bluuebunny/crossref_metadata_2025_split huggingface dataset:
Routine universal screening for Lynch syndrome in colorectal cancer patients in the community setting.
Authors: Goldberg Jeffrey M. , Lewis Andrea L. , Alabek Michelle , Dreher Cara , Brooks Sandra Elane 
Published: March 2020

1512 Background: Identification of colorectal cancer (CRC) cases that are due to Lynch Syndrome (LS) is important to prevent secondary malignancies or development of additional malignancies among relatives. Utilization of clinical criteria to select CRC patients for laboratory testing fails to identify a significant proportion of patients whose CRC is due to LS. Therefore, universal screening for LS among CRC patients has been advocated by the Evaluation of Genomic Applications in Practice and Prevention Working Group. However, the feasibility of routine universal screening has not been evaluated in a community-based, non-research setting. We implemented a universal screening protocol for LS as part of routine care of CRC at Norton Healthcare, a multi-institutional community-based healthcare organization. Methods: Beginning in October 2009, all resected CRC tumors automatically underwent immunohistochemistry analysis (IHC) for Lynch Syndrome-associated mismatch repair gene (MMR) expression. Selected patients who underexpressed MLH1 also underwent testing for the BRAF V600E mutation. Patients who had a BRAF V600E mutation were considered to have sporadic CRC. All other patients with abnormal IHC were automatically referred for genetic counseling. We retrospectively reviewed the outcomes of genetic counseling in all patients referred through this universal screening protocol. Results: Between October 2009 and December 2011, 388 patients underwent resection of CRC, all of whom had IHC for MMR expression. Seventy patients were identified as having abnormal IHC. Sixty-two had MLH1/PMS2 underexpression, of which 18 underwent BRAF testing and 13 had a BRAF V600E mutation. Eight had MSH2/MSH6 underexpression. Nine patients have been confirmed to have LS, 31 have been found not to have LS, and 19 are in the process of evaluation. Seven patients declined genetic counseling, and 4 died before they could be adequately evaluated. Conclusions: Universal screening for CRC due to LS, using IHC with select BRAF V600E mutation testing and automated referral for genetic counseling, is feasible in the community setting. Funded in part with federal funds: NCI, NIH, Contract No. HHSN261200800001.
Pathologic findings at risk-reducing salpingo-oophorectomy among women at increased ovarian cancer risk: Results from GOG-199.
Authors: Mai Phuong L. , Sherman Mark E , Piedmonte Marion , Ioffe Olga B. , Ronnett Brigitte M. , Van Le Linda , Mutch David Gardner , Cohn David E. , Thigpen J. Tate , Tewari Krishnansu Sujata , Disilvestro Paul , Kauff Noah D. , Lu Karen H. , Greene Mark H. 
Published: March 2020

1519 Background: Although risk-reducing salpingo-oophorectomy (RRSO) is a standard management option for women with BRCA1/2 mutations, the lack of large, prospective cohort studies makes estimating the prevalence of cancer at RRSO problematic. Methods: GOG-199 is a large, non-randomized multi-center trial which enrolled women at high-risk (due to BRCA mutations or strong family history) of ovarian cancer, comparing surgery at enrollment with serial transvaginal ultrasound and CA-125 screening. RRSO specimens were processed according to a standardized tissue processing protocol including 2-3mm sectioning of both ovaries and tubes. Results: 2,605 participants were accrued to GOG-199. Of the 1 030 enrolled in the baseline RRSO cohort, 28 were ineligible and 36 declined surgery after enrollment, resulting in 966 baseline RRSO. Pathology review demonstrated 4 tubal intraepithelial carcinoma and 20 serous pelvic cancers, of which 12 were identified only microscopically. Among the 20 serous cancers, the predominant or exclusive site of involvement was ovary in 10, fallopian tube in 5, and peritoneum in 5 cases. In addition, 6 endometrial cancers (among the 515 undergoing concomitant hysterectomy) and 3 adenocarcinomas suggestive of metastasis were identified. The serous pelvic cancer prevalence was: entire cohort=2.1% (20/966), all BRCA mutation carriers=3.2 (18/558), BRCA1 mutation carriers=3.7% (12/325), BRCA2 mutation carriers=2.6% (6/231), and mutation-negative=0.5% (2/402). Compared to those without cancer, women with serous pelvic cancer were older at surgery (p< .001), and more often menopausal (vs pre-menopausal, p= .002), nulliparous (vs parous, p=.04) and never users of tamoxifen (vs ever users, p= .04). Serous pelvic cancers were more frequent in BRCA mutation carriers (vs no mutation, p= .004), and among carriers, more common in those with BRCA1 mutations (vs BRCA2 mutation, p= .02). Conclusions: The prevalence of serous pelvic cancers in this cohort was 3.2% among carriers vs 0.5% among the mutation-negative but with a strong family history. Our data will be useful when counseling women at increased ovarian cancer risk who are contemplating risk-reducing surgery.
Contribution of TP53 p.R337H mutation to breast cancer prevalence in Brazil.
Authors: Ashton-Prolla Patricia , Osorio Cynthia ABT , Koehler-Santos Patricia , Graudenz Marcia S , Palmero Edenir Inez , Fernandes Gabriela , Micheli Rodrigo , Martel-Planche Ghyslaine , Achatz Maria Isabel , Soares Fernando Augusto , Goldim Jose Roberto , Caleffi Maira , Hainaut Pierre , Camey Suzi Alves , Giacomazzi Juliana 
Published: March 2020

