bluuebunny/crossref_metadata_2025_split huggingface dataset:
Screening for antineoplastic ionic liquids by targeting RLIP76.
Authors: Khan Muhammad Saad , Hardwicke Fred L. , Igid Henry Palangdao , Kaleem Hassan , Awasthi Sanjay , Armstrong Daniel 
Published: September 2018

e13033 Background: RLIP76 is a stress-responsive multispecific transporter which functions as an anti-apoptotic protein in cancer cells. The targeting of RLIP76 by antibodies, antisense, or siRNA modalities causes complete regression of cancers such as melanoma, colon cancer and lung cancer. We carried out studies to determine whether the ATPase activity of purified recombinant human RLIP76 protein (encoded by RALBP1, chromosome 18p11.22) can be used to screen for novel ionic liquid compounds with antineoplastic activity. Methods: A series of ionic liquid compounds were tested for their ability to inhibit or activate the ATPase activity and doxorubicin transport activity of purified recombinant human RLIP76. The growth inhibitory effects of these compounds were monitored in human non-small cell lung cancer cell line NCI H358, with human aorta vascular smooth muscle cells serving as non-malignant controls. Results: ATPase activation correlated with doxorubicin transport inhibition. More importantly, the antineoplastic activity towards lung cancer cells was also correlated with degree of ATPase activation or transport inhibition. Cytotoxicity towards the non-neoplastic cell line was 1-2 orders of magnitude less than observed for the lung cancer cells, a characteristic of other agents that target RLIP76. The predicted antineoplastic effect was confirmed in H358 xenografts in nude mice. Conclusions: These studies indicate the potential utility of screening for antineoplastic agents using recombinant RLIP76 and also demonstrate antineoplastic activity of a novel ionic liquid compound.
Implementing decision support for breast cancer chemoprevention in primary care.
Authors: Telfort Jersen , Trivedi Meghna S. , Yi Hae Seung , Colbeth Hilary , Vanegas Alejandro , Vargas Jennifer , Sandoval Rossy , Wood Jeffrey , Dimond Jill , Finkelstein Joseph , Kukafka Rita , Crew Katherine D 
Published: September 2018

e13038 Background: Breast cancer risk assessment and chemoprevention with anti-estrogens among high-risk women are underutilized. We developed web-based decision support tools for high-risk women, RealRisks, and their primary care providers (PCPs), BNAV, which are integrated into clinic workflow. Methods: We conducted a pilot study in 50 women who were found to have a 5-year risk of invasive breast cancer ≥1.67% according to the Gail model during screening mammography. RealRisks includes modules on breast cancer risk and chemoprevention, as well as interactive games to communicate risk and preference elicitation for chemoprevention. A tailored patient and provider action plan is generated summarizing their breast cancer risk profile. Before and after interacting with RealRisks, participants completed validated questionnaires on breast cancer and chemoprevention knowledge and chemoprevention intention. Prior to their next clinic visit, their PCPs were given access to the BNAV reference toolbox. High-risk referrals and chemoprevention uptake were assessed by medical chart review. Paired t-tests and chi-square tests were used to analyze continuous and categorical variables pre/post-intervention, respectively. Results: From Mar to Aug 2016, 50 high-risk women were enrolled and 40 were evaluable. Median age 64.5 years (range, 49-72); white/black/Hispanic (%): 37.5/25/37.5; 35% had adequate health literacy; median 5-year breast cancer risk was 2.2% (range, 1.7-3.9). Before and after interacting with RealRisks, we observed an increase in adequate breast cancer knowledge (60% vs. 84%, p = .01) and chemoprevention knowledge (5% vs. 25%, p < .01). After viewing RealRisks, 30% of women were interested in taking an anti-estrogen for chemoprevention, 33% not interested, and 37% unsure. Thus far, only 2 were referred for high-risk consultations and no high-risk women initiated chemoprevention. Conclusions: Despite increased interest in chemoprevention after exposure to RealRisks, additional barriers to chemoprevention uptake exist, including competing comorbidities and time constraints during the clinical encounter. Targeting younger women with higher breast cancer risk may increase chemoprevention uptake. Clinical trial information: NCT02954900.
Greenville health system (GHS) experience with risk reduction endocrine therapy for women diagnosed with breast lobular carcinoma in situ (LCIS).
Authors: O'Neal Richard , Cornett Wendy R. , Jones Yonge R , Stewart Morgan , Franco Regina A. , Perkins Leann , O'Rourke Mark Allen 
Published: September 2018

