bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation of a low-dose computerized tomography (LDCT) lung cancer screening program (LCSP) across a large integrated health system.
Authors: Bjegovich-Weidman Marija , Leh Steven , Malone Daniel , Mendoza-Ayala Raul , Barry-Weers Anne Marie , Dlouhy Laurie , Wesolowski Jody , Mitchell Dorry , Clement Kevin , Amy Bock , Weese James L. 
Published: May 2019

1537 Background: The LDCT LCSP was launched as a critical component of our Cancer Program to support tobacco cessation efforts and increase early detection. Initially it was offered as a self-referral low cost screening. The program was expanded when the Affordable Care Act and Center for Medicare/Medicaid Services covered it as a preventative services benefit in January 2015. Methods: 9 LDCT LCSP locations were implemented between 2014-September 2016. Program data are submitted to the American College of Radiology Lung Cancer Data Registry since 2016. In 2017, a Best Practice Alert was created within our electronic health record (EHR) to alert the primary care clinician if his/her patient met criteria for a LDCT. Each of the sites managed their own programs up until September 2018 when a dedicated team (Team) of two nurses and one data support specialist was justified. The Team focus is to increase awareness of the LDCT LCSP and criteria for eligibility, improve tobacco history taking and pack year documentation in the EHR, increase smoking cessation counseling and referral, and facilitate presentation of all Lung RADS category 4 cases for review at one of our two Multidisciplinary Lung Cancer Case Conferences. Standardized management of key incidental findings was developed for coronary artery calcification, non-lung masses, thoracic aortic aneurysm, and critical pulmonary conditions. To date, we have not examined the impact of the LDCT LCSP on smoking cessation rates. All 9 program sites have been named a Screening Center of Excellence by the Lung Cancer Alliance. Results: In 2016, 1849 LDCT Screenings were performed, 4701 (154% increase) in 2017 and 7154 (52.5% increase) in 2018. Cancer Detection rates were 1.3% in 2016, 1.8% in 2017 and 1.3% for January-June 2018. Cancer registry data reports a 9% increase in Stage 0, 1, 2A and a 7.2% decrease in Stage IV at time of diagnosis from 2014-2017. Conclusions: The implementation of a LDCT LCSP has increased the percentage of patients diagnosed at an earlier stage of lung cancer. With standardized management of key incidental findings, we anticipate improvement in early detection and management of cardiac and pulmonary diseases.
Analysis of healthy breast tissue from Komen Tissue Bank shows distinct histology, decreased proliferation, and lower periductal collagen deposition in women with prolonged history of breastfeeding.
Authors: Basree Mustafa , Shinde Neelam , Li Zaibo , Majumder Sarmila , Ramaswamy Bhuvaneswari 
Published: May 2019

1538 Background: Epidemiological studies have shown that prolonged breastfeeding is associated with a reduced risk of developing triple negative/basal-like breast cancer (TN/BLBC). We have modeled abrupt involution (AI) following short breastfeeding and gradual involution (GI) of the mammary gland that occurs over time upon prolonged breastfeeding in wild-type FVB/N mice and discovered prominent histological and molecular changes in the AI glands over time. Further, we demonstrated that breast tissue from healthy women who breastfed <6 months showed enrichment in stem-cell and cell renewal pathways. Here, we corroborate those studies using normal human breast tissue obtained from Susan G. Komen for the Cure Tissue Bank (KTB). Methods: FFPE breast tissue sections obtained from KTB (Protocol #2017CO184). Donors were parous women, aged 18 to 45, without history of breast cancer and for whom breastfeeding history was available. H&E sections and TDLU, the primary anatomical source of most breast cancers, of women who breastfed for ≥6 months (GI, n=49) vs. those who breastfed for ≤3 months (AI, n=20) were evaluated by a blinded pathologist. Masson Trichrome stain was used to measure collagen deposition. Ki67 immunohistochemistry was utilized to determine proliferation. Statistical significance was measured using Fisher’s exact t-test and two-sample t-test with a p-value of <0.05. Results: H&E analysis revealed that breast tissue obtained from women in the AI cohort exhibited histological features of inflammation (p-value= 0.025). Using Ki67 IHC (AI, n=15; GI, n=32) and Masson Trichome stain (AI, n=3; GI, n=4), sections in the AI cohort showed 2-fold increase in proliferation of lobular epithelium (p-value= 0.048) and 1.4-fold increase in periductal collagen deposition (p-value= 0.027) when compared to GI cohort. Age, race, and BMI were not statistically different between AI and GI cohorts. Conclusions: Breast tissue from parous women who breastfed ≤3 months is histologically different than tissue of women with ≥6 months history of breastfeeding. We are currently staining more breast tissue samples obtained from KTB. Experiments are underway to assess the long-term effect of breastfeeding on breast epithelial cell hierarchy and biomarkers of inflammation. Understanding this mechanistic link will help in developing prevention strategies, particularly for African-American women who have lower prevalence of breastfeeding and higher incidence of TN/BLBC.
The impact of smoking cessation on breast cancer patients’ survival.
Authors: Jizzini Mazen , Raghavendra Akshara Singareeka , Ibrahim Nuhad K. , Kypriotakis George , Cinciripini Paul M. , Seoudy Kareem , Karam-Hage Maher A. 
Published: May 2019

