associated with younger age and Black race in both assays. Modifications to the RS R algorithm that increased emphasis on proliferation improved prognostication in this diverse population., Conclusion: ROR-P R and the 21-gene RS R differentially emphasize estrogen-related and proliferative biology. The emphasis of 21-gene RS on estrogen-related biology and lower endocrine therapy initiation among Black women may contribute to poorer prognostic ability in heterogeneously treated populations.

African-ancestry (AA) participants are underrepresented in genetics research. Here, we conducted a transcriptome-wide association study (TWAS) in AA female participants to identify putative breast cancer susceptibility genes. We built genetic models to predict levels of gene expression, exon junction, and 3' UTR alternative polyadenylation using genomic and transcriptomic data generated in normal breast tissues from 150 AA participants and then used these models to perform association analyses using genomic data from 18,034 cases and 22,104 controls. At Bonferroni-corrected P < 0.05, we identified six genes associated with breast cancer risk, including four genes not previously reported (CTD-3080P12.3, EN1, LINC01956 and NUP210L). Most of these genes showed a stronger association with risk of estrogen-receptor (ER) negative or triple-negative than ER-positive breast cancer. We also replicated the associations with 29 genes reported in previous TWAS at P < 0.05 (one-sided), providing further support for an association of these genes with breast cancer risk. Our study sheds new light on the genetic basis of breast cancer and highlights the value of conducting research in AA populations., (© 2024. The Author(s).)

Purpose: Screening history influences stage at detection, but regular preventive care may also influence breast tumor diagnostic characteristics. Few studies have evaluated healthcare utilization (both screening and primary care) in racially diverse screening-eligible populations., Methods: This analysis included 2,058 women age 45-74 (49% Black) from the Carolina Breast Cancer Study, a population-based cohort of women diagnosed with invasive breast cancer between 2008 and 2013. Screening history (threshold 0.5 mammograms per year) and pre-diagnostic healthcare utilization (i.e. regular care, based on responses to "During the past ten years, who did you usually see when you were sick or needed advice about your health?") were assessed as binary exposures. The relationship between healthcare utilization and tumor characteristics were evaluated overall and race-stratified., Results: Among those lacking screening, Black participants had larger tumors (5 + cm) (frequency 19.6% vs 11.5%, relative frequency difference (RFD) = 8.1%, 95% CI 2.8-13.5), but race differences were attenuated among screening-adherent participants (10.2% vs 7.0%, RFD = 3.2%, 0.2-6.2). Similar trends were observed for tumor stage and mode of detection (mammogram vs lump). Among all participants, those lacking both screening and regular care had larger tumors (21% vs 8%, RR = 2.51, 1.76-3.56) and advanced (3B +) stage (19% vs 6%, RR = 3.15, 2.15-4.63) compared to the referent category (screening-adherent and regular care). Under-use of regular care and screening was more prevalent in socioeconomically disadvantaged areas of North Carolina., Conclusions: Access to regular care is an important safeguard for earlier detection. Our data suggest that health equity interventions should prioritize both primary care and screening., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

We performed genome-wide association studies of breast cancer including 18,034 cases and 22,104 controls of African ancestry. Genetic variants at 12 loci were associated with breast cancer risk (P < 5 × 10 -8 ), including associations of a low-frequency missense variant rs61751053 in ARHGEF38 with overall breast cancer (odds ratio (OR) = 1.48) and a common variant rs76664032 at chromosome 2q14.2 with triple-negative breast cancer (TNBC) (OR = 1.30). Approximately 15.4% of cases with TNBC carried six risk alleles in three genome-wide association study-identified TNBC risk variants, with an OR of 4.21 (95% confidence interval = 2.66-7.03) compared with those carrying fewer than two risk alleles. A polygenic risk score (PRS) showed an area under the receiver operating characteristic curve of 0.60 for the prediction of breast cancer risk, which outperformed PRS derived using data from females of European ancestry. Our study markedly increases the population diversity in genetic studies for breast cancer and demonstrates the utility of PRS for risk prediction in females of African ancestry., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Clonal hematopoiesis of indeterminate potential (CHIP), the expansion of leukemogenic mutations in white blood cells, has been associated with increased risk of atherosclerotic cardiovascular diseases, cancer, and mortality., Objective: We examined the relationship between individual- and neighborhood-level socioeconomic status (SES) and CHIP and evaluated effect modification by interpersonal and intrapersonal resources., Methods: The study population included 10,799 postmenopausal women from the Women's Health Initiative without hematologic malignancy or antineoplastic medication use. Individual- and neighborhood (Census tract)-level SES were assessed across several domains including education, income, and occupation, and a neighborhood-level SES summary z-score, which captures multiple dimensions of SES, was generated. Interpersonal and intrapersonal resources were self-reports. CHIP was ascertained based on a prespecified list of leukemogenic driver mutations. Weighted logistic regression models adjusted for covariates were used to estimate risk of CHIP as an odds ratio (OR) and 95% confidence interval (95% CI)., Results: The interval-scale neighborhood-level SES summary z-score was associated with a 3% increased risk of CHIP: OR (95% CI) = 1.03 (1.00-1.05), p = .038. Optimism significantly modified that estimate, such that among women with low/medium and high levels of optimism, the corresponding ORs (95% CIs) were 1.03 (1.02-1.04) and 0.95 (0.94-0.96), p Interaction < .001., Conclusions: Our findings suggest that reduced risk of somatic mutation may represent a biological pathway by which optimism protects contextually advantaged but at-risk women against age-related chronic disease and highlight potential benefits of long-term, positive psychological interventions., (Published by Elsevier Inc.)

