bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends in synchronous invasive ductal carcinomas of the breast: A SEER database analysis.
Authors: Mehta Rutika Jitesh , Groman Adrienne , Jain Rohit K. , Levine Ellis Glenn 
Published: September 2018

e13081 Background: Synchronous breast cancers are uncommon and account for around 2% of all breast cancer diagnosis. Lobular histology is considered a risk factor for synchronous breast cancers. We sought to study the trends in synchronous breast cancer of ductal histology and influence of age by interrogating the SEER database. Methods: The SEER Research data 1973-2013 was interrogated for synchronous infiltrating ductal carcinoma diagnosis (2 diagnosis within 6 months of each other). Overall survival (OS), the primary endpoint, was defined as the time (in months) from diagnosis to death from any cause. Univariate proportional hazards modeling results were used to assess the effect of age, race and stage on overall survival. All associations were considered statistically significant at an alpha error < 0.01. All analyses were performed using SAS version 9.4. Results: 1469 cases were identified. Data was categorized by age group: ≤ 65 years or > 65 years. 60% were 65 years or younger. 85% were Caucasians, 9.6% African Americans and 5.2% others. Younger women (≤ 65 years) had a statistically higher proportion of Stage III/IV breast cancer diagnosis as compared to older women (33.4% vs 25.2%; p = 0.002). The incidence rate of synchronous breast cancers has been rising since 1973, more pronounced in the older age group. Incidence rates overall have risen from 0.09/100,000 persons in 1973-1980 to 0.29/100,000 persons in 2001-2013 (p < 0.001). Incidence rates for synchronous breast cancer in women > 65 years has increased from 0.30/100,000 persons in 1973-1980 to 1.03/100,000 persons in 2001-2013. The adjusted OS among older women is significantly worse than that of younger women (HR 1.05; 95% CI 1.04-1.05; p < 0.001). Conclusions: Better imaging techniques and breast cancer screening guidelines have likely improved breast cancer detection rates thus leading to a rise in the incidence of synchronous breast cancers. It can be speculated that underlying medical problems and advanced age result in more morbidity and subsequent mortality in older women with standard treatment. The finding of more advanced disease among younger women deserves scrutiny as to cause.
BMI change and abdominal girth as risk factors of breast cancer.
Authors: Suzuki Yusuke , Tsunoda Hiroko , Kimura Takeshi , Yamauchi Hideko 
Published: September 2018

e13082 Background: While obesity is considered the risk factors of breast cancer, Asian women are tends to be lower BMI compared with Western populations and there are not much reports that studied association between obesity and risk of breast cancer in Asian women. In this study, we analyzed the associations of breast cancer incidence and body mass index at age 18-20 (BMI 18-20y), BMI at research entry (BMI at entry), change of the BMI from BMI 18-20y to BMI at entry (BMI change), abdominal girth at research entry (AG), HbA1c [N] at research entry (HbA1c). Methods: We used data of the women who had undergone medical check-ups and opportunistic breast cancer screening at least twice at the Center for Preventive Medicine of St. Luke’s International Hospital between April 1, 2005 and March 31, 2014. Statistical analysis was done by using multivariate Cox proportional hazards model to investigate the hazard ratio (HR) at 95% confidence intervals (95% CI). Results: In this 10 year period, 30,109 women (20,043 women were premenopausal and 10,066 women were postmenopausal women) received opportunistic breast cancer screening at least twice. After analysis of 131656.6 person-years follow up during 10 years, 325 initial breast cancer cases were identified 202 cases in premenopausal women, and 123 cases in postmenopausal women. Among postmenopausal women, BMI change and AG were positively associated with breast cancer incidence. Women whose BMI change were major gain group (> +5.0) were significantly likely to develop breast cancer compared with stable group (BMI change were between -2.5 to +2.5) [HR: 1.902 (95% CI = 1.202-3.009)]. Large AG ( > 90cm) was significant risk to develop breast cancer versus less than 70cm [HR: 2.500 (95% CI = 1.091-5.730)]. In the analysis classified BMI18-20y more and less than 20 kg/m2, large BMI18-20y ( > 20 kg/m2) postmenopausal women with high HbA1c ( > 6.5) was more likely to develop breast cancer compared with low HbA1c ( < 5.5) [HR: 3.325(95% CI = 1.307-8.460)]. Conclusions: Increase of BMI after age of 18-20 years and large AG in postmenopausal women have positive association with breast cancer development. High HbA1c women whose BMI18-20y was over 20 kg/m2 are significantly to develop breast cancer.
Study to determine whether SNPs in CYP17A1, ESR1, and TNRC9 loci correlate with increased breast cancer risk and serum 25-OH vitamin D levels.
Authors: Yoshimoto Nobuyasu , Dong Yu , Sugiura Hiroshi , Terada Mitsuo , Kondo Naoto , Endo Yumi , Yamashita Hiroko , Toyama Tatsuya 
Published: September 2018