1542 Background: Breast cancer remains to be one of the highest causes of cancer mortality amongst females globally, second only to lung cancer. Smoking is strongly associated with increased all-cause mortality, including breast cancer related death. It has also been shown to have a negative influence on long-term survival after successful breast cancer treatment. Prior studies have shown that smoking cessation may lead to improved prognosis and better outcomes. Methods: This is a retrospective cohort study of breast cancer patients who were identified as smokers, some of who were referred to the tobacco treatment program (TTP) located at MD Anderson Cancer Center. TTP includes careful patient screening, motivational counseling, and pharmacotherapy. We complemented the original data collected by conducting in-depth chart reviews to extract data including patient demographics, date of diagnosis, stage of cancer, smoking status, duration of abstinence and dates of follow-up or death. We then examined associations between smoking status and survival status using multinomial regression models adjusting for biomarkers of disease and personal characteristics. Results: Among all breast cancer patients (N = 31069), we identified those who are smokers (n = 2320) by matching the TTP database with smoking status from our institutional electronic health records. Of those, 740 patients were referred to TTP. Amongst these, 242 patients quit smoking and remained abstinent at the 9 month follow-up. Compared with non-abstainers, those who quit were more likely to be alive with no evidence of disease during the observation time (RR = 1.62, p = 0.045). When analyzed at different stages, the RR went from 1.35 (p = 0.42) to 2.77 (p = 0.34) for stages 3 and 1, respectively. Although the strength of this relationship varied among disease stage, the direction of the relationship remain consistent. Conclusions: Our data shows that smoking cessation is associated with improved survival status amongst breast cancer survivors across all stages. Comprehensive smoking cessation services may improve survivorship when started as early as the time of diagnosis. Further analysis of the association between smoking cessation and other associated medical outcomes will be conducted to further determine the specific impact of cessation programs.
Improving risk assessment of obesity-associated breast cancer.
Authors: Iyengar Neil M. , Gucalp Ayca , Zhou Xi K. , Wang Hanhan , Giri Dilip D. , Williams Samantha , Falcone Domenick J. , Winston Lisle , Landa Jonathan , Kirstein Laurie J. , Morrow Monica , Dannenberg Andrew J. 
Published: May 2019