The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Prostate cancer (PCa) is a significant health burden in Sub-Saharan Africa, with mortality rates loosely linked to African ancestry. Yet studies aimed at identifying contributing risk factors are lacking within the continent and as such exclude for significant ancestral diversity. Here, we investigate a series of epidemiological demographic and lifestyle risk factors for 1387 men recruited as part of the multi-ethnic Southern African Prostate Cancer Study (SAPCS). We found poverty to be a decisive factor for disease grade and age at diagnosis, with other notably significant PCa associated risk factors including sexually transmitted diseases, erectile dysfunction, gynaecomastia, and vertex or complete pattern balding. Aligned with African American data, Black ethnicity showed significant risk for PCa diagnosis (OR = 1.44, 95% CI 1.05-2.00), and aggressive disease presentation (ISUP ≥ 4: OR = 2.25, 95% CI   1.49-3.40). New to this study, we demonstrate African ancestral population substructure associated PCa disparity, observing increased risk for advanced disease for the southern African Tsonga people (ISUP ≥ 4: OR = 3.43, 95% CI   1.62-7.27). Conversely, South African Coloured were less likely to be diagnosed with aggressive disease overall (ISUP ≥ 3: OR = 0.38, 95% 0.17-0.85). Understanding the basis for PCa health disparities calls for African inclusion, however, lack of available data has limited the power to begin discussions. Here, focusing on arguably the largest study of its kind for the African continent, we draw attention to the contribution of within African ancestral diversity as a contributing factor to PCa health disparities within the genetically diverse region of southern Africa., (© 2023. The Author(s).)

In this study we analyzed data collected from the onset of the COVID-19 pandemic through March 31, 2022, to identify temporal shifts in breast exam volume. Screening mammography volume stabilized toward the end of the study period, and diagnostic exam volume varied over time and by age. Older women experienced a decline in diagnostic exam volume between August 2020 and April 2021 that was not observed among women aged younger than 50 years (50-69 years: monthly percentage change [MPC] = -6.5%; and 70 years and older: MPC = -15.7%). With respect to breast biopsy volume, women aged younger than 70 years had increased exam volume beginning in April 2020 and June 2020, whereas a corresponding increase among older women was delayed until April 2021 (70 years and older: MPC = 9.3%). Findings from our study suggest a temporal shift in the use of breast exams that could result in differential detection of breast cancer by age., (© The Author(s) 2023. Published by Oxford University Press.)

Background: We examined associations between two forms of testosterone therapy (TT) and risks of seven cancers among men., Methods: SEER-Medicare combines cancer registry data from the Surveillance, Epidemiology, and End Results programme with Medicare claims. Our population-based case-control study included incident cancer cases diagnosed between 1992-2015: prostate (n = 130,713), lung (n = 105,466), colorectal (n = 56,433), bladder (n = 38,873), non-Hodgkin lymphoma (n = 17,854), melanoma (n = 14,241), and oesophageal (n = 9116). We selected 100,000 controls from a 5% random sample of Medicare beneficiaries and used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI)., Results: TT was associated with lower risk of distant-stage prostate cancer (injection/implantation OR = 0.72, 95% CI: 0.60-0.86; topical OR = 0.50, 95% CI: 0.24-1.03). We also observed inverse associations for distant-stage colorectal cancer (injection/implantation OR = 0.75, 95% CI: 0.62-0.90; topical OR = 0.11, 95% CI: 0.05-0.24). Risks of distant-stage colorectal and prostate cancers decreased with time after initiating TT by injection/implantation. By contrast, TT was positively associated with distant-stage melanoma (injection/implantation OR = 1.70, 95% CI: 1.37-2.11). TT was not associated with bladder cancer, oesophageal cancer, lung cancer or non-Hodgkin lymphoma., Conclusion: TT was inversely associated with distant-stage prostate and colorectal cancers but was positively associated with distant-stage melanoma. These observations may suggest an aetiologic role for TT or the presence of residual confounding., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Precision cancer prevention as it is currently envisioned is a targeted, molecular-based approach to intercept carcinogenesis before cancer develops or before it becomes untreatable. Unfortunately, due to systemic biases, current precision cancer prevention interventions might not be effective in all populations, especially in minoritized communities. In addition, not all cancer risk is attributable to genetic or even biological factors, but includes social determinants of health (SDH). Here, we propose a broader framework for precision cancer prevention, anchored in optimizing the benefits to harms for all people. We propose that precision cancer prevention considers not only what is being delivered, but also for whom, where, and how, with a goal of achieving cancer prevention health equity., Competing Interests: Declaration of interests None declared by the authors., (Published by Elsevier Inc.)

This study examines oncologist-reported reasons for not using multimarker tumor panel testing and the association between these reasons and oncologist-level, facility-level, and patient-mix characteristics., Methods: We used data collected from a nationally representative sample (N = 1,281) of medical oncologists participating in the National Cancer Institute's National Survey of Precision Medicine in Cancer Treatment ., Results: In addition to testing not being seen as relevant (87%) and no evidence of test utility (77%), the most frequently reported reasons for not ordering a multimarker tumor panel test was difficulty in obtaining sufficient tissue (57%) and using individual gene tests (72%). These reasons were more likely to be reported by oncologists practicing in rural clinics and less likely to be reported by oncologists with an academic affiliation or with access to genetic services such as on-site genetic counselors and internal genetic testing policies., Conclusion: Modifiable, organizational factors were associated with ordering multimarker tumor panels. Receipt of genomics training and organizational policies related to the use of genomics were associated with lower reporting of barriers to ordering multimarker tumor panels, pointing to potential targets for future studies aimed at increasing appropriate multimarker tumor panel testing in cancer treatment management., (© 2021 by American Society of Clinical Oncology.)