e13086 Background: Low serum 25-OH vitamin D (25-OH Vit.D) level is associated with a higher risk of breast cancer. Many single nucleotide polymorphisms (SNP) are associated with breast cancer risk, although the mechanisms underlying this association in most cases remain unclear. We attempted to address this issue by determining whether specific SNPs were correlated with breast cancer-associated biomarkers (BM). Methods: We analyzed estrogen receptor (ER)-positive breast cancer patients treated between Jan 2011 and Dec 2014. We measured serum testosterone and 25-OH Vit.D in pre- and post-menopausal women, and also measured estradiol in the latter group. We genotyped 7 individual SNPs both in premenopausal and postmenopausal women. We then looked for correlations between BMs and SNPs in all three genotypes (homozygotes of major alleles, heterozygotes and homozygotes of minor alleles) using the Kruskal-Wallis test. For each SNP locus associated with a trend or significant effect with regard to BM levels, a t-test was then applied to determine which of the two genotypes was responsible for the effect. Results: Four hundred thirteen women were enrolled (163 premenopausal patients, and 250 postmenopausal patients). There was a trend difference between CYP17A1 rs743572 and 25-OH Vit.D (p = 0.0888), ESR1 rs204210 and 25-OH Vit.D (p = 0.0534) in premenopausal women, and a significant difference between TNRC9 rs3803662 and 25-OH Vit.D (p = 0.026) in postmenopausal women. Among premenopausal women, 25-OH Vit.D levels were significantly lower in those with the high-risk rs743572 genotype TC when compared with TT individuals (19.2 +/- 6.7 ng/ml vs 22.9 +/- 8.7 ng/ml; p = 0.0125). Similarly, 25-OH Vit.D was significantly lower in women with the high-risk rs204210 genotype AG when compared with GG individuals (19.1 +/- 6.9 ng/ml vs 21.7 +/- 6.4 ng/ml; p = 0.0219). In postmenopausal women, 25-OH Vit.D was significantly lower in women with the high-risk rs3803662 genotype GG than those with the AA genotype (20.5 +/- 9.2 ng/ml vs 24.4 +/- 8.0 ng/ml; p = 0.0104). Conclusions: Specific SNPs in CYP17A1, ESR1, and TNRC9 genes may modulate breast cancer risk due to their influence on serum 25-OH Vit.D levels.
Epidemiology of lung cancer: A joinpoint analysis of temporal incidence and mortality trends in 38 countries.
Authors: Wong Martin CS , Chan Stephen Lam , Lao Xiang Qian , Tse Lap Ah , Ho KF , Goggins William 
Published: September 2018