1522 Background: The exact contribution of TP53 germline mutations, associated with Li Fraumeni Syndrome, to the overall burden of cancer is still only partially known. Studies in Southern and Southeastern Brazil have shown that a specific germline mutation at codon 337 (c.1010G>A; p.R337H), has incomplete penetrance and may be present in a significant number of subjects (estimated frequency at the populational level of 1:300 individuals). In an exploratory approach, the aim of the study is to assess the frequency of the p.R337H mutation in women from different Brazilian regions, diagnosed with breast cancer (BC) before 46 and after 55 years of age, and unselected for family history of cancer. Methods: Formalin-fixed paraffin-embedded (FFPE) non-tumoral tissue (lymph nodes or normal breast) of women diagnosed with BC between 2000 and 2010 in 3 pathology laboratories from the Brazilian cities of Porto Alegre, São Paulo and Barretos were obtained retrospectively and analyzed after anonimization. Genomic DNA was isolated with standard methods and genotyping performed in duplicates by qPCR (TaqMan assay). Confirmation of all mutation-positive and a sample of mutation-negative cases were done by TP53 exon 10 sequencing or by a second independent qPCR analysis. Results: Analysis of 515 BC-affected women identified the p.R337H mutation in the germline of 70 (8,6%) cases: 49/403 (12,1%) diagnosed before 46 years and 21/412 (5,1%) diagnosed after 55 years. BC occurred earlier in p.R337H mutation carriers than in non-carriers (p=0.001). Conclusions: Preliminary analysis in a sample of women with BC indicates that p.R337H founder mutation is present in a high proportion of cases, especially those diagnosed at a young age. Regional genetic background and recruitment strategies may account for the different mutation frequencies observed in the centers of study. The occurrence of this mutation at such a high frequency in a particular geographic region has important implications for disease management and cancer risk counseling for these patients and families. This mutation likely contributes to a significant proportion of the health burden associated with BC in Brazil. Financial support: FIPE-HCPA, CAPES, FAPERGS and Glaxo Smith Kline.
Racial disparities in treatment patterns and clinical outcomes in patients (pts) with HER2+ metastatic breast cancer (MBC).
Authors: Brufsky Adam , Yardley Denise Aysel , Ulcickas Yood Marianne , Tripathy Debu , Kaufman Peter Andrew , Mayer Musa , Feng Shibao , Abidoye Oyewale O. , Rugo Hope S. 
Published: March 2020

1526 Background: Data examining prognosis and treatment outcomes for black pts with HER2+ MBC are limited. Methods: registHER is a large, observational cohort of pts (N=1,001) with HER2+ MBC diagnosed w/in 6 mos of enrollment and followed until death, disenrollment, or 6/09 (median follow-up 27 mos). Demographics, treatment patterns, and clinical outcomes were described for black (n=126) and white pts (n=793). Progression Free Survival (PFS) and Overall Survival (OS) were examined. Multivariate analyses adjusted for baseline and treatment factors. Results: Black pts were more likely to be obese (BMI ≥ 30), have diabetes, and a history of cardiovascular disease (CVD) than white pts (Table). Black pts were less likely to have estrogen receptor (ER)/progesterone receptor (PR)+ disease and more likely to present with stage IV MBC. In trastuzumab (T)-treated pts, incidence of cardiac safety events (grade ≥3) was higher in black (13/119 [10.9%]) than white pts (59/746 [7.9%]). Unadjusted median OS (mos) was significantly lower (blacks: 27.1, 95%CI 23.2-32.1; whites: 37.3, 95%CI 34.6-41.1) and median PFS (mos) was lower (blacks: 7.0, 95%CI 5.7-9.7; whites: 10.2, 95%CI 9.3-11.2) in black than white pts. The adjusted OS hazard ratio (HR) for black vs. white was 1.32 (95%CI 1.04, 1.69); the adjusted PFS HR was 1.31 (95% CI 1.07, 1.61). Conclusions: These population-based data show poorer prognostic factors and independently worse clinical outcomes in black vs. white pts, and represent the largest database to date with black pts with HER2+ MBC. Further research is needed to explore the basis for the differences noted in this hypothesis-generating analysis. [Table: see text]
Associations between allergies and risk of hematologic malignancies: Results from the Vitamins and Lifestyle (VITAL) cohort study.
Authors: Shadman Mazyar , Walter Roland B. , DeRoos Anneclaire , White Emily 
Published: March 2020