Background: In the USA, it is unknown whether metastatic prostate cancer incidence has continued to increase and whether racial differences have persisted., Objective: Combining multiple imputation with age and delay adjustment, we provide an up-to-date, comprehensive assessment of US prostate cancer incidence trends by stage and race., Design, Setting, and Participants: From Surveillance Epidemiology and End Results (SEER)-18, 774 240 prostate cancer cases were diagnosed during 2004-2017., Outcome Measurements and Statistical Analysis: Multiple imputation assigned prostate cancer stage to the 4.7% of cases with missing stage, which varied by year and race-ethnicity. SEER delay factors adjusted case counts to anticipated future data corrections. Twenty datasets were imputed, and Rubin's rules were used for summary estimation. Overall and stage-specific rates were estimated and stratified by race and age group. Joinpoint software identified significant temporal changes and estimated annual percentage changes. We compared these estimates without multiple imputation and delay adjustment., Results and Limitations: Metastatic prostate cancer incidence increased during 2011-2017, with an annual percentage change of 5.5. This was followed by increases in localized and regional disease since 2014. Non-Hispanic black men continued to have the highest incidence, especially for metastatic disease. The increasing rate of metastatic prostate cancer in non-Hispanic white men aged 50-74 yr accelerated recently, and the incidence was 56% higher in 2017 than in 2004. Rates without multiple imputation and delay adjustment were quantitatively and qualitatively different. This observational study is unable to assign causes to observed changes in prostate cancer incidence., Conclusions: Multiple imputation and delay adjustment are essential for portraying accurately stage- and race-specific prostate cancer incidence as clinical practice evolves., Patient Summary: In the USA, diagnosis of prostate cancer that has spread to distant sites (metastatic disease) continues to increase. Black men continue to have higher risks of being diagnosed with metastatic prostate cancer than other race-ethnicities., (Published by Elsevier B.V.)

Objective: Next generation sequencing (NGS) may aid in tumor classification and treatment. Barriers to shared decision-making may influence use of NGS. We examined, from oncologists' perspectives, whether barriers to involving patients/families in decision-making were associated with NGS use., Methods: Using data from the first national survey of medical oncologists' perspectives on precision medicine (N = 1281), we approached our analyses in two phases. Bivariate analyses initially evaluated associations between barriers to involving patients/families in deciding to use NGS and provider- and organizational-level characteristics. Modified Poisson regressions then examined associations between patient/family barriers and NGS use., Results: Approximately 59 % of oncologists reported at least one barrier to involving patients/families in decision-making regarding NGS use. Those reporting patient/family barriers tended to have fewer genomic resources at their practices, to be in rural or suburban areas, and to have a higher proportion of Medicaid patients. However, these barriers were not associated with NGS use., Conclusions: Oncologists encounter barriers to involving patients/families in NGS testing decisions. Organizational barriers may also potentially play a role in testing decisions., Practice Implications: To foster patient-centered care, strategies to support patient involvement in genomic testing decisions are needed, particularly among practices in low-resource settings., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Obesity has been associated with an increased risk of advanced prostate cancer. However, most studies have been conducted among North American and European populations. Prostate cancer mortality appears elevated in West Africa, yet risk factors for prostate cancer in this region are unknown. We thus examined the relationship between obesity and prostate cancer using a case-control study conducted in Accra, Ghana in 2004 to 2012. Cases and controls were drawn from a population-based sample of 1037 men screened for prostate cancer, yielding 73 cases and 964 controls. An additional 493 incident cases were recruited from the Korle-Bu Teaching Hospital. Anthropometric measurements were taken at enrollment. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR) and prostate cancer, adjusting for potential confounders. The mean BMI was 25.1 kg/m 2 for cases and 24.3 kg/m 2 for controls. After adjustment, men with BMI ≥ 30 kg/m 2 had an increased risk of prostate cancer relative to men with BMI < 25 kg/m 2 (OR 1.86, 95% CI 1.11-3.13). Elevated WC (OR 1.76, 95% CI 1.24-2.51) and WHR (OR 1.46, 95% CI 0.99-2.16) were also associated with prostate cancer. Associations were not modified by smoking status and were evident for low- and high-grade disease. These findings indicate that overall and abdominal obesity are positively associated with prostate cancer among men in Ghana, implicating obesity as a potentially modifiable risk factor for prostate cancer in this region., (© 2020 UICC.)

Purpose: Previous studies have shown an overall decreased risk of second cancers among prostate cancer survivors, but this has not been comprehensively examined by race/ethnicity. We conducted a retrospective cohort study of 716,319 one-year survivors of prostate cancer diagnosed at ages 35-84 during 2000-2015 as reported to 17 US Surveillance, Epidemiology and End Results (SEER) registries., Methods: We estimated standardized incidence ratios (SIRs) for second primary non-prostate malignancies by race/ethnicity (non-Latino white, Black, Asian/Pacific Islander [API] and Latino), by Gleason, and by time since prostate cancer diagnosis. Poisson regression models were used to test heterogeneity between groups with the expected number as the offset., Results: 60,707 second primary malignancies were observed. SIRs for all second cancers combined varied significantly by race/ethnicity: SIR white : 0.88 (95% confidence interval: 0.87-0.89), SIR Latino : 0.92 (0.89-0.95), SIR Black : 0.97 (0.95-0.99), and SIR API : 1.05 (1.01-1.09) (p-heterogeneity < 0.001). SIRs for all cancers combined were higher among survivors of higher vs. lower Gleason prostate cancers irrespective of race/ethnicity. We observed significant heterogeneity by race/ethnicity in SIRs for 9 of 14 second cancer types investigated including lung, bladder, kidney, and liver., Conclusions: Our results confirm that most prostate cancer survivors have lower risks of second cancers than expected, but the magnitude varied by race/ethnicity. Exceptionally, API men had small but significantly increased risk. Further research to understand drivers of the observed race/ethnicity heterogeneity is warranted.