e13091 Background: Lung cancer is the leading cause of cancer death worldwide. We examined the correlation between lung cancer incidence/mortality and country-specific socioeconomic development, and evaluated the most recent global patterns and trends of this cancer in 38 countries. Methods: We retrieved age-standardized incidence rates of lung cancer in 2012 from the GLOBOCAN database. Temporal patterns were assessed for all countries obtained from the Cancer Incidence in Five Continents volumes I-X and the WHO mortality database. Simple linear regression analysis was used to evaluate their correlations with Human Development Index (HDI) and Gross Domestic Product (GDP) per capita. The average annual percent change (AAPC) of the incidence and mortality trends in the most recent 10 years were evaluated from join-point regression analysis according to country and gender. The statistical significance of AAPC was ascertained comparing with zero, and all insignificant AAPCs were regarded as having “stable trends”. Results: The global incidence and mortality of lung cancer varied by 31-fold. Country-specific HDI was strongly correlated with age-standardized incidence (r = 0.70) and mortality (r = 0.67), and so was GDP per capita to a lesser extent (r = 0.24 to 0.55) (all p < 0.001). Among men, 22 and 30 (out of 38 and 36) countries showed declining incidence and mortality trends, respectively; whilst among women, 19 and 16 countries showed increasing incidence and mortality trends, respectively. The AAPCs ranged from -2.8 to -0.6 (incidence) and -3.6 to -1.1 (mortality) among countries with declining trend in men, whereas the AAPC range was 0.4 to 8.9 (incidence) and 1 to 4.4 (mortality) among countries with increasing trends in women. Among women, Brazil, Spain and Cyprus had the greatest incidence increase, and all countries in Western, Southern and Eastern Europe had increasing mortality. Conclusions: Countries with higher socioeconomic development had higher lung cancer incidence and mortality. The incidence and mortality rates of lung cancer were increasing in many countries among women but declining in most countries among men, highlighting the need for regular surveillance and global preventive measures.
Somatic versus germline BRCA mutations screening in ovarian cancer.
Authors: Nunes Hugo SM , Machado Patricia , Fragoso Sofia , Santos Sidonia , Silva Fernanda , Felix Ana , Luís Ana , Opiniao Ana , Clara Ana , Bento Sandra , Miranda Ana , Francisca Ana , Vaz Fatima H. 
Published: September 2018

e13100 Background: ovarian cancer (OC) with germinal or somatic BRCA mutations responds better to platinum and to PARP-inhibitors. There is great enthusiasm about BRCA somatic screening. Our aim was to analyse the correlation between BRCA somatic and germline mutational profile. Methods: a cohort of 23 pts was obtained by cross-linking OC pts from the South Portuguese Cancer Registry, between 2009-2014 and BRCA mutation carriers identified in our Clinic. Medical records were reviewed: demographic and clinico-pathologic data obtained. Germinal screening: pts were pre-screened for the BRCA2 Portuguese founder mutation (PFM), analysed for BRCA point mutations (different screening methodologies were used in diagnostic timeline: initially CSGE, then CSCE and finally NGS) and for large rearrangements by MLPA. Somatic screening: DNA was extracted from 5 sections of 10µm of FFPE tissue and analysed for BRCA1/2 genes by NGS. Results: clinico-pathological features of the 23 pts revealed mainly high-grade serous histology (96%). Mean age at diagnosis was 54 years old (33-76); BRCA2 were older than BRCA1 carriers (62 vs 51). Most pts presented at advanced stage (70% stages III-IV; 30% stage I-II). Seventeen were BRCA1 carriers and 6 were BRCA2 (5 of those PFM, a large insertion of an Alu element). Somatic correlation: 8 pts (5 BRCA1, 3PFM) were already analysed and 100% correlation was observed for all point mutations. One additional BRCA2 somatic mutation was detected (with a variant allele frequency of 53% whereas 2 others were < 7%); interestingly exclusive somatic mutations were only observed in PFM carriers (known not to be NGS detectable). The remaining 15 pts are under analysis. Conclusions: it was expected that the PFM and other large rearrangements would not be detected with NGS. A specific somatic screening for the PFM may be possible but other rearrangements are found by MLPA in our population (10% of all BRCA mutations). Preliminary data adds to the evidence that NGS OC somatic screening will identify all germinal point mutations and an indeterminate number of additional pts with exclusive somatic mutations. An ideal correlation needs integration of differenttechniques that may increase complexity, time and cost.
Comprehensive next generation sequencing assay and bioinformatic pipeline for identifying pathogenic variants associated with hereditary cancers.
Authors: Puig Oscar , Joseph Eugene , Jaremko Malgorzata , Kellogg Gregory , Wisotzkey Robert , Shraga Roman , Patel Bonny , Pollock Andrew , Fox Rebecca , Niknazar Mohammad , Parets Sasha , Duverger Georges , Chang Chihyu , Bisignano Alexander 
Published: September 2018

