bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4217: Consumer credit, cancer treatment, and health among women with a history of breast cancer
Authors: Dean Lorraine T. , Schmitz Kathryn H. , Frick Kevin , Nicholas Lauren , Zhang Yuehan , Subramanian SV , Visvanathan Kala 
Published: July 2017

Abstract
Background: Breast cancer treatment may represent an economic shock that may be influenced by, or may influence a cancer survivor’s socio-economic position (SEP). Financial toxicity or economic burden due to cancer treatment and treatment’s adverse effects may be reflected in one’s consumer credit ratings; however, credit’s contribution to individual health for cancer survivors or those managing long-term adverse effects of cancer treatment has not been evaluated. This analysis examined associations between self-rated health outcomes of women with a history of breast cancer, type of cancer treatment, and presence of breast cancer-related lymphedema, a persistent adverse effect of treatment, and consumer credit rating.
Methods: From May to September 2015, 129 women from Pennsylvania and New Jersey were enrolled in the PAL Social and Economic Quality of Life cross-sectional study. All participants had a history of breast cancer, and completed a survey of: demographics, SEP, co-morbidities, SF-12 self-rated health, psychosocial stress, adjuvant cancer treatments (chemotherapy, hormone therapy, radiation), breast cancer-related lymphedema symptoms, and credit quality (5-point scale self-reported as poor to excellent). Multivariable linear regression measured the association between credit and health.
Results: Mean respondent age was 64, with 38.2% reporting excellent and 37.4% reporting very good/good credit. Participants completed cancer treatment on average 11.5 years ago. After adjusting for demographics and SEP, good credit was associated with a 4.5 (p=0.009) point increase in composite physical health t-score and -1.13 (p=0.02) decrease in psychosocial stress compared to women with poor credit, but was not associated with type of cancer treatment or lymphedema.
Conclusion: While credit was associated with self-rated health for women with an average 11.5 year history of breast cancer, current credit quality did not appear to be associated with type of cancer treatment previously received or with the presence of lymphedema, a persistent adverse effect of cancer treatment. It is still possible that cancer treatment may have influenced credit close to time of treatment, and credit was able to rebound since that time. Future work should test causal pathways between credit and health outcomes after cancer diagnosis.
Citation Format: Lorraine T. Dean, Kathryn H. Schmitz, Kevin Frick, Lauren Nicholas, Yuehan Zhang, SV Subramanian, Kala Visvanathan. Consumer credit, cancer treatment, and health among women with a history of breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4217. doi:10.1158/1538-7445.AM2017-4217
Abstract 4240: Determination of normative patterns of gene expression levels and breast cancer risk biomarkers in human breast milk
Authors: Ouzounova Maria , Lewis Georgina , Piranlioglu Raziye , Curry-McCoy Tiana , Yoo Wonsuk , Maihle Nita , Kim Sangmi , Korkaya Hasan 
Published: July 2017

Abstract
Parity and breastfeeding influence a woman’s risk of developing breast cancer. Understanding the underlying molecular changes in the breast will facilitate identification of additional factors during pregnancy and postpartum that modify breast cancer risk. Most prior studies in humans on this topic, however, have been cross-sectional studies comparing breast tissue samples from nulliparous versus post-pregnant women, and are limited in their ability to characterize longitudinal changes and within-person variations. Breast milk contains cells of the mature gland, and may have a potential as a noninvasive source for studying molecular characteristics of the pregnancy-associated changes in the breast and their impact on breast cancer risk. The objectives of this study were to (1) determine normative patterns of gene expression levels in longitudinally collected breast milk samples and (2) correlate gene expression data in relation to self-reported measures of psychosocial stress during pregnancy and postpartum period. Our preliminary results showed that the post-pregnancy gene expression levels in breast milk samples can be measured reproducibly over a short period of time. Whole-genome transcriptome analysis revealed that expression levels of the post-pregnancy genes are different in early (less than 3 month postpartum) and late lactation period (more than 6 month postpartum). Moreover cytokine expression profiling correlated expression of inflammatory cytokines with early versus late postpartum period. The unique contribution of this study is to capture longitudinal gene expression data from breast milk samples collected over the course of lactation, hence providing a valuable basis for future studies to identify differential dynamics associated with breast cancer susceptibility.
Note: This abstract was not presented at the meeting.
Citation Format: Maria Ouzounova, Georgina Lewis, Raziye Piranlioglu, Tiana Curry-McCoy, Wonsuk Yoo, Nita Maihle, Sangmi Kim, Hasan Korkaya. Determination of normative patterns of gene expression levels and breast cancer risk biomarkers in human breast milk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4240. doi:10.1158/1538-7445.AM2017-4240
Abstract 4254: Improved understanding of the etiology of breast cancer in young women through evaluation of the genomic landscape
Authors: Wilkerson Matthew D. , Dalgard Clifton L. , Shriver Craig D. , Ellsworth Rachel E. 
Published: July 2017