Endorsing prototypes of cigarette smokers predicts cigarette smoking, but less is known about prototypes of users of other tobacco products. Our study sought to establish the reliability and validity of a measure of prototypes of smokers and e-cigarette users. Participants were from a national survey of smokers and non-smokers ( n = 1414), a randomized clinical trial (RCT) of adult smokers ( n = 2149), and adolescent children of adults in the trial ( n = 112). The Prototypes of Tobacco Users Scale (POTUS) has four positive adjectives (cool, sexy, smart, and healthy) and four negative adjectives (disgusting, unattractive, immature, and inconsiderate) describing cigarette smokers and e-cigarette users. Confirmatory factor analyses identified a two-factor solution. The POTUS demonstrated strong internal consistency reliability in all three samples (median α = 0.85) and good test-retest reliability among adults in the RCT (median r = 0.61, 1-4 weeks follow-up). In the RCT, smokers more often agreed with negative prototypes for smokers than for e-cigarette users (mean = 2.03 vs. 1.67, p < 0.05); negative prototypes at baseline were also associated with more forgoing of cigarettes and making a quit attempt at the end of the trial (Week 4 follow-up). The POTUS may be useful to public health researchers seeking to design interventions that reduce tobacco initiation or cessation through the manipulation of tobacco user prototypes.

Background: Differential uptake of prostate-specific antigen testing in the US and UK has been linked to between-country differences for prostate cancer incidence. We examined stage-specific fatal prostate cancer incidence trends in the US and England, by treatment and race/ethnicity., Methods: Using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program and Public Health England's National Cancer Registration and Analysis Service, we identified prostate cancer patients diagnosed between 1995 and 2005, aged 45-84 years. Fatal prostate cancer was defined as death attributed to the disease within 10 years of diagnosis. We used age-period-cohort models to assess trends in fatal prostate cancer incidence., Results: Fatal prostate cancer incidence declined in the US by -7.5% each year and increased in England by 7.7% annually. These trends were primarily driven by locoregional disease in the US and distant disease in England. Black men in both countries had twofold to threefold higher fatal prostate cancer incidence rates, when compared with their white counterparts; however, receipt of radical prostatectomy lessened this disparity., Conclusions: We report a significant increasing rate of fatal prostate cancer incidence among English men. The black-white racial disparity appears pervasive but is attenuated among those who received radical prostatectomy in the US.

RNA-based, multi-gene molecular assays are available and widely used for patients with ER-positive/HER2-negative breast cancers. However, RNA-based genomic tests can be costly and are not available in many countries. Methods for inferring molecular subtype from histologic images may identify patients most likely to benefit from further genomic testing. To identify patients who could benefit from molecular testing based on H&E stained histologic images, we developed an image analysis approach using deep learning. A training set of 571 breast tumors was used to create image-based classifiers for tumor grade, ER status, PAM50 intrinsic subtype, histologic subtype, and risk of recurrence score (ROR-PT). The resulting classifiers were applied to an independent test set ( n  = 288), and accuracy, sensitivity, and specificity of each was assessed on the test set. Histologic image analysis with deep learning distinguished low-intermediate vs. high tumor grade (82% accuracy), ER status (84% accuracy), Basal-like vs. non-Basal-like (77% accuracy), Ductal vs. Lobular (94% accuracy), and high vs. low-medium ROR-PT score (75% accuracy). Sampling considerations in the training set minimized bias in the test set. Incorrect classification of ER status was significantly more common for Luminal B tumors. These data provide proof of principle that molecular marker status, including a critical clinical biomarker (i.e., ER status), can be predicted with accuracy >75% based on H&E features. Image-based methods could be promising for identifying patients with a greater need for further genomic testing, or in place of classically scored variables typically accomplished using human-based scoring., Competing Interests: C.M.P. is an equity stock holder and Board of Directors member of BioClassifier, L.L.C. and C.M.P. has filed patents on the PAM50 subtyping assay. The other authors declare no competing interests.

Mutations in tumor suppressor TP53 have been inconsistently linked to breast cancer risk factors and survival. Immunohistochemistry (IHC) staining, a primary clinical means of TP53 mutation determination, only detects mutations that facilitate protein accumulation (e.g., missense mutations). RNA-based pathway methods capture functional status and may aid in understanding the role of TP53 function in racial disparities of breast cancer. TP53 status was assessed among invasive breast cancer cases from the Carolina Breast Cancer Study (CBCS) (2008-2013) using IHC and an established RNA-based TP53 signature (CBCS and The Cancer Genome Atlas (TCGA)). Frequency of TP53 status (IHC, RNA-based) was estimated in association with tumor characteristics, PAM50 intrinsic subtype, age, and race using relative frequency differences (RFDs) and 95% confidence intervals (95% CI) as the measure of association. Approximately 60% of basal-like tumors were TP53 protein positive (IHC), while nearly 100% were TP53 mutant-like (RNA). Luminal A tumors had low frequency of TP53 positivity (IHC: 7.9%) and mutant-like status (RNA: 1.7%). Mutant-like TP53 (RNA) was strongly associated with age ≤50 years, high tumor grade, advanced stage of disease, large tumor size, and basal-like and HER2 intrinsic subtypes. Black race was strongly associated with TP53 mutant-like status (RNA ) (RFD: 24.8%, 95% CI: 20.5, 29.0) even after adjusting for age, grade, stage (RFD: 11.3%; 95% CI: 7.6, 15.0). Associations were attenuated and non-significant when measured by IHC. IHC-based TP53 status is an insensitive measurement of TP53 functional status. RNA-based methods suggest a role for TP53 in tumor prognostic features and racial disparities., Competing Interests: Charles M. Perou is an equity stock holder of BioClassifier LLC and University Genomics and filed a patent on the PAM50 intrinsic breast cancer subtyping assay.