e13041 Background: LCIS is associated with a 1% annual risk of developing invasive breast cancer, twice that of the general population. Endocrine therapy for chemoprevention has been shown to decrease this risk by 56% in women with LCIS. Barriers include failure to offer endocrine therapy and failure to tolerate it. This study examined a population of women with LCIS and their experience with endocrine therapy for breast cancer risk reduction. Methods: 337 patients with LCIS from 2010-2015 at the GHS were retrospectively identified through electronic health record review. Median age was 55.5 years; 303 underwent breast-conserving surgery and 34 mastectomy. Chart review assessed the documented recommendations for endocrine therapy, duration of adherence, and presence of side effects. Results: Endocrine therapy was prescribed in 155 (46%), refused in 33 (10%), and not recommended in 120 (36%). Of the 146 women who were started on endocrine therapy for risk reduction and followed for six months, 75% adhered to the endocrine therapy. Of the 94 followed for 2 years, 71% adhered. The rate of documented side effects was 14% and was the most commonly cited reason for discontinuation (78%). Conclusions: The number of women with LCIS that were not prescribed endocrine therapy in the absence of absolute contraindications was substantial (36%). Under documentation in the medical record may account for a portion of this. The rate of side effects of those started on endocrine therapy (14%) is lower than expected, although this may represent underreporting. With a low refusal rate (10%) and a high adherence rates (75% at 6 months and 71% at 2 years) in the treated population, improving the number of women with LCIS that are offered endocrine therapy has considerable potential for reducing breast cancer risk. Controlling side effects can increase the benefit further.
Examining screening behaviors at a high-risk ovarian cancer clinic.
Authors: Lynam-Scherr Courtney , Hope Kisha T , Helenowski Irene B. , Kocherginsky Masha , Keene Melissa , Strohl Anna Everett , Marshall-Fricker Charlotte , Guo Xiaoyue Mona , Shahabi Shohreh , Shulman Lee P 
Published: September 2018

e13047 Background: Women with deleterious BRCA1/2mutations have a significantly increased lifetime risk to develop ovarian cancer. Prophylactic surgery can significantly reduce ovarian cancer risk. The Northwestern Ovarian Cancer Early Detection and Prevention Program (NOCEDPP) was established to monitor this high-risk population prior to risk-reducing surgery. For such patients, providers in the NOCEDPP recommend screening with CA-125 and transvaginal ultrasound (TVUS) biannually. The aim of this study was to examine screening rates of women who have not had surgery but attend the NOCEDPP. Methods: We reviewed electronic health records of 1,662 women who attended the NOCEDPP clinic between October 2005 – October 2015. Demographic and clinical characteristics and utilization of screening were analyzed retrospectively using descriptive statistics and Kruskal-Wallis H-tests to examine differences in screening rates by age, race, ethnicity and insurance type. Results: Of the 1,662 women initially identified, 385 had a known BRCA mutation, 303 had an appointment with at least 6 months between first and last procedure – the sample included in the final analysis. Compared with women ages 35-45 (median = 1.91) and 45+ (median = 1.18), women ages 20-35 attended the most screenings per year (median = 2.12) p = 0.001, a rate consistent with biannual recommendations. There were no significant differences in screening rate by race, ethnicity, or insurance coverage. Conclusions: Despite changes in national guidelines, providers in our high-risk clinic continue to recommend CA-125 and TVUS biannually. Our preliminary data indicates patients’ attendance is uninfluenced by race, ethnicity, or insurance coverage. Further exploration of the impact of age is warranted. Implication of findings indicate a high-risk clinic may positively impact screening behaviors above and beyond factors typically associated with non-adherence.
Evaluating pulmonary nodules to detect lung cancer: Does Fleishner criteria really work?
Authors: Azharuddin Muhammad , Malik Aamir , Adamo Noor , Livornese Douglas S 
Published: September 2018

