bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B63: ESR1 variants are not associated with breast cancer in African American women
Authors: Ochs-Balcom Heather M. , Sucheston Lara , Liu Song , Hutter Carolyn , Young Alicia , Peters Ulrike , Chlebowski Rowan , Wactawski-Wende Jean 
Published: June 2012

Abstract
The estrogen receptor alpha (ESR1) gene is a candidate gene for breast cancer due to the ligand-activated transcription factor it encodes. The Breast Cancer Association Consortium (BCAC) identified an association of haplotype tagging SNPs in intron 4 of ESR1 and breast cancer risk in 21 European studies that include 53,994 subjects. We examined whether this association replicated in an African American sample from the Women's Health Initiative Single Nucleotide Polymorphism (SNP) Health Association Resource (WHI SHARe). Using this sample of 7800 postmenopausal women, of whom 316 have incident invasive breast cancer, we measured the genetic association of variants in ESR1 and breast cancer risk using Cox proportional hazards models adjusted for age, region, and principal components 1–4 taken from cluster analyses of genomic ancestry. All samples were genotyped on the Affymetrix 6.0 platform, and imputed with HapMap 2 populations (CEU and YRI) as reference. With regard to ER status, 68% of women in our sample (with known ER status) have ER-positive tumors. The most significant BCAC SNP, rs3020314, was not statistically significant in our study (HR: 1.09, 95% CI: 0.91–1.30) and we found no association between any of the other 130 SNPs tested in the ESR1 locus after Bonferroni correction. While our results for rs3020314 are in the same direction than the reported BCAC association it should be noted that the minor alleles differ by race; the C allele is more common in African Americans and the T allele is more common in BCAC (and the HapMap CEU sample). In our study, the minor (T) allele frequencies for rs3020314 are 0.295 for cases and 0.313 for controls. This lack of replication of the findings in intron 4 and the entire ESR1 locus suggests that ESR1 variants may not be associated with breast cancer in African American women. This may be due to a number of factors including linkage disequilibrium structure differences across races, small sample size and reduced power of the WHI sample, or may reflect disparity in tumor type, as African American women have a higher frequency of tumors that are estrogen receptor-negative.
Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):B63.
Abstract B82: Health disparities of esophageal cancer by histological type in Puerto Rico: 2000–2004
Authors: González Lorena , Magno Priscilla , Ortiz Ana P. , Ortiz-Ortiz Karen , Nogueras Graciela , Suárez Erick 
Published: June 2012

Abstract
Background: Esophageal cancer (EC) has been ranked as the 8th most incident cancer and the 6th most common cause of death from cancer in the world. Hence, the primary aim of this study was to assess the age-standardized incidence (ASI) rates by histology type of EC in Puerto Rico (PR) and contrast these statistics with those of US Hispanics (USH), non-Hispanic Whites (NHW), and non-Hispanic Blacks (NHB) in the US.
Methods: We applied the direct method to compute the ASI rates for EC (per 100,000 persons) by histology type during 2000 to 2004, using the World Standard Population. The age specific relative risks (RR) and the overall comparison of two standardized rates (SRR) were estimated with 95% confidence intervals to determine relative differences among the study groups, during the same period of time, using the Poisson regression model and PR as reference.
Results: Overall, in PR during the years 2000–2004, the ASI rates (x 100,000 persons) for all EC were 16.8; among male 36.1 and among females 11.6. The risk of developing any histology type of EC in PR was higher than NHW for both sexes (SRRmales: 1.14, 95%CI: 1.02–1.28; SRRfemales: 1.27, 95%CI: 1.06–1.51) and USH (SRRmales: 1.45, 95%CI: 1.21–1.76; SRRfemales: 2.39, 95%CI: 1.74–3.35). PR also showed 2 to 3 times the risks of developing esophageal squamous cell carcinomas (ESCC) compared to NHW and USH for both sexes (p&lt;0.05); only a risk reduction was observed when Puerto Rican males were compared to NHB males (p&lt;0.05). Inversely, PR showed lower risks of developing esophageal adenocarcinomas (EAC) in comparison to NHW for both sexes (SRRmales: 0.29, 95%CI: 0.22–0.37; SRRfemales: 0.36, 95%CI: 0.21–0.55) and USH (SRRmales: 0.50, 95%CI: 0.35–0.70; SRRfemales: 0.71, 95%CI: 0.36–1.40).
Conclusions: Differences in EC incidence rates exist overall and by histology type among Puerto Ricans, NHW, NHB, and USH. Future research is warranted to elucidate the effect of the different risk factors and genetic predisposition for each histology type of EC in PR and among US racial/ethnic populations.
Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):B82.
Abstract B94: The effect of clinic on identifying predictors of HPV co-testing with Pap in routine cervical cancer screening
Authors: Phelan Darcy F. , Boitnott John K. , Clark Douglas P. , Dubay Lisa C. , Gravitt Patti E. 
Published: June 2012