Background: Smoking is a possible risk factor for breast cancer and has been linked to increased risk of estrogen receptor-positive (ER + ) disease in some epidemiologic studies. It is unknown whether smoking has quantitative effects on ER expression. Methods: We examined relationships between smoking and ER expression from tumors of 1,888 women diagnosed with invasive breast cancer from a population-based study in North Carolina. ER expression was characterized using binary (±) and continuous measures for ER protein, ESR1 mRNA, and a multigene luminal score (LS) that serves as a measure of estrogen signaling in breast tumors. We used logistic and linear regression models to estimate temporal and dose-dependent associations between smoking and ER measures. Results: The odds of ER + , ESR1 + , and LS + tumors among current smokers (at the time of diagnosis), those who smoked 20 or more years, and those who smoked within 5 years of diagnosis were nearly double those of nonsmokers. Quantitative levels of ESR1 were highest among current smokers compared with never smokers overall [mean (log 2 ) = 9.2 vs. 8.7, P < 0.05] and among ER + cases; however, we did not observe associations between smoking measures and continuous ER protein expression. Conclusions: In relationship to breast cancer diagnosis, recent smoking was associated with higher odds of the ER + , ESR1 + , and LS + subtype. Current smoking was associated with elevated ESR1 mRNA levels and an elevated LS, but not with altered ER protein. Impact: A multigene LS and single-gene ESR1 mRNA may capture tumor changes associated with smoking. Cancer Epidemiol Biomarkers Prev; 27(1); 67-74. ©2017 AACR ., (©2017 American Association for Cancer Research.)

To help tobacco control research better include vulnerable populations, we sought to identify effective ways to recruit diverse smokers. In 2014-2015, we recruited 2149 adult cigarette smokers in California and North Carolina, United States, to participate in a randomized trial of pictorial cigarette pack warnings. The most effective means of recruiting smokers were the classified advertising website Craigslist (28% of participants), word of mouth (23%), Facebook (16%), and flyers or postcards (14%). Low-income and African American smokers were more likely to respond to interpersonal contact (including staff in-person recruitment and word of mouth) than were high-income and non-African American smokers (all p < 0.05). Hispanic and gay, lesbian, and bisexual smokers were more likely to be recruited by Craigslist than non-Hispanic and straight smokers (both p < 0.05). Of the recruitment methods requiring cost, the cheapest was Craigslist ($3-7 per smoker). The most expensive methods were newspaper ads in California ($375 per smoker) and staff in-person recruiting in North Carolina ($180 per smoker). Successfully recruiting diverse smokers requires using multiple methods including interpersonal, online, and other media. Craigslist and word of mouth are especially useful and low-cost ways to recruit diverse smokers., Competing Interests: The authors declare no conflicts of interest.

Purpose: Growing evidence suggests an association between active cigarette smoking and increased breast cancer risk. However, the weak magnitude of association and conflicting results have yielded uncertainty and it is unknown whether associations differ by breast cancer subtype., Methods: Using population-based case-control data from phases I and II of the Carolina Breast Cancer Study, we examined associations between self-reported measures of smoking and risk of Luminal and Basal-like breast cancers. We used logistic regression models to estimate case-control odds ratios (OR) and 95 % confidence intervals (CI)., Results: Ever smoking (current and former) was associated with a weakly increased risk of Luminal breast cancer (OR 1.12, 95 % CI 0.92-1.36) and was not associated with risk of Basal-like breast cancer (OR 0.96, 95 % CI 0.69-1.32). Similarly, smoking duration of more than 20 years was associated with increased risk of Luminal (OR 1.51, 95 % CI 1.19-1.93), but not Basal-like breast cancer (OR 0.90, 95 % CI 0.57-1.43). When stratified by race, elevated odds ratios between smoking and Luminal breast cancer risk were found among black women across multiple exposure measures (ever smoking, duration, and dose); conversely, among white women odds ratios were attenuated or null., Conclusions: Results from our study demonstrate a positive association between smoking and Luminal breast cancer risk, particularly among black women and women with long smoking histories. Addressing breast cancer heterogeneity in studies of smoking and breast cancer risk may elucidate associations masked in prior studies.

Purpose: Medicare beneficiaries with cancer bear a greater portion of their health care costs, because cancer treatment costs have increased. Beneficiaries have supplemental insurance to reduce out-of-pocket costs; those without supplemental insurance may face barriers to care. This study examines the association between type of supplemental insurance coverage and receipt of chemotherapy among Medicare patients with cancer who, per National Comprehensive Cancer Network treatment guidelines, should generally receive chemotherapy., Patients and Methods: This retrospective, observational study included 1,200 Medicare patients diagnosed with incident cancer of the breast (stage IIB to III), colon (stage III), rectum (stage II to III), lung (stage II to IV), or ovary (stage II to IV) from 2000 to 2005. Using the National Cancer Institute Patterns of Care Studies and linked SEER-Medicare data, we determined each Medicare patient's supplemental insurance status (private insurance, dual eligible [ie, Medicare with Medicaid], or no supplemental insurance), consultation with an oncologist, and receipt of chemotherapy. Using adjusted logistic regression, we evaluated the association of type of supplemental insurance with oncologist consultation and receipt of chemotherapy., Results: Dual-eligible patients were significantly less likely to receive chemotherapy than were Medicare patients with private insurance. Patients with Medicare only who saw an oncologist had comparable rates of chemotherapy compared with Medicare patients with private insurance., Conclusion: Dual-eligible Medicare beneficiaries received recommended cancer chemotherapy less frequently than other Medicare beneficiaries. With the increasing number of Medicaid patients under the Affordable Care Act, there will be a need for patient navigators and sufficient physician reimbursement so that low-income patients with cancer will have access to oncologists and needed treatment., (© 2014 by American Society of Clinical Oncology.)