1544 Background: Elevated body mass index (BMI) is associated with increased risk of estrogen receptor (ER)-positive postmenopausal breast cancer. The risk is also elevated in women with a normal BMI but excess body fat. These risks may be driven by breast white adipose tissue inflammation (WATi), which is associated with elevated aromatase levels and systemic metabolic dysfunction (e.g. hyperinsulinemia). We hypothesized that body fat assessment is superior to BMI for detecting the pathophysiology that promotes obesity-related breast cancer, particularly among normal BMI women. Methods: Non-tumorous breast tissue was collected from women undergoing mastectomy for breast cancer treatment or prevention. Breast WATi was detected by the presence of crown-like structures in the breast, which are composed of a dead/dying adipocyte surrounded by CD68+ macrophages. Body composition was measured prior to mastectomy via dual energy X-ray absorptiometry. Exercise behavior was also assessed prior to surgery using the Godin Leisure Time Exercise Questionnaire. Associations among categorical variables were examined using Χ2 or Fisher’s exact test. Relationships between continuous variables were examined using the Spearman correlation. Results: From April 5, 2016 to August 31, 2018, 100 patients were enrolled; median age 49 (range 29 to 82) years. Breast WATi was present in 56/100 (56%) women and was associated with elevated BMI and body fat levels, breast adipocyte hypertrophy, postmenopausal status, metabolic syndrome and decreased physical activity (P < 0.05). Among 39 women with normal BMI, breast WATi was present in 14 (36%) and was associated with elevated body fat levels, breast adipocyte hypertrophy, dyslipidemia, and decreased physical activity (P < 0.05). There was no statistically significant association between BMI and breast WATi in the normal BMI group. Menopausal status and total fat mass had greater sensitivity and specificity for the detection of breast WATi compared to a BMI-based model (AUC 0.843 vs. 0.779, respectively). Conclusions: Measurement of body fat is superior to BMI for predicting breast inflammation, which has been shown to promote obesity-related breast cancer.
Comparison of risk-reducing surgery in women with BRCA and non-BRCA ovarian cancer susceptibility genes.
Authors: Schwartz Zachary Phillip , Zakhour Mae , Li Andrew John , Walsh Christine S. , Rimel Bj , Alvarado Monica , Lentz Scott E , Cass Ilana 
Published: May 2019

1547 Background: Risk reducing gynecologic surgery (RRSO) is standard of care for women with BRCA mutations. The optimal management for women with non-BRCA ovarian cancer susceptibility mutations remains unclear. We sought to characterize the practice patterns for these women at our two institutions. Methods: Women with germline ovarian cancer susceptibility genes who had a RRSO were identified from 1/2000-1/2019 in an IRB approved study. All patients were asymptomatic with no suspicion for malignancy at time of RRSO. Clinico-pathologic characteristics were extracted from the medical records. Continuous variables were analyzed with Kruskal-Wallis and categorical variables analyzed with chi square and t-tests. Results: 152 BRCA1, 95 BRCA2, and 63 Non-BRCA mutation carriers were identified—50 Lynch (22 MLH1, 13 MSH2, 13 MSH6, 2 PMS2) and 13 Other (6 BRIP1, 2 RAD51C, 5 RAD51D). There was no difference between age at testing, age at RRSO, and interval between testing and RRSO between groups. Genetic counseling was higher in Non-BRCA patients. Family history of ovarian cancer was more common in women with BRCA1 and Other germline mutations compared to BRCA2 and Lynch. Family and personal history of breast cancer was high in all groups except Lynch carriers. Prophylactic mastectomy was seen mostly in BRCA mutation carriers. Concomitant hysterectomy was performed in the majority of women (BRCA1 59%, BRCA2 57%, and Other 62%), with the highest frequency in Lynch carriers (86%, p<.01). Occult cancer was only seen in BRCA mutation carriers: BRCA1 (7%), BRCA2 (2%), Lynch (0%), Other (0%). Conclusions: In this cohort, women with Non-BRCA mutations are managed similarly to women with BRCA mutations. We observed no occult cancers in Non-BRCA patients. The optimal role of surgery as a risk reducing strategy in this group requires further study. [Table: see text]
Association between breast cancer mortality-to-incidence ratios and state health disparities in the United States.
Authors: Lee Yu-Che , Chang Ko-Yun , Hurley Judith 
Published: May 2019