Abstract
Background: Human papillomavirus (HPV) co-testing with Pap is recommended for cervical cancer screening among women ≥ 30 years. However, little has been reported regarding actual provider use of HPV co-testing with Pap in clinical practice.
Purpose: We sought to identify predictors of HPV co-testing with Pap among women ≥ 30 years by utilizing laboratory and administrative data from the Johns Hopkins Hospital Division of Cytopathology in Baltimore, MD.
Methods: We analyzed 51,027 Pap specimen records and 4,148 HPV test records among 30,272 women ≥ 30 years in 88 clinics from February 2004 to December 2007. The outcome was HPV co-testing with Pap among women ≥ 30 years, and covariates included patient race, age, insurance type, ZIP code median household income, and calendar year. We constructed population-average logistic regression models. These included robust standard error estimation for clinic clustering and, at times, a fixed-effects estimator for within-clinic effects. We also stratified our analyses to five individual clinics.
Results: The overall proportion of HPV co-testing with Pap was 8.1%. Notably, 12.8% of Pap specimens of black women received HPV co-testing compared to 5.2% for specimens of white women and 6.2% for those of women of other races (p&lt;0.01). Bivariate predictors of HPV co-testing with Pap among women ≥ 30 years included race, age, insurance type, ZIP code median household income, and calendar year. Most of these associations, however, could be explained by clinic-level differences in HPV co-testing. For example, the bivariate odds ratio for black race, OR 2.69 (95% CI 1.21–5.98), was modified to OR 0.92 (95% CI 0.82–1.03) by a fixed-effects estimator for clinic. Using five representative large clinics, clinic-stratified analyses did not support an independent association with HPV co-testing for race, insurance type, or ZIP code median household income, although an increase in HPV co-testing over time was observed in most clinics.
Conclusions: Under a population-average public health approach, the predictors of HPV co-testing with Pap varied between the pooled analyses and clinic stratified analyses. Using fixed-effects estimation to account for between-clinics effects in the pooled analyses provided further evidence for the substantial influence of clinics on the findings. This research suggests that the predictors of HPV co-testing with Pap among women ≥ 30 years likely lay at the provider and/or clinic level(s).
Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):B94.
Abstract ED04-03: Genetic variation among populations
Authors: Kidd Kenneth K. 
Published: June 2012

Abstract
Modern humans evolved in Africa and spread around the rest of the world only within the past 80 to 100 thousand years. During that process and subsequently allele frequency differences among the populations arose and those differences have great biomedical implications. The overall genetic pattern reflects the original expansion pathways out of Africa, but individual loci can vary greatly from that pattern. In contrast to the belief in distinct biological races, we see nearly continuous genetic variation across the globe among indigenous populations. While variation occurs, it is impossible to draw a line separating “races”. Examples of population variation in alleles relevant to cancer risk and therapeutic outcomes illustrate the global differences that do exist. Populations arising more recently with ancestry from geographically separated parts of the world have a mosaic pattern of ancestral DNA along their chromosomes such that an overall level of admixture is a poor predictor of the ancestral origins of alleles at any specified locus. These considerations become important in more personalized medicine.
Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):ED04-03.
Abstract PL04-04: Population impact: Using modeling to evaluate contributions of screening, treatment, and biology on disparities in breast cancer outcomes
Authors: Mandelblatt Jeanne 
Published: June 2012

