bluuebunny/crossref_metadata_2025_split huggingface dataset:
Knowledge outcomes in a randomized trial of telephone vs. in-person disclosure of genetic testing: The COGENT study.
Authors: Beri Nina , Patrick-Miller Linda J. , Egleston Brian L. , Olopade Olufunmilayo I. , Hall Michael J. , Daly Mary Beryl , Fleisher Linda , Grana Generosa , Ganschow Pamela , Fetzer Dominique , Domchek Susan M. , Bradbury Angela R. ,   The COGENT Research Team
Published: September 2018

1534 Background: Telephone disclosure (TD) of genetic testing is non-inferior to in-person disclosure (IPD) for most outcomes but did not meet non-inferiority for knowledge change. We sought to understand which concepts patients don’t understand and factors associated with lower knowledge. Methods: Patients were recruited to a multi-center, randomized trial (NCT01736345) comparing TD to IPD of genetic test results. 819 patients were randomized (IPD = 418; TD = 401); 165 declined randomization and requested IPD. Knowledge was assessed after pre-test counseling (V1) and test disclosure (V2). Results: There were no significant differences in genetic or multi-gene (MG) knowledge between disclosure groups after V1 and V2. On average, patients answered 73% (SD 1.19) of genetic knowledge and 57% (SD 1.78) of mg knowledge items correctly.After V1, most understood implications of a positive result (87%), that results are not deterministic (84%) and risks for their children (91%). Understanding of uninformative negative, true negative and variant of uncertain significance (VUS) results was lower (post-V1: 33%, 65%, 29%; post-V2 : 37%, 65%, 25%). In multivariable analyses, lower genetic knowledge after V1 was associated with study site, being older (p < 0.01), single (p < 0.01), non-white (p < 0.01), not Ashkenazi Jewish (p = 0.01), and not having a mutation in the family (p = 0.03), having more relatives with cancer (p < 0.01) and not graduating college (p < 0.01). Lower mg knowledge after V1 was associated with site and being non-white (p = 0.01). Lower genetic knowledge after V2 was not associated with disclosure method but associated with study site, being older (p < 0.01), not graduating college (p < 0.01) and being non-white (p < 0.01). Lower mg knowledge after V2 was only associated with not graduating college (p = 0.02). Conclusions: While there were no significant differences in genetic knowledge by disclosure method, understanding of several concepts (e.g. VUS and negative results) were lower regardless of arm. Several factors, including age, education and race/ethnicity were associated with lower knowledge. Interventions to improve genetic knowledge in real-world and diverse populations are needed. Clinical trial information: NCT07136345.
The scientific impact and value of large, NCI-sponsored randomized phase III cancer prevention trials.
Authors: Unger Joseph M. , Barlow William E. , Tangen Catherine M. , Ramsey Scott David , Thompson Ian Murchie , Klein Eric A. , LeBlanc Michael Leo , Blanke Charles David , Goodman Phyllis J. , Minasian Lori M. , Hershman Dawn L. 
Published: September 2018

1541 Background: The cooperative cancer research groups of the National Cancer Institute’s National Clinical Trials Network have a history of successful conduct of large randomized phase III trials of prevention for cancer. An important question for funding agencies is whether the conduct of large prevention trials provides strong scientific return on investment. Methods: We used study data from a single NCI-sponsored cooperative group (SWOG) over a 20-year period (1990-2009, inclusive). During this time, SWOG conducted two large prevention trials (the Prostate Cancer Prevention Trial and the Selenium and Vitamin E Cancer Prevention Trial) and numerous treatment trials. Scientific impact for prevention and treatment trials was examined using citation analysis. Average annual citation counts were compared using t-tests. Scientific impact was also assessed as a function of trial costs. Results: Twenty-six treatment trials with 16,391 patients and two prevention trials with 54,415 patients were examined. The mean annual citation rate for primary articles was higher for prevention trials compared to treatment trials (173.6 vs. 41.7, p = .003). For both primary and secondary article publications, mean annual citations for articles associated with prevention trials were also higher (557.2 vs. 67.6, p < .0001). Large prevention trials were estimated to provide 70% greater scientific impact on a cost-adjusted basis. Conclusions: Based on these criteria, the scientific impact of large phase III cancer prevention trials was very high in absolute terms and after accounting for trial costs. For appropriate scientific questions, large prevention trials provide a strong scientific return on investment for federal funding agencies.
Immune profiling of oral pre-malignant lesions (OPLs): An Erlotinib Prevention of Oral Cancer (EPOC) study biobank analysis.
Authors: William William Nassib , Uraoka Naohiro , Peng S. Andrew , Lee J. Jack , El-Naggar Adel K. , Parra Cuentas Edwin Roger , Rodriguez-Canales Jaime , Gillenwater Ann M. , Lin Heather Y. , Wistuba Ignacio Ivan , Myers Jeffrey , Gold Kathryn A. , Hwu Patrick , Heymach John , Papadimitrakopoulou Vassiliki , Lippman Scott Michael 
Published: September 2018