e13053 Background: The Fleishner Society recommends interval computed tomography (CT) follow-up for managing incidental small pulmonary nodules detected in CT scans. This study evaluates the clinical application of 2013 Fleishner criteria using a large cohort of patients at high risk for lung cancer with low-dose CT screening. Methods: During 2012-2016, a retrospective study of 176 patients was reviewed for incidental lung nodules. Patient eligibility included: men and women aged 55-74; 30 pack-year smoking history who quit in the last 15 years; no cancer history in the last 5 years; and no previous CT chest scan done. Follow-up and management was calculated using the Fleishner criteria. Nodules were classified based on several features including size and shape. Nodule characteristics were tabulated and analyzed. Results: Out of 176 patients, 117 had nodules and a total of 210 nodules were detected. Table 1 categorizes all nodule features including Fleishner Criteria. Of the entire cohort, two patients (1.1%) showed malignancy: one part-solid nodule of 10.2mm, and one multiple subsolid groundglass nodule (GGN) of 20.1mm. Twenty-one patients (17.9%) had undergone unnecessary follow-up CT scans, including those with solid nodules, and solitary pure GGNs. Conclusions: This study emphasizes the need to revise the Fleishner guidelines to more accurately estimate the risk of malignancy, including minimizing over-diagnosis, unnecessary follow-up CTs, and invasive procedures for benign pulmonary nodules. Further analysis of lung cancer contributory factors is also required. [Table: see text]
Genomic features of normal tissues from prophylactic surgery in BRCA1/2 mutation carriers.
Authors: Kotoula Vassiliki , Demiri Efterpi , Fostira Florentia , Vrettou Eleni , Charalambous Elpida , Tikas Ioannis , Papazisis Konstantinos , Zaramboukas Thomas , Asimaki-Vlachopoulou Anthoula , Miliaras Spyros , Fountzilas Elena , Ananiadis Ananias , Chrisafi Sofia , Poulios Christos , Natsiopoulos Ioannis , Tsiftsoglou Aris , Fountzilas George 
Published: September 2018

e13055 Background: Genomic alterations in normal tissues from pathogenic germline BRCA1/2 mutation (mut) carriers are as yet poorly described. We investigated the genomic status of normal breast (NB) and hystero-salpingo-oophorectomy (GYN) tissues removed upon prophylactic surgery in a real-life cohort of BRCA1/2 carriers. Methods: By using targeted NGS we examined the mut status of 220 samples (39 peripheral blood and 181 paraffin tissue) from 53 BRCA1/2 carriers who underwent prophylactic surgery, 42 with and 11 without prior cancer manifestation (PCM). We compared germline BRCA1/2 mut status with tumor, NB and GYN mut status. Results: Eight patients carried germline BRCA2 and 45 BRCA1 mut. Somatic mut were most frequent in BRCA2 (28%), BRCA1 (17%), TP53 (7%) among 136 NB and GYN samples; and, in TP53 (49%; p < 0.001) and BRCA1 (38%; p = 0.039) among 45 tumor samples. Among all tissue types, the 85 NB had the lowest mut load (p = 0.001). In NB and GYN, mut load was higher in BRCA1 vs. BRCA2 carriers (p = 0.027) and in those with BRCA1 substitutions/indels vs. exon deleting and skipping mut (p < 0.001). In tumors, only germline BRCA1 substitutions/indels were associated with higher mut load (p = 0.014). Preservation of germline mut in tissues was assessable in 84 samples from 26 patients. The germline mut was lost in 8 tumor and NB samples from 6 patients (23%) with PCM. Somatic deleterious mut in the BRCA1 BRCT-domain emerged in two such cases; the rest had combinations of TP53, MRE11A and NF1 mut. GYN samples from these patients retained the germline mut and presented the highest mut load among all examined samples (p < 0.001). Conclusions: Somatic mut in normal tissues from BRCA1/2 carriers are affected by the inherited mutated gene and by the type of the germline mut concerning BRCA1. Germline BRCA1 mut may be substituted by somatic mut in tumor and normal tissues, in an organ specific manner. Mutagenesis in tumors and normal tissues appear to be driven by different pathways. Our findings shed new light on the biological impact of BRCA1/2 mut in tissues.
Genetic ancestry in normal breast tissue donors from the Susan G. Komen tissue bank at the IU Simon Cancer Center (KTB).
Authors: Marino Natascia , McCarty Julia , Jiang Guanglong , Johnson Mariah L , Mahin Teresa , Scherer Nicholas , Storniolo Anna Maria 
Published: September 2018