Abstract
Purpose: U.S. Black women have higher breast cancer mortality rates than White women despite lower incidence. The disparity is growing and the reasons for this disparity remain uncertain. The aim of this study is to investigate how much of the mortality disparity can be attributed to racial differences in natural history, uptake of mammography screening and use of adjuvant therapy.
Methods: Two simulation models use common national race- and age-specific data for incidence, screening and treatment dissemination, stage distributions, survival and competing mortality from 1975 to 2010. Treatment effectiveness and mammography sensitivity are assumed to be the same for both races. We sequentially substituted Black parameters into the White model to identify parameters that drive the higher mortality for Black women in the current time period (2004–2006).
Results: Both models accurately reproduced observed breast cancer incidence, stage and tumor size distributions and breast cancer mortality for White women. The higher mortality for Black women could be attributed to differences in natural history parameters (26–44%), use of adjuvant therapy (11–19%) and uptake of mammography screening (7–8%), leaving 38–46% unexplained.
Conclusion: Black women appear to have benefited less from cancer control advances than White women, with a greater race-related gap in the use of adjuvant therapy than mammography screening. However, a greater portion of the disparity in breast cancer mortality appears to be due to differences in natural history and undetermined factors.
Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):PL04-04.
Abstract PL06-02: Patient navigation and timeliness of diagnostic evaluation: Results from the Patient Navigation Research Program
Authors: Freund Karen M. , Paskett Electra , Corle Donald , Snyder Frederick R. , Calhoun Elizabeth , Dudley Donald J. , Murray David M. , Patierno Steven , Roetzheim Richard G. , Warren-Mears Victoria , Whitley Elizabeth , Winters Paul C. 
Published: June 2012

Abstract
Background: Patient navigation has been proposed as a means to reduce cancer health disparities, through the addition of a trained navigator to the health care team. Patient navigators help patients to identify barriers to receiving needed care, and to develop individually targeted plans to overcome these barriers. The Patient Navigation Research Program is a nine-site program to evaluate the benefit of patient navigation among underserved populations from diverse socioeconomic and geographic locations within the United States.
Methods: Patients with breast, cervical, colorectal or prostate screening abnormalities were eligible for enrollment. The primary outcome was time to diagnostic resolution of the screening abnormality, assessed dichotomously as resolved or not within 365 days, and analyzed using survival curves and Cox proportional hazards models of time to resolution by 12 months. Due to the differing study designs at the 9 sites (RCT, Group randomized, and non randomized group allocation) we calculated an effect size for each cancer type for each site, and utilized a meta-analysis to assess an overall effect size. Models were adjusted for age, race, insurance and marital status.
Results: There were 10,513 subjects (5,055 Navigated and 5,458 Non-navigated) recruited from the 9 sites, 64% with breast cancer screening abnormalities. The study population was diverse with 74% from minority groups (32% African American, 39% Latino, 4% other), and low income with 17% Medicaid insured, and 32% with no insurance. In the control population, 62% to 95% of the participants did not reach diagnostic resolution after their abnormal screening result within 12 months. Those in the navigation arm were more likely to reach resolution after an abnormal test in 13 of the 15 cancer sites, (89 to 99% resolved). Of the 15 hazard rate ratios, 11 showed a statistically significant positive effect of the navigation intervention, 3 others showed a non statistically significant benefit of navigation, and 1 showed a negative effect of navigation on time to diagnostic resolution, (effect sizes ranging from an adjusted HR of 0.38 to 3.94, with a higher HR favoring the navigation arm).
Implications: Compared to non-navigated subjects, participants with an abnormal cancer screening test who were allocated to receive a patient navigation intervention were more likely to receive timely diagnostic resolution of their abnormal screening test. Patient navigation for vulnerable populations may be beneficial in reducing cancer disparities.
Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):PL06-02.
Abstract PL06-05: The cost effectiveness of patient navigation
Authors: Bensink Mark E. , Ramsey Scott D. , Raich Peter C. , Seiber Eric , Warren-Mears Victoria , Mandelblatt Jeanne S. , Battaglia Tracy , Everhart Rachel M. , Fiscella Kevin , Freund Karen , Hurd Thelma C. , McKoy June M. , Paskett Electra D. , Patierno Steven R. 
Published: June 2012

Abstract
Navigation requires investment, investment in training and establishing navigators and supporting them to provide navigation to patients. The cost-effectiveness of patient navigation weighs the investment required against the effect produced. The result is a measure of the value provided by navigation. The aim of this presentation is to present data from the PNRP experience estimating the investment required to implement patient navigation and the resulting economic impact on diagnostic and treatment services, weighed against the effect of patient navigation on the PNRP intermediate outcomes of time to diagnosis, time to treatment, patient satisfaction and patient quality of life.
Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):PL06-05.
Abstract PR2: Warburg effect revisited: Glucose addiction in precancerous mammary epithelial cells in African American women
Authors: Ibarra-Drendall Catherine , Sistrunk Chris , Hoffman Abigail , Ford Ane , Seewaldt Victoria Louise 
Published: June 2012