Background: Physical activity (PA) is recommended for primary and secondary prevention of cardiovascular disease (CVD). This study described the prevalence of self-reported and accelerometer-measured PA and sedentary behavior, using a nationally representative sample from the United States, a subset of whom had CVD, including angina, coronary heart disease (CHD), congestive heart failure (CHF), and myocardial infarction (MI)., Methods: Using the most recently available accelerometer data (combined 2003-2006) from the National Health and Nutrition Examination Survey, the study sample included 680 adults with CVD, who completed a questionnaire and wore an ActiGraph accelerometer for 1 week. A group without CVD (n = 1000) was also selected as the referent, with similar age, gender, and race/ethnic distributions as those with CVD (angina, CHD, CHF, MI) to compare PA and sedentary behavior estimates. Percentages and means were weighted to reflect the US population from 2003 to 2006., Results: Among those with CVD, the proportion of individuals who engaged in self-reported past-month, moderate-intensity leisure activity ranged from 39.7% (CHF) to 53.8% (CHD) and vigorous-intensity leisure activity from 12.9% (CHF) to 18.4% (CHD), with walking being the most commonly reported activity. Television watching ≥4 h/d ranged from 36.2% (MI) to 44.8% (CHF). Using accelerometry, moderate- to vigorous-intensity PA ranged from 8.6 (CHF) to 11.4 min/d (angina). Sedentary behavior ranged from 9.6 (angina) to 10.1 h/d (CHF). All 4 CVD groups had lower leisure activity and moderate- to vigorous-intensity PA, and higher television watching and sedentary behavior, when compared with the referent group., Conclusions: Further efforts are needed to encourage PA and reduce sedentary behavior for secondary prevention of CVD.

Background: The risk of stroke is greatest among adults who have experienced a previous stroke, transient ischemic attack, or myocardial infarction. Physical activity may reduce the secondary risk of stroke through mediating effects on blood pressure, vasoconstriction, and circulating lipid concentrations; however, little is known about the prevalence of physical activity and sedentary behavior among stroke survivors in the United States., Methods: Using data from the National Health and Nutrition Examination Survey (NHANES), we describe self-reported and objectively measured physical activity and sedentary behavior among adults with a self-reported history of stroke. We also contrast physical activity among stroke survivors with that of adults without stroke (unexposed) to illustrate expected behavior in the absence of disease., Results: Fewer participants with stroke met weekly physical activity guidelines as outlined in the 2008 Physical Activity Guidelines for Americans when compared with unexposed participants (17.9% vs 25.0%) according to self-reported data. In addition, participants with stroke reported less moderate (46.1% vs 54.7%) and vigorous (9.1% vs 19.6%) leisure activity compared with unexposed participants. As measured by accelerometer, time since diagnosis was inversely associated with physical activity engagement, and participants with stroke recorded more daily hours of sedentary behavior compared with unexposed participants (10.1 hours vs 8.9 hours)., Conclusion: Findings from this study provide a basis for future work seeking to measure the impact of physical activity on the secondary prevention of stroke by characterizing the prevalence of physical activity and sedentary behavior among stroke survivors in the United States.

Context: The existing evidence on food environments and diet is inconsistent, potentially because of heterogeneity in measures used to assess diet. The objective of this review, conducted in 2012-2013, was to examine measures of dietary intake utilized in food environment research., Evidence Acquisition: Included studies were published from January 2007 through June 2012 and assessed relationships between at least one food environment exposure and at least one dietary outcome. Fifty-one articles were identified using PubMed, SCOPUS, Web of Knowledge, and PsycINFO; references listed in the papers reviewed and relevant review articles; and the National Cancer Institute's Measures of the Food Environment website. The frequency of the use of dietary intake measures and assessment of specific dietary outcomes were examined, as were patterns of results among studies using different dietary measures., Evidence Synthesis: The majority of studies used brief instruments, such as screeners or one or two questions, to assess intake. Food frequency questionnaires were used in about a quarter of studies, one in ten used 24-hour recalls, and fewer than one in 20 used diaries. Little consideration of dietary measurement error was evident. Associations between the food environment and diet were more consistently in the expected direction in studies using less error-prone measures., Conclusions: There is a tendency toward the use of brief dietary assessment instruments with low cost and burden rather than more detailed instruments that capture intake with less bias. Use of error-prone dietary measures may lead to spurious findings and reduced power to detect associations., (© 2013 American Journal of Preventive Medicine Published by American Journal of Preventive Medicine All rights reserved.)

Colorectal cancer is the third most common cancer in the United States and Canada. Given the high incidence and increased survival of colorectal cancer patients, prevalence is increasing over time in both countries. Using MEDLINE, we conducted a systematic review of the literature published between 2000 and 2010 to describe patterns of colorectal cancer care. Specifically we examined data sources used to obtain treatment information and compared patterns of cancer-directed initial care, post-diagnostic surveillance care, and end-of-life care among colorectal cancer patients diagnosed in the United States and Canada. Receipt of initial treatment for colorectal cancer was associated with the anatomical position of the tumor and extent of disease at diagnosis, in accordance with consensus-based guidelines. Overall, care trends were similar between the United States and Canada; however, we observed differences with respect to data sources used to measure treatment receipt. Differences were also present between study populations within country, further limiting direct comparisons. Findings from this review will allow researchers, clinicians, and policy makers to evaluate treatment receipt by patient, clinical, or system characteristics and identify emerging trends over time. Furthermore, comparisons between health-care systems in the United States and Canada can identify disparities in care, allow the evaluation of different models of care, and highlight issues regarding the utility of existing data sources to estimate national patterns of care.