e13065 Background: When studying complex diseases with a heritable component, such as breast cancer, chances of finding disease susceptibility genes can be increased by accounting for genetic ancestry within the population investigated. The limitation in using self-reported race to reveal population genetic substructure has been extensively reported. Therefore, we employed a panel of genetic polymorphisms, or Ancestry Informative Markers (AIMs), to genetically determine the racial and ethnic background of the tissue donors in the KTB, the only existing biobank of breast tissue cores taken from healthy women. Methods: 4112 women donated breast tissue between 2006 and 2016, and also provided race and ethnicity information. We used a panel of 41 AIMs to estimate genetic ancestry and to maximize the difference between European/ Middle East (Caucasian, C), East Asia and Central/South Asia (Asian), African, and Hispanic populations. We employed the Bayesian Markov chain Monte Carlo (MCMC) method implemented in the program STRUCTURE 2.2. A reference set was obtained from the Human Genome Diversity Project. Results: In women self-identified as Black/African American (AA),White and Asian, the assigned genetic ancestry proportions were 93.8% African, 95% C and 96.6% Asian respectively, while the racial composition among the 318 self-identified Hispanics (of which only 178 were confirmed by the genetic ancestry) was 45.3% C, 5.3% African, and 14.7% Asian. Interestingly, 46.9% of the Asian population failed to report the racial background. This percentage was lower for C (1.3% ) and AA (0.5%). Women with African ancestry were younger (≤35 yrs) at the time of donation (24%), as compared to the C (32%) and Asian (33.7%) donors. The obesity rate (BMI > 30) is higher in the AA (60.6%) and C (36.6%), as compared to the Asian population (26.6%). Conclusions: A well-characterized genetic background of the normal breast tissue donors in the KTB will allow a more accurate examination of the association of the genetic ancestry with breast cancer events or risk factors with the ultimate goal of more fully understanding breast cancer racial disparities and their possible role in the risks for and outcomes of breast cancer.
Cancer events in Belgian nursing home residents (NHR): An EORTC prospective cohort study.
Authors: Wildiers Hans , Elseviers Monique , Mauer Murielle E. , de Wolf Jonas , Bastiaens Edith , Hatse Sigrid , Hamaker Marije , Buntinx Frank , de Lepeleire Jan , Uytterschaut Geert , Tryfonidis Konstantinos , Janssen-Heijnen Maryska 
Published: September 2018

e13066 Background: A large prospective cohort study was designed to describe cancer events, referral patterns, anticancer treatments and outcome in NHR. Methods: The study was set up in 39 nursing homes from the Armonea network in Belgium, covering 4262 nursing home beds. Cancer events were defined as a new cancer event (new cancer or progressive disease of a previously known cancer) where a diagnostic/treatment decision had to be taken; and patients with strong clinical suspicion (physician’s judgement) of a new cancer event, but where the decision was made not to take further diagnostic/therapeutic steps. Cancer events in NHR were collected during a 1y-period in these 39 nursing homes. After training, each site’s local staff identified patients with cancer events in collaboration with the treating general practitioner (GP). NHR were included after informed consent, and relevant data, including a questionnaire for the GP at baseline, were recorded at least every 3 months up to 2 years. Results: The study was open from 3-2015 till 3-2016 in 37 nursing homes (and 2 pilot nursing homes started and stopped 6 months earlier). In only 9 NHR (median age 87y, range 72-92), cancer events were recorded during this period (incidence rate = 222/100,000 NHR per year). The 9 tumor cases were: one strong clinical suspicion of new prostate cancer, and one undefined cancer; a strong clinical suspicion of breast cancer progression; 3 newly diagnosed cancers (angiosarcoma of the breast, head and neck plus gingiva cancer, and one undefined) ; 3 cases with diagnosed progression of a previously known tumor (skin cancer, head and neck cancer plus skin cancer, bladder cancer). During follow-up, 6/9 NHR died, with a median overall survival of 5 Mo (range 2-16 Mo). Further details on diagnostic/therapeutic approach and outcome are pending. Conclusions: This study evaluated for the first time cancer events prospectively in a large nursing home population. Clinically relevant cancer events occur at a much lower frequency in NHR than expected from cancer incidence data in the general older population, supporting several previous retrospective observations that cancer events are much less frequent and problematic in very frail older persons than previously expected. Clinical trial information: NCT01910376.
Sex differences in cancer risk and survival.
Authors: Radkiewicz Cecilia , Johansson Anna , Dickman Paul , Lambe Mats , Edgren Gustaf 
Published: September 2018