1527 Background: Several case-control studies have suggested a reduced risk of hematologic malignancies (HMs) for individuals with allergies, but results have been inconsistent, and prospective cohort studies have not confirmed this association. Herein, we used the large prospective VITAL study to examine this association. Methods: 64,847 men and women, aged 50-76, completed a baseline questionnaire in 2000-2002 and reported on their current allergies and history of physician-diagnosed asthma. Individuals with prior cancer other than non-melanoma skin cancer were excluded from this analysis. Incident HMs were identified through December 2009 by linkage to the SEER registry; those with a diagnosis of a non-HM during follow-up were censored at the time of that diagnosis. Multivariable Cox proportional hazards models were built with adjustment for sex, race/ethnicity, education, smoking, self-rated health, physical activity, history of anemia in the year before baseline, vegetable use and family history of leukemia or lymphoma. Results: Our analysis included 64,839 participants, among whom 681 (1.03%) incident HMs were found (MDS [69], AML (41], myeloproliferative disorders [60], mature B-cell neoplasms [262], chronic lymphocytic leukemia [107], plasma cell disorders [83], Hodgkin lymphoma [23], T-cell/NK-cell neoplasms [22], and others [14]). In multivariable analyses, a history of any allergy was associated with increased risk of HM (HR=1.21; 95% CI 1.02-1.43, p=0.02). This association was seen for current allergies to plants/grass/trees (HR 1.27 [1.06-1.52], p<0.001) but not for allergies to mold/dust, animals, insects, food, or medications. We did not find an association between a history of asthma and incident HMs (HR=0.95 [0.72-1.26]). Conclusions: Our study indicates a moderately increased risk of HMs inindividuals with a history of allergy, especially to plant, grass or trees. While no causality can be inferred, this may suggest a possible carcinogenic role for chronic stimulation of the immune system. However, further mechanistic investigations focusing on the biochemical markers of immune system as well as on possible gene effect modifiers are needed.
Potential risk of asbestos exposure among Japanese general population: Japanese general screening study for asbestos-related diseases (JGSARD).
Authors: Seki Nobuhiko , Yamaguchi Takuhiro , Eguchi Kenji , Kaneko Masahiro , Kusumoto Masahiko ,   JGSARD Study Group
Published: March 2020

1530 Background: The number of patients with pleural mesothelioma and lung cancer associated with asbestos exposure has recently been increasing in Japan. The aim of this study was to evaluate the results of screening for asbestos-related diseases in a group of Japanese general population. Methods: This prospective study was approved by the institutional review board. From 2006 to 2008, 9810 subjects (5283 men and 4527 women; mean age, 57 years) underwent chest radiography and low-dose CT examinations in 26 institutions in Japan. Among them, 6286 (64.1%) subjects underwent subsequent CT examinations after 2 years of interval. Clinical information such as histories of smoking and asbestos exposure was reviewed. Images were interpreted independently by 15 experienced pulmonologists or chest radiologists. Results: The history of asbestos exposure was definitely present in 1253 (12.8%) subjects, possibly present in 2058 (21.0%), and absent in 6499 (66.2%). On chest radiograph, pleural plaque and thickening were seen in 61 (0.6%) and 65 (0.6%) subjects, respectively. On low-dose CT, pleural plaque and thickening were identified in 264 (2.7%) and 245 (2.5%) subjects, respectively, and non-calcified pulmonary nodule/mass was seen in 1003 (10.2%). Furthermore, lung cancer was identified in 29 (0.3%) subjects. The history of asbestos exposure was not confirmed in 77 out of 264 subjects (29.2%) having pleural plaques on low-dose CT. Based on the logistic regression analysis, pleural plaque on low-dose CT was significantly correlated with male, age more than 60 years, smoking, and a history of asbestos exposure. Especially, total residential period in asbestos factory area as well as asbestos exposure work period showed significantly increased relative risk every 10 years. Similarly, lung cancer was significantly correlated with age more than 60 years, a history of asbestos exposure, and presence of pleural plaques. Conclusions: Our results indicate the presence of pleural plaques on low-dose CT among Japanese general population is closely associated with potential risk of asbestos exposure. However, about 30% of such subjects are not aware of a history of asbestos exposure.
Never-smoking women with lung cancer from the Spanish WORLD07 database.
Authors: Isla Dolores , Provencio Mariano , Majem Margarita , Felip Enriqueta , Vinolas Nuria , Campelo Rosario Garcia , de las Penas Ramon , Carcereny Enric , Alberola Vicente , Domine Manuel , Blanco Remei , Dorta Javier , Bernabé Reyes , Guillen Carmen , Vadell Catalina , Maestu Inmaculada , Rodriguez Delvys , Rubio-Viqueira Belen , Figueroa Salvador , Garrido López Pilar ,   ICAPEM Association
Published: March 2020