e13105 Background: Diagnosis of hereditary cancer syndromes involves time-consuming comprehensive clinical and laboratory work-up, however, timely and accurate diagnosis is pivotal to the clinical management of cancer patients. Germline genetic testing has shown to facilitate the diagnostic process, allowing for identification and management of individuals at risk for inherited cancers. However, the laboratory diagnostics process requires not only development and validation of comprehensive gene panels to improve diagnostic yields, but a quality driven workflow including an end-to-end bioinformatics pipeline, and a robust process for variant classification. We will present a gene panel for the evaluation of hereditary cancer syndromes, conducted utilizing our novel end-to-end workflow, and validated in the CLIA-approved environment. Methods: A targeted Next-Generation Sequencing (NGS) panel consisting of 130 genes, including exons, promoters, 5’-UTRs, 3’-UTRs and selected introns, was designed to include genes associated with hereditary cancers. The assay was validated using samples from the 1000 genomes project and samples with known pathogenic variants. Elements software was utilized for end-to-end bioinformatic process ensuring adherence with the CLIA quality standards, and supporting manual curation of sequence variants. Results: Preliminary data from our current panel of genes associated with hereditary cancer syndromes revealed high sensitivity, specificity, and positive predictive value. Accuracy was confirmed by analysis of known SNVs, indels, and CNVs using 1000 Genomes and samples carrying pathogenic variants. The bioinformatics software allowed for an end-to-end quality controlled process of handling and analyzing of the NGS data, showing applicability for a clinical laboratory workflow. Conclusions: We have developed a comprehensive and accurate genetic testing process based on an automated and quality driven bioinformatics workflow that can be used to identify clinically important variants in genes associated with hereditary cancers. It's performance allows for implementation in the clinical laboratory setting.
Comparing actionable results for breast and colorectal cancer patients across multigene panels.
Authors: Fulk Kelly , Espenschied Carin , Profato Jessica , Reineke Patrick , LaDuca Holly , Smith Robina 
Published: September 2018

e13109 Background: Many multigene panel (MGP) options are available for hereditary cancer testing. Previously, management guidelines were only published for a few high-risk genes, but now such guidelines exist for most genes on MGPs. Many clinicians question which MGP(s) may be most appropriate for their patients. We examined the likelihood of a positive result for patients diagnosed with breast cancer (BC) or colorectal cancer (CRC) across several MGPs and assessed the potential impact of these results on patient care. Methods: Positive results, defined by the presence of at least one pathogenic or likely pathogenic variant, were assessed for patients with BC or CRC across various MGPs ordered 6/2012-6/2016 at one commercial laboratory. For BC, the MGPs used for comparison were a high-risk BC panel (up to 6 genes), a comprehensive BC panel (up to 17 genes), and a multi-cancer panel (up to 32 genes). For CRC, a comprehensive CRC panel (up to 17 genes) was compared to the 32 gene multi-cancer panel. Results: For both BC and CRC patients, the utilization of a MGP with more genes led to more positive results than a MGP with fewer genes, with the vast majority of additional findings occurring in genes with published management guidelines (Table). Conclusions: The majority of positive results occurring in genes on larger MGPs, but not smaller MGPs, are in genes with published management guidelines.These results can impact treatment decisions and cancer risk management, including earlier and/or more frequent screening, chemoprevention, and/or other measures. In some cases, positive results occurred in genes not associated with the patient’s cancer diagnosis, but may still impact risk management for other cancer(s). Further studies are needed to determine the impact of larger MGPs on clinical outcomes for patients and their families. [Table: see text]
Performance study of an amplification-based NGS test on clinical FFPE specimens in China’s first multi-center study.
Authors: Ye Feng , Zhou Xiaoyan , Shi Huaiyin , Liu Haijing , Liang Li , Teng Xiaodong , Wang Zhe , Xu Sanpeng , Wang Guoping , Chen Gang , Hou Yingyong , Wu Huanwen M. , Tang Tingdong , Liu Rui , Zhang Bo , Liang Zhiyong , Bu Hong 
Published: September 2018