Colorectal cancer is the second most common cancer in women and the third most common in men worldwide. In this study, we used MEDLINE to conduct a systematic review of existing literature published in English between 2000 and 2010 on patterns of colorectal cancer care. Specifically, this review examined 66 studies conducted in Europe, Australia, and New Zealand to assess patterns of initial care, post-diagnostic surveillance, and end-of-life care for colorectal cancer. The majority of studies in this review reported rates of initial care, and limited research examined either post-diagnostic surveillance or end-of-life care for colorectal cancer. Older colorectal cancer patients and individuals with comorbidities generally received less surgery, chemotherapy, or radiotherapy. Patients with lower socioeconomic status were less likely to receive treatment, and variations in patterns of care were observed by patient demographic and clinical characteristics, geographical location, and hospital setting. However, there was wide variability in data collection and measures, health-care systems, patient populations, and population representativeness, making direct comparisons challenging. Future research and policy efforts should emphasize increased comparability of data systems, promote data standardization, and encourage collaboration between and within European cancer registries and administrative databases.

Background: Examining relationships between features of the built environment and physical activity is achievable with geographic information systems technology (GIS). The purpose of this paper is to review the literature to identify GIS measures that can be considered for inclusion in national public health surveillance efforts. In the absence of a universally agreed upon framework that integrates physical, social, and cultural aspects of the environment, we used a multidimensional model of access to synthesize the literature., Methods: We identified 29 studies published between 2005 and 2009 with physical activity outcomes that included 1 or more built environment variables measured using GIS. We sorted built environment measures into 5 dimensions of access: accessibility, availability, accommodation, affordability, and acceptability., Results: Geospatial land-use data, street network data, environmental audits, and commercial databases can be used to measure the availability, accessibility, and accommodation dimensions of access. Affordability and acceptability measures rely on census and self-report data., Conclusions: GIS measures have been included in studies investigating the built environment and physical activity, although few have examined more than 1 construct of access. Systematic identification and collection of relevant GIS measures can facilitate collaboration and accelerate the advancement of research on the built environment and physical activity.

Background: Although US year 2000 guidelines recommended characterizing breast cancers by human epidermal growth factor receptor 2 (HER2), national cancer registries do not collect HER2, rendering a population-based understanding of HER2 and clinical "triple subtypes" (estrogen receptor [ER] / progesterone receptor [PR] / HER2) largely unknown. We document the population-based prevalence of HER2 testing / status, triple subtypes and present the first report of subtype incidence rates., Methods: Medical records were searched for HER2 on 1842 metropolitan Atlanta females diagnosed with breast cancer during 2003-2004. HER2 testing/status and triple subtypes were analyzed by age, race/ethnicity, tumor factors, socioeconomic status, and treatment. Age-adjusted incidence rates were calculated., Results: Over 90% of cases received HER2 testing: 12.6% were positive, 71.7% negative, and 15.7% unknown. HER2 testing compliance was significantly better for women who were younger, of Caucasian or African-American descent, or diagnosed with early stage disease. Incidence rates (per 100,000) were 21.1 for HER2+ tumors and 27.8 for triple-negative tumors, the latter differing by race (36.3 and 19.4 for black and white women, respectively)., Conclusions: HER2 recommendations are not uniformly adhered to. Incidence rates for breast cancer triple subtypes differ by age/race. As biologic knowledge is translated into the clinical setting eg, HER2 as a biomarker, it will be incumbent upon national cancer registries to report this information. Incidence rates cautiously extrapolate to an annual burden of 3000 and 17,000 HER2+ tumors for black and white women, respectively, and triple-negative tumors among 5000 and 16,000 respectively. Testing, rate, and burden variations warrant population-based in-depth exploration and clinical translation., ((c) 2010 American Cancer Society.)

Background: A new pandemic influenza A (H1N1) virus has emerged, causing illness globally, primarily in younger age groups. To assess the level of preexisting immunity in humans and to evaluate seasonal vaccine strategies, we measured the antibody response to the pandemic virus resulting from previous influenza infection or vaccination in different age groups., Methods: Using a microneutralization assay, we measured cross-reactive antibodies to pandemic H1N1 virus (2009 H1N1) in stored serum samples from persons who either donated blood or were vaccinated with recent seasonal or 1976 swine influenza vaccines., Results: A total of 4 of 107 persons (4%) who were born after 1980 had preexisting cross-reactive antibody titers of 40 or more against 2009 H1N1, whereas 39 of 115 persons (34%) born before 1950 had titers of 80 or more. Vaccination with seasonal trivalent inactivated influenza vaccines resulted in an increase in the level of cross-reactive antibody to 2009 H1N1 by a factor of four or more in none of 55 children between the ages of 6 months and 9 years, in 12 to 22% of 231 adults between the ages of 18 and 64 years, and in 5% or less of 113 adults 60 years of age or older. Seasonal vaccines that were formulated with adjuvant did not further enhance cross-reactive antibody responses. Vaccination with the A/New Jersey/1976 swine influenza vaccine substantially boosted cross-reactive antibodies to 2009 H1N1 in adults., Conclusions: Vaccination with recent seasonal nonadjuvanted or adjuvanted influenza vaccines induced little or no cross-reactive antibody response to 2009 H1N1 in any age group. Persons under the age of 30 years had little evidence of cross-reactive antibodies to the pandemic virus. However, a proportion of older adults had preexisting cross-reactive antibodies., (2009 Massachusetts Medical Society)