1545 Background: We previously demonstrated that high-risk loss of heterozygosity (LOH) profiles (i.e., 3p14/9p21 LOH) and EGFR gene copy number gain (CNG) in OPLs were associated with inferior oral cancer-free survival (OCFS) in patients enrolled in the randomized EPOC trial. Herein, we performed comprehensive immune profiling of OPLs and correlated the findings with molecular features and outcomes, using the prospectively collected and clinically annotated EPOC biobank. Methods: We evaluated OPL specimens by multiplex immunofluorescence using the Opal 7-color fIHC Kit and the Vectra multispectral microscope / inForm Cell Analysis software. Markers included AE1/AE3 pancytokeratins, PD-L1 (clone E1L3N), CD3, CD8, and CD68. Wilcoxon rank-sum and Fisher’s exact tests were used to assess the associations between binary markers and continuous and categorical variables, respectively. Cox model was used to investigate associations of markers with OCFS. Results: The cohort included 188 OPL patients with hyperkeratosis/hyperplasia (18%), mild/moderate (44%), or severe dysplasia (5%); 65% had high-risk LOH profiles. The 5-year OCFS was 72.3% (median follow-up of 50 months). PD-L1 expression in > 1% of epithelial cells occurred in 28% of OPLs. Intraepithelial CD3+, CD3+/CD8+, CD68+, and CD68+/PD-L1+ cells were detected in 100%, 88%, 88%, and 54% of the samples, respectively. OPLs with high-risk LOH profiles had increased epithelial PD-L1 expression (P = 0.007), intraepithelial CD68+/PD-L1+ cells (P = 0.002), and a trend towards more CD3+/CD8+ cells in the stroma (P = 0.06) but not in the epithelium (P = 0.97), compared with low-risk LOH OPLs. Increased epithelial PD-L1 expression was associated with inferior OCFS on univariate (P = 0.023), and multivariate analysis including LOH status and EGFR CNG as co-variates (P = 0.018). Conclusions: High-risk OPLs defined by LOH profiles had increased PD-L1 expression in epithelial cells and intraepithelial macrophages, as well as stromal CD3+/CD8+ immune infiltration. Higher PD-L1 expression was associated with increased oral cancer risk. The findings may support evaluation of (PD-1-targeted) immunoprevention strategies in high-risk OPLs.
Ten year experience of an integrated cancer prevention center screening for multiple cancer types.
Authors: Wolf Ido , Leshno Ari , Liberman Eliezer , Gur Eyal , Elran Hanoch , Sror Miri , Harlap-Gat Amira , Jean Maayan , Steiner Moran , Galazan Lior , Av Galit , Blachar Arye , Kessler Ada , Golan Orit , Shapira Shiran , Geva Ravit , Arber Nadir 
Published: September 2018