e13074 Background: The ongoing global cancer increase poses immense challenges for cancer care. Few comprehensive analyses of sex differences in cancer risk and survival based on robust data have been conducted. Methods: We performed a large cohort study using nationwide Swedish Cancer Register data for years 1970-2014, including all adult incident, non-breast, non-genital cancer cases (504,379 male, 368,018 female). To assess the strength of association between sex and cancer we estimated male-to-female incidence rate ratios†. Relative survival models were used to quantify differences in survival and were expressed as excess mortality ratios*. We applied Poisson regression and adjusted for age and calendar year in both. Results: Men were at significantly increased risk for 34 of 39 sites, and had significantly poorer prognosis for 27 of 39, compared to increased risk for 5 of 39 sites and poorer survival for 2 of 39, in women. Incidence rate ratios in male predominant sites ranged from 1.05; 95% CI, 1.03-1.08 (lung adenocarcinoma) to 8.00; 95% CI, 7.50-8.53 (larynx), corresponding to 0.38; 95% CI, 0.36-0.39 (thyroid well-differentiated) to 0.69; 95% CI, 0.63-0.75 (thyroid anaplastic) in female predominant sites. In sites with poorer survival in men, excess mortality ratios ranged from 1.07; 95% CI, 1.03-1.10 (colon) to 2.08; 95% CI, 1.53-2.84 (well-differentiated thyroid). Conclusions: Male sex is an independent risk factor and associated with poorer survival for a large majority of cancer sites. The excess risk in men remains elevated over time for most sites. Identifying and eliminating factors driving sex differences may reduce global cancer burden considerably. [Table: see text]
Choriocarcinoma in males: A Surveillance, Epidemiology, and End Results (SEER) analysis.
Authors: Howard Alexander , Drury Lane , Han Yimei , Ersek Jennifer Lynne , Symanowski James Thomas , Riggs Stephen Boyd , Feldman Rebecca , Kim Edward S. 
Published: September 2018

e13079 Background: Choriocarcinoma (CCA) is a rare tumor. In men, the main site is testis. Pure CCA composes < 0.3% of testicular germ cell tumors. Other sites may represent metastatic disease (dz) or a non-testicular primary CCA. Surgery (S) is the preferred treatment as diagnosis prior to resection is difficult. We analyzed SEER data to determine demographic/clinical characteristics of male CCA patients (pts) and assess survival outcomes. Methods: Male pts with a confirmed diagnosis of CCA as their only primary tumor were included. Pts were grouped into cohorts by dz site (testis, other primary sites, all). S was defined as any type of surgery or no surgery. Stage was defined as local/regional or distant. Dz type was defined as pure or mixed. Overall survival (OS) and disease-specific survival (DSS) were analyzed with Cox proportional hazards (PH) models and Kaplan-Meier methods (5-yr landmark rates reported). Results: 1221 men were identified from 1988-2013. Median age = 28 (range 0-84). Other characteristics included: White (86.9%), mixed CCA (64.9%), local/regional (45.4%), S (78.7%) and testis (83.0%). For other primary site pts (17.0%), lung/mediastinum was most common (36.7%). Stage and S significantly impacted OS and DSS, regardless of dz site. For testis pts, OS (95% vs 56%; p < .001) and DSS (96% vs 61%; p < .001) were significantly better for pts with local/regional dz, as were OS (68% vs 27%; p = 0.032) and DSS (68% vs 29%; p = 0.042) for other primary site pts. Testis pts with S had significantly improved OS (83% vs 34%; p < .001) and DSS (85% vs 40%; p < .001), as did other primary site pts with S (OS: 54% vs. 23%; p = 0.004 and DSS: 62% vs. 34%; p = 0.002). OS for all pts was analyzed with a multivariable Cox PH model, including age, marital status, dz site and type, stage, and S. Testis pts had a reduced risk of death compared to other primary site pts (HR 0.66; 95% CI 0.47-0.92). Pure CCA pts had a 61% increased risk of death compared to mixed CCA pts (HR 1.61; 95% CI 1.24-2.08). S pts had a 48% reduced risk of death compared to pts without S (HR 0.52; 95% CI 0.40-0.67). Conclusions: Pure CCA and non-testicular primary pts have poorer outcomes. S is an important component to survival in men with CCA. This is the first descriptive analysis of male CCA utilizing SEER.