1531 Background: Gender differences in lung cancer (LC) have been reported, but with many unresolved issues yet. Tobacco causes the majority of women lung cancer (WLC), although the rate of never-smoking WLC is higher than in men. Several factors may play etiologic roles, and an in-depth understanding is needed. Methods: WORLD07 is a Spanish prospective, multicenter, epidemiologic female-specific LC database sponsored by ICAPEM, a professional association committed with WLC research. In order to improve the knowledge on never-smoking WLC, information has been extracted from WORLD07 database. Results: From October/2007 to October/2011, 1371 newly diagnosed WLC were included in an e-database from 32 centers, 539 (39.3%) never-smoking. Patient (p) characteristics: median age 71.1 years(y); median age of menarche 13y.; motherhood 91.2% (median 2.3 children, median age at first child 26.4y); oral contraceptive use 11.9%; postmenopausal 88.9% (median age of menopause 49y); HRT 5.2%; second-hand smokers 40% (work-exposure 17.1%, home-exposure 88.8%); obesity 16.3%; familiar history of cancer 39.9% (LC 29.8%); previous history of cancer 13% (breast/lung/cervix: 41.4/5.7/2.9%); current LC histology(%): adenocarcinoma/SqCC/LCC/SCLC: 83.4/6.2/5.5/3.9; EGFR mut+ (268 p analyzed): 55.5% (exon 19/20/21(%): 61.1/7.4/36.9); TNM NSCLC I/II/III/IV(%): 14/3.3/19.8/60.3. Treatment: EGFR-TKI in p EGFR mut+, stage IV(1st-/2nd-line)(%): 51.7/15.4; stage IV NSCLC (1st-line/2nd-line): platinum-based CT 42.5%, EGFR-TKI 33.5%, combinations with bevacizumab 2.9% / EGFR-TKI 15.8%. Overall survival: median 27 months(m), 1/2-y(%) 74.8/55.2; stage IV NSCLC: median 20.5m, 1/2-y(%) 67/46; EGFR-mut+ p: median 27.3m, 1/2-y(%) 75/54.3. Conclusions: According to our e-database, WLC showed high rates of never-smokers (39.3%), and of relatives diagnosed with malignant tumours (39.9%, ≅1/3 LC). Adenocarcinoma was the most frequent histology (76.1%), and more than half of the cases analyzed harboured EGFR mutations. Although 40% were second-hand smokers, further investigations are warranted. Survival outcomes remain satisfactory, as expected from this selected subgroup of p. Additional epidemiologic and treatment data will be presented.
Clinical characteristics of patients with malignant pleural mesothelioma (MPM) harboring somatic BAP1 mutations.
Authors: Zauderer Marjorie Glass , Bott Matthew Joseph , McMillan Robert , Sima Camelia S. , Rusch Valerie W. , Krug Lee M. , Ladanyi Marc 
Published: March 2020