1549 Background: Cancer is the leading cause of mortality worldwide. Prevention and early detection are pivotal tools for reducing cancer burden. Methods: We describe the 10 year experience (2006-2016) of an integrated cancer prevention center that provides screening for prevention and early detection of 11 most common cancer types. Healthy individuals (20-80 yr) were included. Extensive clinical and epidemiological data was obtained. DNA was extracted from all participants and genotyped for APC I1307K and E1317Q. Patients were examined by specialists in internal medicine, surgery, plastic surgery, OBGYN, urology, oncology, oral surgery, gastroenterology, and others. Women underwent vaginal US and pap smear and (40yr) mammography and US/MRI with a clinical indication. PSA and free PSA for Men ( > 40yr). LDCT for heavy smokers. Colonoscopy was recommended to all subjects ( > 40yr). Results: A total of 6258 (49%) men and 6461 (51%) women mean age 47.0±11.5 year were screened. New malignant lesions were detected in 389 (1.75%) of screeners. The most common cancers were of skin (74, 0.6%), prostate (62, 0.5%), thyroid (51, 0.4%), breast (36, 0.3%), colorectal (22, 0.2%), ovarian (19, 0.1%), uterus (14, 0.1%), testis (12, 0.09%) urinary (9, 0.07%) and lung (10, 0.08%). In 28 patients (0.22%) more than one cancer was detected. Twenty eight of the cancer patients (7.2%) died after 32.4±28.1 months at a mean age of 69.4±14.2 years. Significantly, better than the expected cancer mortality. The APC I1307K and E1317Q variants were detected in 572 (4.8%) and 182 (1.5%) subjects respectively. First degree family member with cancer (OR = 2.02), I1307K carrier ship (OR = 1.53), female gender (OR = 1.23) and advanced age (OR = 1.06) were all associated with statistically significant (P < 0.05) increased cancer risk. Advanced age and first degree family history were also associated with detection of more than one cancer types. Conclusions: One stop shop screening, in the setting of a multidisciplinary outpatient clinic, is feasible and can prevent and detect cancer at an early stage. It significantly improve morbidity and mortality. Impressively the APC I1307K carries an overall increase cancer risk.
Risk of breast or ovarian cancer in family members who do not carry the BRCA1 or BRCA2 family mutation: Findings from the EMBRACE study.
Authors: Girardi Fabio , Barnes Daniel R. , Barrowdale Daniel , Frost Debra , Easton Douglas F. , Antoniou Antonis C. ,   EMBRACE Collaborators
Published: September 2018

1558 Background: BRCA1/BRCA2 true-negatives are proven non-carriers of the BRCA mutation segregating within their family. Currently, there is no conclusive evidence on the risk of developing breast or ovarian cancer in these individuals, potentially leading to non-uniform clinical practices. The purpose of this study was to estimate breast and ovarian cancer risks for true-negatives from the EMBRACE prospective cohort study. Methods: Risks were calculated separately for incident invasive breast cancer and epithelial ovarian cancer (EOC). We used cohort analysis to estimate incidences, cumulative risks and standardised incidence ratios (SIRs). Results: A total of 1895 unaffected women were eligible for inclusion in the breast cancer analysis and 1736 for the ovarian cancer analysis. There were 23 incident invasive breast cancers and 2 EOCs diagnosed during follow-up. The cumulative risk of invasive breast cancer was 9.4% (95% CI 5.9%-15%) by the age of 85-years, whilst the corresponding risk of EOC was 0.6% (95% CI 0.2%-2.6%). The SIR for breast cancer was 0.93 (95% CI 0.62-1.40) in the overall cohort, 0.85 (95% CI 0.48-1.50) in non-carriers from BRCA1 families and 1.03 (95% CI 0.57-1.87) in non-carriers from BRCA2 families. The SIR for EOC was 0.79 (95% CI 0.20-3.17) in the overall cohort and 1.74 (95% CI 0.44-6.98) in non-carriers from BRCA2 families. Conclusions: This is the largest cohort to date of prospectively ascertained true-negatives from BRCA1/ BRCA2 families. Our results did not provide evidence for elevated risks of invasive breast cancer or EOC in proven non-carriers. Risk-reducing bilateral mastectomy and risk-reducing salpingo-oophorectomy may not be appropriate for these individuals. Female relatives of a known BRCA1/BRCA2 mutation carrier should be advised towards genetic testing to avoid unnecessary surgical procedures. However, we were not able to investigate variation in risks by cancer family history. Therefore, we cannot rule out that risks may be slightly higher for close relatives of affected mutation carriers. In such cases, model-based estimates incorporating family history, such as those given by BOADICEA, can be used in the counselling process.
Hormone replacement therapy (HRT) among BRCA mutation carriers.
Authors: Centers Nicole , Ivanov Olga , Buffington Cynthia , Caceres Aileen 
Published: September 2018