1548 Background: Breast cancer is the most commonly diagnosed cancer and second leading cause of cancer deaths among women in the United States. The cancer mortality-to-incidence ratio (MIR) provides a population-based indicator of cancer survival and has been established previously to evaluate healthcare variations among different countries. We aim to evaluate the association, which has not been investigated before, between MIR of breast cancer and state-level health disparities in the United States. Methods: We used United States Cancer Statistics (USCS) database to calculate 6-year average of MIRs for breast cancer from 2010 to 2015. America’s Health Rankings (AHR) is a platform using weighted measures in 5 different categories (Behaviors, Community & Environment, Policy, Clinical Care and Outcomes) to determine annual state health rankings. Six-year average (2010-2015) of health uninsured rate by state was obtained from the U.S. Census Bureau and 5-year average (2010-2014) of health spending per capita by state was obtained from Centers for Medicare & Medicaid Services. The correlations between breast cancer MIRs and state health variables were calculated by linear regression analyses. Results: From 2010 through 2015, 1,390,357 females were diagnosed with breast cancer and 246,671 females died from breast cancer in the United States. The 6-year average of age-adjusted incidence rate, mortality rate and MIRs were 124.2 ± 1.3 per 100,000 population, 21.1 ± 0.6 per 100,000 and 0.170 ± 0.007, respectively. Among fifty states we included for analyses, Hawaii had the lowest MIR (0.116 ± 0.014) and Nevada had the highest MIR (0.204 ± 0.004). AHR showed Hawaii had the highest health ranking (No. 1) whereas Louisiana had the lowest health ranking (No. 50) in 2015. In our analysis, states with better health rankings, lower health uninsured rates and higher health spending per capita were significantly correlated with lower MIRs (R2 = 0.695, 0.453 and 0.253, respectively; all P < 0.001). Conclusions: The difference of MIRs for breast cancer was strongly associated with state health diversities. These findings suggest that MIR of breast cancer can be an applicable measure to evaluate and reflect the state-level health disparities in the United States. [Table: see text]
Epidemiology and survival in patients with urethral clear cell carcinoma.
Authors: Patel Mausam , Im Jay , Ivy Austin , Maraboyina Sanjay , Kim Thomas 
Published: May 2019

1550 Background: Clear cell carcinoma (CCC) of the urethra is a very rare histologic variant of urethral adenocarcinoma. The majority of studies have been case reports and case series with no large population based studies. A retrospective analysis was performed with the National Cancer Institute’s (NCI) Surveillance, Epidemiology, and End Results (SEER) database to establish the epidemiology of urethral CCC and determine the clinical factors associated with survival. Methods: All cases of clear cell carcinoma of the urethra diagnosed from January 1, 1973 to December 31, 2014 were extracted from SEER. Age at diagnosis, sex, marital status, race, grade, stage, surgery, radiation, chemotherapy, overall survival (OS), disease specific survival (DSS), and survival months were extracted for analysis. Descriptive statistics were calculated for all variables. Univariable analysis to assess for differences in survival with respect to covariates was performed using the log rank test. Multivariable analysis was performed with Cox proportional hazards regression models to determine the predictive performance of covariates with respect to OS and DSS, reported as hazard ratio [HR] with 95% CIs. Comparisons were considered statistically significant at P < 0.05. Results: Sixty one cases were extracted for analysis. The mean ± SD was 63.0 ± 13.9 years. Fifty eight (95.1%) patients were female with 53 (86.8%) locoregional cases at presentation. There were 50 (82%), 18 (29.5%), and 12 (23.0%) patients who underwent surgery, radiation, and chemotherapy, respectively. On univariable analysis, the following covariates were associated with both OS and DSS: age, stage, and surgery (all p < 0.001; log rank test). On multivariable analysis, surgery was a predictor for improved OS and DSS (HR, 0.178; 95% CI [0.068; 0.464]) and HR, 0.166; 95% CI [0.196; 2.132], respectively). Additionally, both increasing age and distant disease were associated with worse OS and DSS. Neither radiation nor chemotherapy were significantly associated with OS or DSS. Conclusions: Surgery improves OS and DSS in patients with urethral CCC. While neither radiation nor chemo were significantly associated with survival, additional studies are necessary to determine how these therapeutic interventions may impact prognosis.
Association of geographic clustering of cutaneous T-cell lymphoma in the state of Georgia with environmental exposure to benzene and trichloroethylene.
Authors: Allen Pamela Blair , Clough Lindsay , Bayakly A. Rana , Ward Kevin C. , Khan Mohammad Khurram , Chen Suephy , Flowers Christopher , Switchenko Jeffrey M. 
Published: May 2019