Pseudotype reporter viruses provide a safe, quantitative, and high-throughput tool for assessing antibody neutralization for many viruses, including high pathogenicity H5 and H7 influenza A strains. However, adapting this system to other influenza subtypes has been hampered by variations in the protease cleavage site of hemagglutinin (HA) that make it less susceptible to the cleavage required for infectivity. In this report several proteases, reporter vectors, and cell substrates were evaluated while optimizing pseudovirus production, and robust methods were established for sensitive and specific neutralization of pseudotypes carrying influenza H1, H3, and H5 subtype HA that correlates well with titers obtained in microneutralization assays involving replicating influenza virus These findings should facilitate broad use of HA-pseudotypes that remove the need for infectious virus in a range of applications, including neutralization assays for serological surveys of viral infection and evaluations of vaccine sera.

The surveillance of seasonal influenza virus susceptibility to neuraminidase (NA) inhibitors was conducted using an NA inhibition assay. The 50% inhibitory concentration values (IC(50)s) of 4,570 viruses collected globally from October 2004 to March 2008 were determined. Based on mean IC(50)s, A(H3N2) viruses (0.44 nM) were more sensitive to oseltamivir than A(H1N1) viruses (0.91 nM). The opposite trend was observed with zanamivir: 1.06 nM for A(H1N1) and 2.54 nM for A(H3N2). Influenza B viruses exhibited the least susceptibility to oseltamivir (3.42 nM) and to zanamivir (3.87 nM). To identify potentially resistant viruses (outliers), a threshold of a mean IC(50) value + 3 standard deviations was defined for type/subtype and drug. Sequence analysis of outliers was performed to identify NA changes that might be associated with reduced susceptibility. Molecular markers of oseltamivir resistance were found in six A(H1N1) viruses (H274Y) and one A(H3N2) virus (E119V) collected between 2004 and 2007. Some outliers contained previously reported mutations (e.g., I222T in the B viruses), while other mutations [e.g., R371K and H274Y in B viruses and H274N in A(H3N2) viruses) were novel. The R371K B virus outlier exhibited high levels of resistance to both inhibitors (>100 nM). A substantial variance at residue D151 was observed among A(H3N2) zanamivir-resistant outliers. The clinical relevance of newly identified NA mutations is unknown. A rise in the incidence of oseltamivir resistance in A(H1N1) viruses carrying the H274Y mutation was detected in the United States and in other countries in the ongoing 2007 to 2008 season. As of March 2008, the frequency of resistance among A(H1N1) viruses in the United States was 8.6% (50/579 isolates). The recent increase in oseltamivir resistance among A(H1N1) viruses isolated from untreated patients raises public health concerns and necessitates close monitoring of resistance to NA inhibitors.

Background: A disparate proportion of breast cancer deaths occur among young women, those of African-American (AA) ancestry, and particularly young AA women. Estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor-2 (HER-2) are key clinically informative biomarkers. The triple-negative (ER-/PR-/HER-2-) tumor subgroup is intrinsically resistant to treatment and portends a poor prognosis. Age, race, and socioeconomic status have been associated with triple-negative tumors (TNT). In the current study, the authors investigated breast cancer subgroups among patients in an urban cancer center serving a multiracial, low socioeconomic population., Methods: This case series analyzed female invasive breast cancers diagnosed and/or treated between 2003 and 2004 in the AVON Comprehensive Breast Center at Grady Hospital in Atlanta, Georgia. Data were obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program, and augmented by the hospital registry and pathology reports. Statistical analyses utilized frequency distributions and logistic regression., Results: Of 190 breast cancers; 167 (88%) were diagnosed among AA and 23 (12%) were diagnosed among non-AA women. The median age at diagnosis in the 2 groups was 58 years and 57 years, respectively. TNT prevalence was found to differ by race (29.3% among AA women and 13.0% among non-AA women; P = .010). Differences persisted after adjustment for age and stage (odds ratio [OR] of 3.1; 95%confidence interval [95% CI], 0.8-11.6). The majority of recurrences (40.0%) occurred among women with TNT, who were also most likely to experience a fatal event (OR of 3.7; 95%CI, 1.1-13.0)., Conclusions: Despite a similarity in their age at diagnosis, AA women in our urban cancer center presented with a higher prevalence of TNT and TNT was found to predict the poorest outcomes. Institutional interactive breast conferences and intervention/navigation programs could help to dispel breast cancer disparities and improve outcomes., ((c) 2008 American Cancer Society)

Exposure of cultured bovine pulmonary artery endothelial cells to hyperoxia (95% O2) caused cellular injury manifested by decreased growth rates and release of cytoplasmic lactic dehydrogenase (LDH). In addition, a greater number of polymorphonuclear leukocytes (PMN) adhered to endothelial cells that had been exposed to hyperoxia for 24 or 48 h than to control endothelial cells that had been exposed to normoxia (15% O2). Direct endothelial cell injury from hyperoxia may contribute to vascular damage and the increased PMN accumulation seen in lungs of animals exposed to hyperoxia.

Zwitterion buffers are often used to modulate the pH of cell culture medium but their effect on cultured cells is controversial. We found that addition of 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) caused superoxide dismutase (SOD) inhibitable increases in nitroblue tetrazolium dye reduction and SOD and catalase inhibitable decreases in the growth of cultured bovine pulmonary artery endothelial cells. The findings suggest that HEPES stimulates endothelial cells to make toxic oxygen metabolites that contribute to decreased cell growth.