Abstract
Background: Only 14% of African American women with triple-negative breast cancers will be alive at one year. Early detection is greatly needed. Here we aimed to investigate whether activation of biologic pathways that predict aggressive triple-negative breast cancers are also activated in atypia in high-risk African American women. Aggressive cancers are known to consume glucose avidly and produce lactic acid (rather than fully metabolize glucose via the Tricarboxylic Acid (TCA) cycle). This shift toward lactate production, even in the presence of adequate oxygen, is termed the Warburg effect. The Warburg effect is thought to be a late event in breast cancer, however, our studies in high-risk African American women provide evidence that the Warburg effect occurs during cancer initiation. This is an important observation as glucose-signaling can be readily targeted for breast cancer prevention with minimal toxicity. Here we investigated the role of the Warburg effect in breast cancer initiation in young high-risk African American women.
Methods and Results: Similar to fluorodeoxyglucose, 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG) is a fluorescent glucose analog that can be used to track glucose uptake and glycolysis. 2-NBDG spectroscopy provides a means to track glucose metabolism in live mammary epithelial cells from high-risk women. We used 2-NBDG spectroscopy to measure glucose uptake in ER-breast cancer and live atypical mammary epithelial cells from high-risk premenopausal women. We observe that both triple-negative breast cancer and a subset of atypia exhibits accumulation of 2-NBDG.
There is growing recognition that phosphoprotein signaling networks (rather than single genes) play a key role in breast cancer initiation and progression. Our team used Reverse Phase Proteomic Microarray (RPPM) profiling to test for activation of phosphoprotein signaling networks in atypical RPFNA cytology from high-risk premenopausal women in our cohort. RPFNA were obtained from two independent sets of 39 and 38 high-risk premenopausal women; 45% of these women were African American. The signaling network most highly expressed in precancerous cells contained activated signaling proteins associated with the Warburg effect (AKT/mTOR/PI3K), insulin signaling (pACC, IRS1) and epithelial to mesenchymal transition (EMT) IL6/Stat3/vimentin.
Conclusions: This is the first evidence that abnormal glucose uptake and the Warburg effect occurs during breast cancer initiation in high-risk African American premenopausal women. These studies demonstrate our ability to identify abnormal glucose and activated signaling networks associated with the Warburg effect in atypical mammary cells from high-risk African American women and provide an important target for breast cancer early detection and prevention.
Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):PR2.
Abstract A108: A phase I and pharmalogical study of the broad-spectrum tyrosine kinase inhibitor JNJ-26483327, administered to subjects with advanced or refractory solid tumors
Authors: Konings Inge R. , de Jonge Maja J. , Burger Herman , van der Gaast Ate , van Bijsterveld Ludy EC , Winkler Hans , Hellemans Peter , Eskens Ferry A. 
Published: June 2012