1541 Background: Efforts to elucidate tumorigenic mutations in MPM are essential to advance therapy. We reported a 23% incidence of somatic mutations in BRCA1-associated protein-1 (BAP1) in 53 patients with MPM (Bott et al. Nat Genet 2011). Germline BAP1 mutations were also reported in two families with a predisposition to mesothelioma and uveal melanoma (Testa et al. Nat Genet 2011). While BAP1 somatic mutations are more common in poor prognosis uveal melanoma (84% class 2, 4% class 1; Harbour et al. Science 2010), the significance of these mutations in MPM is unknown. Therefore, we analyzed the clinical characteristics of patients with somatic BAP1 mutations in order to describe this newly identified subpopulation. Methods: We reviewed the charts of 121 patients with tumors tested for somatic BAP1 mutations. Results: Patient characteristics are in the Table. Twenty percent harbored somatic BAP1 mutations. Other than the percent of current or former smokers (75% BAP1 mutations, 42% BAP1 wild-type, p=0.006), no other clinical feature was significantly different among those with and without BAP1 mutations. Among 53 samples analyzed for NF2 mutation and p16 deletion, no correlation was seen with BAP1 mutation. Conclusions: Somatic BAP1 mutations occur in about 20% of MPM tumors. Aside from smoking history, no other differences in clinical characteristics or outcomes were noted in the BAP1 mutated cases. Similar efforts are needed to describe the features of germline mutations in order to define this new cancer predisposition syndrome. We are planning a prospective trial to further evaluate the prevalence of germline BAP1 mutations, and we are also exploring the therapeutic implications. [Table: see text]
Why do breast cancer programs fail to refer patients to genetic counseling upon obtaining family history?
Authors: Trosman Julia R. , Weldon Christine B. , Dupuy Danielle , Roggenkamp Betty , Ganschow Pamela , Schink Julian C. , Murphy Anne Marie 
Published: March 2020

1553 Background: Women with personal or family history suggestive of susceptibility to hereditary breast or ovarian cancer should be referred to genetic counseling (US Preventive Services Task Force, Ann Intern Med. 2005). Our goal is to examine whether this guideline is followed by breast cancer programs providing screening and treatment in a large urban area; and if not followed, why. Funded by Susan G. Komen for the Cure. Methods: Using the framework approach of qualitative research, we conducted interviews with 130 providers of breast cancer screening and treatment at 26 institutions in Chicago (18 community, 4 academic and 4 public hospitals). We interviewed radiologists, mammography technologists, nurses, surgeons, oncologists, internists, and patient navigators. Interviews were transcribed and coded; theme analysis was conducted; simple frequencies and Fisher's exact test were calculated. Results: While all 26 programs collect patient personal and family history, only one program has both a protocol for referral to genetic counseling and a genetic counseling service. All six interviewees from that program (6/130, 5%) report referring appropriate patients to genetic counseling, compared to none from other programs (p<0.0001). 90% of interviewees (118/130) did not perceive any role in raising patient awareness or referring them to genetic counseling. Among the 124 interviewees not referring to genetic counseling, 51 (41%) have genetic counseling available, but only 12% (6/51) of them view referring or making patients aware of genetic services as their responsibility; while none of the interviewees without genetic counseling services view this their responsibility (p<0.0001). None of the interviewees noted reimbursement of genetic counseling as a barrier to referral. Conclusions: The lack of accountability by care providers is a barrier to referring patients with personal or family history of breast or ovarian cancer to genetic counseling, even when the service is available. A comprehensive approach addressing access to genetic counseling, adoption of referral protocols and clear assignment of referral responsibilities is needed to ensure that women appropriately receive genetic assessment.
Cancer screening: Source of information and level of trust.
Authors: Morere Jean F. , Viguier Jérôme , Coscas Yvan , Pivot Xavier B. , Blay Jean-Yves , Eisinger Francois , Lhomel Christine 
Published: March 2020

1567 Background: Providing public information is critical for cancer control. EDIFICE surveys were conducted to provide a better understanding of the participation of the French population in cancer screening programs (colorectal, breast) or individual cancer screening (prostate). To evaluate sources of information in the general population and their level of trust, specific questions were addressed in the EDIFICE 3 survey. Methods: This third nationwide observational study, EDIFICE 3, was conducted by phone interviews among a representative sample of 1603 subjects aged between 40 and 75 years old, using the quota method. Questions on the source of information were: Concerning cancer screening, what are all your means of information? What level of trust (quoted from 1 to 10) do you have on the following media of information; your own general practitioner, physicians in general, patient associations, national health insurance system, health authorities, your close circle, radio and television, lay press, internet. Results: In the overall population, the most frequently quoted means of information for cancer screening were: radio and television (61%), general practitioners (52%), lay press (33%), institutional letters (19%) and internet (18%). People under 50 years old named significantly more often radio and television (66% vs 58%) and internet (24% vs 15%), while older people above 50 years old (target population for screening programs) more frequently named institutional letters (26% vs 7%). In a trust scale from 0 to 10, the best level of trust was achieved by general practitioners (8.2), patient associations (6.8), national health insurance system (6.6) and health authorities (6.2). In contrast, radio and television (5.7), lay press (5.2) and internet (4.6) were mistrusted. Overall, women and younger subjects were more trustful. Conclusions: Radio and television are the most frequently quoted source of information but paradoxically they are not highly trusted. The general practitioner appears to be the best option (trusted and used) for providing cancer screening information. As institutional letters were frequently quoted and highly trusted, they might be useful for informing the population even before the age of recommended screening.