e13112 Background: Next Generation Sequencing (NGS) assays provide a comprehensive view of clinically actionable variations in patients. The increasing application of NGS holds new promise towards accurate diagnosis, personalized treatment and precision medicine. Formalin-fixed Paraffin-embedded (FFPE) treatment remains to be the most popular format of tissue preservation. To further standardize the whole process of the application of NGS assays on FFPE tissues, the Chinese Medical Association Pathology Division organized a multi-center performance study of a NGS assay on more than 1,000 clinical FFPE specimens by inviting top pathology departments in the country. Methods: OncoAim Tumor Mutation and PharmGx Detection Kit (Singlera Genomics, Shanghai) was used for this study. Reference samples with known mutations and allele frequencies together with 1045 clinical FFPE specimens from 11 participating hospitals were tested. Among them, 615 Colorectal Cancer (CRC) and 430 Non-Small Cell Lung Cancer (NSCLC) FFPE samples were processed and sequenced on Illumina Miseq platform and Thermo ion torrent PGM platform, respectively. Results: The results on reference materials show 100% (Confidence interval = 100%) analytical sensitivity for mutations with MAF ≥ 10% when median coverage is ≥ 500X.Positive predictive value of > 99% was observed for mutations with MAF at 5% (data not shown). The median depth for CRC and NSCLC samples were 977Xand 828X, respectively. Among all CRC samples, 564 (91.7%) samples were found containing at least 1 clinical hotspot alteration. The top mutated genes were TP53, KRAS, APC, PIK3CA, SMAD4, BRAF, FBXW7, NRAS, PTEN, and ERBB2. For all the NSCLC samples, 304 (70.69%) were detected containing at least 1 clinical hotspot mutation. The top 10 mutated genes were EGFR, TP53, KRAS, PIK3CA PTEN, VHL, ERBB2, SMAD4, NFE2L2 and CTNNB1. Conclusions: In this study, we showed that the amplification-based NGS assay can achieve very high sensitivity and specificity for samples with median depth over 500X. The samples containing at least 1 clinical hotspot mutation were about 83% on average, suggesting NGS could be of great use for further characterization of the tissues.
Blood biomarker analysis to differentiate between pseudo-progression and true disease progression in post-treatment glioblastoma.
Authors: Hassan Bilal , Johnson Kimberly J. , Campian Jian Li 
Published: September 2018

e13501 Background: Current standard treatment for patients with glioblastoma (GBM) includes glucocorticoid therapy, temozolomide (TMZ), and radiation (RT) which may result in lymphotoxic and immunosuppressive effects. MRI use is currently unreliable in differentiating true from pseudo-progression pathology. Recent studies have suggested that total lymphocyte count (TLC) and CD4 cell count are associated with clinical outcomes. Our objective was to investigate whether TLC or CD4 may help to differentiate treatment effect (pesudoprogression) from tumor progression. Methods: Patients were eligible for this retrospective study if they had 1) GBM diagnosed between February 2010 and July 2015, 2) series of cell counts and clinical follow-ups monitored at Washington University, and 3) tumor progression documented by MRI and pathology. The data were analyzed using descriptive statistics, chi-square tests, Kaplan-Meier survival curves, and progression-free survival. Results: A total of 728 charts were reviewed, of which 45adults met eligibility criteria. The median age and KPS scores were 58 years and 80, respectively. MGMT was detected in 33% of patients and 69% of patients had undergone a gross total resection. Median TLC at baseline was 1700 cells/mm3 (range 400-3100). After the completion of RT/TMZ, TLC dropped 41% to a median of 1000 cells/mm3 (range 200-2900). Median TLC was 1000 cells/mm3 (range 300-2900) at the first MRI documented progression. Patients underwent surgery for this MRI documented progression. Pathology revealed that 62% of patients had true tumor progression, 33% had mixed treatment effect and residual tumor, and 4% had necrosis. The median time from diagnosis to progression was 15 months. There were no statistically significant differences in overall survival or progression free survival found in patients with higher vs lower TLC at baseline, completion of RT/TMZ, and time of progression. Conclusions: These preliminary results do not indicate that TLC level in GBM patients can differentiate between true disease progression and pseudo-progression. A larger sample size that includes patients with CD4 data is needed to confirm these results.