Abstract
Background: JNJ-26483327 is a potent reversible multi-targeted tyrosine kinase inhibitor. Tyrosine kinases of Epidermal Growth Factor Receptor (EGFR), Her2, Her4, RET receptor, Vascular Epidermal Growth Factor Receptor (VEGFR)-3, and Src family (Lyn, Fyn, Yes) are inhibited at low nanomolar concentrations.
Methods: Objectives were to (1) determine safety, maximum tolerated dose (MTD) and dose-limiting toxicity (DLT), (2) characterize the pharmacokinetic (PK) profile, (3) explore preliminary evidence of antitumor activity, and (4) explore pharmacodynamic (PD) effects in skin biopsies and blood.
Results: 19 patients, 16 M/3F, median age 61 yrs (47-74) received JNJ-26483327 twice daily (BID) continuously at 100 mg (n=1), 200 mg (n=1), 400 mg (n=1), 800 mg (n=3), 1200 mg (n=3), 1500 mg (n=6) and 2100 mg (n=4). JNJ-26483327 was administered as oral solution (dose ≤ 1200 mg) or capsules (dose ≥ 1500 mg, 300 mg capsule). Skin biopsies were taken at days 0 and 28. At 2100 mg DLT consisted of a combination of grade 3 anorexia and fatigue in one patient, and due to substantial difficulty in intake in most patients, pill load at 2100 mg was dose limiting. JNJ-26483327 was well tolerated up to 1500 mg BID, with most common reported toxicities being nausea, vomiting, diarrhea, fatigue, skin rash. Plasma concentrations of JNJ-26483327 rapidly increased till about 3–4h post dose. PK showed significant inter-individual variability, but no marked deviation in dose-proportionality was observed up to 1500 mg BID. At 1500 mg BID, steady state plasma concentrations were 2–6 µg/l and AUCs 13–53 µg.h/ml and were in the active range as observed in xenograft mouse models. PD evaluation failed to show a substantial effect on expression of Ki-67, p27kip1, pMAPK, pAKT, and EGFR in paired skin biopsies. Serum levels of sVEGFR-2, VEGF-C and VEGF-D remained unchanged. No antitumor activity was observed in this study.
Conclusion: The recommended dose of JNJ-26483327 is 1500 mg BID. JNJ-26483327 shows a predictable pharmacokinetic profile. Additional PD research is planned to demonstrate biological activity.
Citation Information: Mol Cancer Ther 2009;8(12 Suppl):A108.
Abstract A126: Analysis of excision repair cross complementing group 1 (ERCC1) expression in squamous cell carcinoma of the head and neck (SCCHN)
Authors: Mehra Ranee , Cai Qi K. , Zhu Fang , Godwin Andrew , Burtness Barbara 
Published: June 2012

Abstract
Introduction: ERCC1 is a key enzyme in the nucleotide excision repair pathway and increased expression of ERCC1 is associated with cisplatin resistance in some cancers. Given the widespread use of platinum therapy for the treatment of SCCHN, we characterized the range of ERCC1 expression in SCCHN specimens using an immunofluorescence-based assay (automated quantitative analysis-tissue microarray [AQUA-TMA]). There is currently inadequate data regarding the range of ERCC1 expression in SCCHN, and how ERCC1 levels correlates with treatment outcomes, ERCC1 has been studied in SCCHN by standard immunohistochemistry, however, this method is limited by variability of techniques and subjectivity of interpretation, Therefore, there is a need for a highly quantitative technique which can be accomplished on formalin fixed paraffin embedded tissue and small samples, Our goal is to develop a reproducible assay that can eventually be incorporated into standard patient care practice.
Methods: Tissue microarrays containing head and neck squamous cell carcinoma samples obtained from patients treated at Fox Chase Cancer Center from 1999–2006 were constructed. Slides were stained by a modified indirect immunofluorescence method. Sections were incubated with ERCC1 antibody (8F1, Lab Vision) and wide-spectrum screening rabbit cytokeratin antibody (Dako Z0622). Prolong Gold mounting medium (P36931; Molecular Probes) containing 4,6-Diamidino-2-phenylindole (DAPI) was used to define tissue nuclei. A binary image (tumor mask) was created from the cytokeratin image of each histospot. ERCC1 levels were measured using fluorescent immunohistochemistry on the HistoRx PM-2000 image analysis platform and the data analyzed using AQUA algorithms. The in situ biomarker profiling system generated quantitative measurements of patient protein levels based on AQUA scores derived from fluorescent output of labeled markers. Both nuclear and non-nuclear (i.e., non-membrane/cytoplasmic) ERCC1 expression was measured
Results: 41 SCCHN specimens (24 oral cavity, 7 oropharynx, 5 glottic tumors, 3 unknown primary, 2 other) were analyzed. There were 25 males and 16 females and age at diagnosis ranged from 25 to 80 years (mean 64). The majority of patients were treated primarily by surgery. The range of AQUA scores was 33.66 to 1696.39 (mean 501.78, stnd deviation 284). The 25th percentile was 337.35, and the 75th percentile was 639.37. ERCC1 was predominantly nuclear (i.e., non-membrane/cytoplasmic) in the SCCHN tissue samples.
Conclusions: 1) It is feasible to determine a quantitative value of ERCC1 expression with AQUA. 2) There is a wide range of ERCC1 expression in SCCHN. 3) ERCC1 is predominantly localized to the nuclear compartment. 4) Ongoing work is being done to correlate ERCC1 levels with clinical features, sensitivity to platinum therapy, and survival.
Citation Information: Mol Cancer Ther 2009;8(12 Suppl):A126.