1561 Background: BRCA mutation carriers are often offered risk-reducing surgery (oophorectomy, hysterectomy) and medication regimens (hormone modulators, chemotherapy) in a preventative format. These therapies cause premature menopause and associated symptoms including reduced libido and sexuality. Hormone replacement therapy (HRT) is beneficial in alleviating climacteric symptoms of menopause. However, due to high risk for breast cancer in BRCA mutation carriers, many within the healthcare community oppose the use of HRT, despite recent studies that fail to demonstrate an adverse effect on oncologic outcomes. The purpose of this study was to identify current HRT practices among BRCA1,2 mutation carriers. Methods: The study population included 763 BRCA1,2 mutation carriers (52% previvors, 48% survivors) who are members of Facing Our Risk of Cancer Empowered, a support, education, and advocacy group for individuals with gene mutations. Data was collected via an online survey that included questions pertaining to patient characteristics, preventative procedures, menopausal status and symptoms, HRT use, and provider recommendations. Results: According to the survey findings, 73% of BRCA mutation carriers were postmenopausal (59% previvors, 88% survivors) and, among these, 81% had become menopausal prematurely due to risk-reducing surgery or medications. Major postmenopausal concerns of BRCA mutation carriers involved low libido/sexuality (78%) and an increased risk for weight gain (83%), cardiovascular disease (77%), and osteoporosis (65%). Despite the high incidence of premature menopause and associated symptomatology of the population, HRT usage was low (13% previvors, 28% survivors). According to the survey respondents, only 26% of healthcare providers for the previvors and 8% for the survivors favored HRT use. Conclusions: High rates of premature menopause with related symptoms occur among BRCA1,2 mutation carriers in association with cancer preventative therapies. Despite the young age of this postmenopausal population, only a small percentage are on HRT. These findings suggest the need for improved education to patients and providers regarding HRT and cancer risk, as well as the exploration of HRT options.
BROCA gene panel testing in African descendants from northeastern Brazil: Genetic susceptibility profile of an admixed population.
Authors: Felix Gabriela Espirito Santo , Zheng Yonglan , Guindalini Rodrigo Santa Cruz , Machado-Lopes Taisa Manuela Bonfim , Zhang Jing , Côrtes Juliana , Oliveira Pollyanna Carozo , Santos Irlânia S , Bomfim Thais , Garicochea Bernardo , Toralles Maria Betania , Abe-Sandes Kiyoko , Nascimento Ivana Lucia Oliveira , King Mary-Claire , Walsh Tom , Olopade Olufunmilayo I. 
Published: September 2018

1572 Background: The rising global burden of breast cancer (BC) in developing countries demands innovative interventions to accelerate progress in cancer control and prevention. Given the high rates of aggressive young onset breast cancer in Brazil, we sought to examine genetic susceptibility to the disease in the State of Bahia in the Northeast of Brazil, which has the largest population of African descendants. Methods: We screened cases, high-risk breast cancer patients with and without family history of breast cancer, and controls (cancer-free women) for twenty-eight breast cancer susceptibility genes using a validated targeted capture and multiplex sequencing approach – the BROCA panel. Each participant gave informed consent under IRB approved protocols and provided clinical-pathological and epidemiological data. Results: A total of 292 consecutive and unrelated individuals (173 cases and 119 controls) were included. Nearly 2/3rds of the cases (116/173) and about 90% of the controls (108/119) self-reported as African-descendant. Mutations considered pathogenic were identified in 37 (21.4%) cases and in one control (0.84%, RAD51C c.266insA), OR = 27.75 and p = 0.008. The mutated genes in cases were BRCA1 (in 12 patients), BRCA2 (10), ATM (3), PALB2 (3), BRIP1 (3), BRCA2/ BARD1 (1), FAM175A (1), FANCM (1), NBN (1), SLX4 (1) and TP53 (1). Three recurrent mutations accounted for 12.4% (9/37) of the total: 3 BRCA1 c.3331_3334delCAAG (known European mutation), 3 BRCA1 c.211A > G (known Galician mutation), and 3 PALB2c.1671_1674delTATT (novel mutation). Conclusions: Mutations in BRCA1 and BRCA2 (64.85%) or another breast cancer gene (35.15%) occur in one in five high-risk breast cancer patients in the largest study of Northeastern Brazil to date, and a significant proportion were recurrent mutations of European origin, which can be explained by the admixture pattern of the Brazilian population. This result underscores the importance of using multigene panel in cancer genetic epidemiologic research of understudied populations where unexpected findings, such as the recurrent and novel variant in PALB2 c.1671_1674delTATT, can be detected.
Smoldering Waldenström’s macroglobulinemia (SWM): Analysis from the National Cancer Database (NCDB).
Authors: Pophali Priyanka Avinash , Bartley Adam C. , Kapoor Prashant , Gonsalves Wilson I. , Ashrani Aneel A. , Marshall Ariela L. , Siddiqui Mustaqeem Ahmad , Go Ronald S. 
Published: September 2018