1551 Background: Geographic clustering of CTCL has been recently reported in large registries, but its association with environment factors is unknown. Benzene and trichloroethylene (TCE) are two common carcinogenic environmental toxins associated with hematological cancers. We investigated associations between geographic clustering of CTCL incidence in the state of Georgia with benzene and TCE exposure. Methods: We obtained county-level incidence of CTCL within Georgia from the Georgia Cancer Registry between 1999-2015. To account for the demographic structure in each county, standardized incidence ratios (SIR) were calculated by dividing the observed number of cases of CTCL in Georgia by the expected number of cases using national incidence rates by age, sex, and race. Using spatial analyses, we assessed for population-adjusted county-level clustering of SIRs. We also recorded county-level exposure concentration of benzene and TCE between 1996-2014 from the EPA’s National Air Toxics Assessment database. Linear regression analyses on CTCL incidence were performed comparing SIRs to exposure levels of benzene and TCE by county. Results: Our analyses demonstrated significant geographic clustering of CTCL in Georgia (Moran’s I statistic 0.0991, p-value = 0.022). Local spatial tests revealed several statistically significant hot spots throughout Georgia, particularly around Atlanta. This clustering was strongly correlated with benzene (R2 0.0824, p-value 0.0006) and TCE (R2 0.0614, p-value 0.0016) exposure concentration. Among the four most populous counties in Georgia (Cobb, Dekalb, Fulton, and Gwinnett) CTCL incidence was 1.7 to 2.7 times higher than the average county, and benzene and TCE exposure concentration was 3.0 to 6.3 times higher. Conclusions: These results demonstrate non-random geographic clustering of CTCL incidence in Georgia. This is the first analysis to correlate geographic clustering of CTCL with environmental toxic exposures, demonstrating a statistically significant correlation between environmental exposure to benzene and TCE and CTCL incidence within Georgia. [Table: see text]
Insulin resistance measured by the triglyceride-glucose index and risk of obesity-related cancers: An epidemiological investigation in more than 500,000 individuals.
Authors: Fritz Josef , Bjorge Tone , Nagel Gabriele , Concin Hans , Manjer Jonas , Häggström Christel , Stattin Pär , Stocks Tanja , Ulmer Hanno 
Published: May 2019

1552 Background: The role of insulin resistance as a mediator in the association of body mass index (BMI) with site-specific cancer risk has, to our knowledge, never been systematically quantified. We aimed to determine to what extent insulin resistance measured as the logarithmized triglyceride glucose product (TyG index) mediates the effect of BMI on risk of obesity-related cancers. Methods: A total of 510,471 individuals from six European cohorts with a mean age of 43.1 years were included in the study. We fitted Cox models, adjusted for relevant confounders, to investigate associations of TyG index with ten common obesity-related cancer sites, and quantified the proportion of the effect of BMI mediated through TyG index. Results: During a median follow-up of 17.2 years, 16 052 individuals developed obesity-related cancers. TyG index was associated with the risk of cancers of the kidney (hazard ratio (HR) per one standard deviation increase 1.13, 95% confidence interval: 1.07-1.20), liver (1.13, 1.04-1.23), pancreas (1.12, 1.06-1.19), colon (1.07, 1.03-1.10), and rectum (1.09, 1.04-1.14). Substantial proportions of the effect of BMI were mediated by TyG index for cancers of the pancreas (42%), rectum (34%), and colon (20%); smaller proportions for kidney (15%) and liver (11%); none for endometrium, ovary and breast (postmenopausal). Conclusions: In this pooled cohort study including more than 500,000 individuals, insulin resistance measured as the logarithmized triglyceride glucose product significantly mediated the effect of overweight and obesity on risk of cancers of the kidney, liver, pancreas, colon, and rectum. In contrast, insulin resistance did not mediate the risk for cancers of the endometrium, ovary and breast. Our results confirm a promoting role of insulin resistance in the pathogenesis of gastrointestinal cancers. Although often claimed, insulin resistance does not appear to connect excess body weight with cancers of the female reproductive organs.