1573 Background: There are no epidemiologic studies of SWM due to lack ofICD codes specific for smoldering status. Methods: The NCDB represents ~70% of cancer cases in the US. It records the time to initial treatment or reasons for not receiving treatment. Using the 2004-2012 database, we estimated the overall proportion of new adult WM cases that are smoldering and analyzed outcomes according to socio-geo-demographic subgroups. Patients who were recommended treatment (irrespective of administration status) or died within 120 days of diagnosis were considered to have active WM while those who did not require treatment and had follow-up ≥120 days after diagnosis were considered to have SWM. Results: 2322 (28%) of 8302 patients diagnosed with WM were SWM. Median age at diagnosis was 71 (range 28-90) years. Median age did not change significantly during 2004-2012 (P = 0.83) but the proportion of smoldering disease decreased with time (P = 0.02). The proportions of SWM according to socio-geo-demographic subgroups are shown in the Table. Conditional survival (given survival to 4 months) at 5-years was 66% vs. 70% and at 10-years was 38% vs. 46% for active WM vs. SWM, respectively. The OS for SWM was significantly better among females and those who were younger, privately insured, with less co-morbidities and residing closer to a health facility. However, the OS did not differ by racial groups or era of diagnosis 2004-2008 vs 2009-2012. On multivariate analysis, sex, age group and co-morbidity index were significant factors affecting OS while race, insurance, distance from health facility and era of diagnosis were not. Conclusions: Approximately 28% of WM cases in the US are smoldering at diagnosis. The prevalence of SWM varied among socio-geo-demographic subgroups. Sex, age and co-morbidities significantly affect survival of SWM. [Table: see text]
Melanoma genetic testing to promote reductions in tanning: Results from the Utah BRIGHT project.
Authors: Aspinwall Lisa , Stump Tammy K. , Taber Jennifer M. , Kohlmann Wendy , Champine Marjan , Drummond Danielle , Cassidy Pamela , Leachman Sancy Ann 
Published: September 2018

1582 Background: Predictive genetic testing for familial cancer may alert people to highly elevated risk prior to disease onset. Genetic test reporting has been shown to improve uptake of prophylactic screening and procedures, but whether test reporting also promotes increased performance of primary preventive behavior is unknown. Methods: Unaffected adult participants ( N= 124) from high-risk melanoma families, ages 16-69 (mean = 35.24, 52% men) were enrolled. Participants from families that carried a CDKN2A/p16 mutation received a personal genetic test result and counseling about management recommendations whereas control participants from families without a CDKN2A/16 mutation received equivalent counseling and management recommendations based on family history alone. Photoprotection outcomes were compared between CDKN2A/p16 participants (31 carriers, 44 noncarriers) and the no-test control group ( n= 49), allowing the effects of receiving a genetic test result to be distinguished from the effects of counseling alone. Assessments were seasonally timed to capture tanning during the summer months. Melanin Index (MI) scores, measures of skin tanning obtained through reflectance spectroscopy, were assessed at the dorsal wrist and face. Tanning of the dorsal wrist and face were calculated by subtracting baseline MI scores at an unexposed site on the same individual. Results: Multilevel model analyses examined changes in tanning over time while controlling for clinician-rated skin type, age, gender, date of assessment, and group differences in phenotypic factors and family medical history. Participants who received positive test results were significantly less tan at the wrist one year after their previous summer baseline ( b= -.11, p< .001). No-test controls and noncarriers had no change in tanning. The magnitude of decrease in tanning measurements observed among CDKN2A/ p16 carriers approximated one skin type. Facial tanning did not differ from baseline for any group. Conclusions: A positive melanoma genetic test result promotes reduced UVR exposure. Future research should examine why positive genetic test reports were more motivating to patients than equivalent counseling based on family history.