Abstract
Background Breast cancer is a disease where biological age and age at menopause are established risk factors, thus diagnosis of breast cancer in young women (&lt;40 years, YW) is not common, representing ~6% of breast cancer diagnoses annually. Germline mutations in cancer predisposition genes accounts for ~20% of breast cancer diagnoses in YW, thus the etiology of breast tumors for the majority of YW is unknown.
Methods Frozen tumor specimens and matched genomic DNA samples from 31 women diagnosed &lt;40 years were available. Whole genome sequencing (WGS) was performed by generating sequencing libraries from 1 mg input using the TruSeq PCR-free library preparation workflow and sequencing on the HiSeq X Ten at triple lane depth with 150bp paired-end reads. WGS was analyzed using the Hiseq Analysis Software Tumor Normal Workflow, Bioconductor: deconstructSigs and ad hoc integrated analysis and hypothesis testing.
Results Luminal A tumors from YW had significantly lower somatic mutational loads, copy number alterations and structural variants than other subtypes and structural variants on chromosome 17 were enriched in patients with the HER2-enriched subtype and HER2 status = 3+. Aging was the most common signature (28/31) followed by APOBEC activation (14/31). Signatures associated with defects in mismatch repair (9/31) and polymerase ϵ (10/31) were also detected in &gt;25% of patient tumors. Of the six patients with BRCA defect signatures, three had germline mutations in BRCA2 and one had a CHEK2 mutation. Mutational signatures could cluster patients into two groups, with the youngest patients (&lt;35 years) less likely to have signatures associated with aging but an enrichment in signatures of APOBEC, BRCA mutations and smoking; tumors within this group were more likely to be non-luminal A.
Conclusions Profiling the genome of tumors from YW supports the idea that most tumors are not characterized by profiles associated with genetic predisposition but rather processes such aging, APOBEC activation, mismatch repair, and defects in DNA replication. Of note, breast tumors in the youngest patients (&lt;35) have a different pattern of mutational signatures suggesting that even within YW, etiology differs by age.
Citation Format: Matthew D. Wilkerson, Clifton L. Dalgard, Craig D. Shriver, Rachel E. Ellsworth. Improved understanding of the etiology of breast cancer in young women through evaluation of the genomic landscape [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4254. doi:10.1158/1538-7445.AM2017-4254
Abstract 426: Targeted genome profiling in patients with advanced hepatocellular carcinoma treated with sorafenib
Authors: Kang Wonseok , Kim Kyung , Lee Joon Hyeok , Lim Ho Yeong , Park Woong-Yang , Lee Jeeyun , Paik Yong Han 
Published: July 2017

Abstract
Background/Objectives: Sorafenib is the only approved targeted agent as first-line treatment for advanced hepatocellular carcinoma (HCC). Unfortunately, many HCC patients are initially not responsive to sorafenib. Due to anatomic limitations and underlying liver dysfunction, genomic studies of HCC patients have not been actively pursued yet compared to other solid tumors; especially, in sorafenib-treated subset. In this study, we have retrospectively identified advanced HCC patients who had archival tumor tissues available for targeted genomic sequencing and who had been treated with sorafenib.
Methods: We performed targeted genomic profiling for 381 cancer-related genes from 42 HCC (32 hepatitis B virus-related, 1 alcohol-related, 7 unknown) patients treated with sorafenib at Samsung Medical Center, Seoul, Korea from July 2008 to October 2013. We excluded 2 patients who were lost to follow up for evaluation of treatment response to sorafenib.
Results: Of the 40 patients, there were 5 confirmed PRs, 7 SDs, and 28 PDs. In 40 patients, there were 6 CDKN2B amplifications, 4 NTRK1 amplifications, 2 MET amplifications, 2 FGF19 amplifications, 2 CCND1 amplifications, 1 EGFR amplification, 1 FGF23 amplification and 1 CCNE1 amplification. In cell cycle-related genes, those patients with aberrations were less likely to respond to sorafenib. Of note, two patients whose tumor had CCND1 amplifications had de novo resistance to sorafenib.
Conclusions: Our study demonstrates inter-patient heterogeneity in advanced HCC patients and the role of cell cycle-associated genes in resistance mechanism to sorafenib is being investigated.
Citation Format: Wonseok Kang, Kyung Kim, Joon Hyeok Lee, Ho Yeong Lim, Woong-Yang Park, Jeeyun Lee, Yong Han Paik. Targeted genome profiling in patients with advanced hepatocellular carcinoma treated with sorafenib [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 426. doi:10.1158/1538-7445.AM2017-426
Abstract 4264: Smoking exposure and quantitative levels of estrogen-receptor expression in ER+ breast tumors
Authors: Butler Eboneé N. , Baron John A. , Bensen Jeannette T. , Chen Mengjie , Conway Kathleen , Olshan Andrew F. , Troester Melissa 
Published: July 2017

Abstract
Introduction: Smoking is a suspected risk factor for breast cancer and has been linked to increased risk of estrogen-receptor positive (ER+) disease in some epidemiologic studies. Cigarette smoke has also been shown to have antiestrogenic effects, leading to a potentially contradictory hypothesis that smoking would lead to decreased risk of breast tumors driven by estrogen-signaling. Binary classification of breast tumors with respect to ER may mask quantitative associations between smoking and ER expression. Methods: Using data from the Carolina Breast Cancer Study (CBCS), we examined relationships between smoking and quantitative levels of ER expression from tumors of 1,297 women with ER+ disease (i.e., ≥ 10% of tumor cells ER+ by immunohistochemical analysis). We used multinomial logistic regression to estimate associations between categorical measures of smoking and quartiles of ER protein or ESR1 mRNA expression, represented by odds ratios (OR) and 95% confidence intervals (95% CI). We also examined associations between smoking and quantitative ER levels among women with ER+ breast tumors, stratified by menopausal status. Multivariate regression models include adjustment for age, race, stage, grade, and tumor size. Results: Quantitative ESR1 was positively associated with any history of smoking (i.e., current at time of diagnosis or former smoking) (OR: 1.96 and 95% CI: 1.24 to 3.10). In addition, smoking more than 1 pack of cigarettes per day was associated with high ESR1 expression (OR: 3.19 and 95% CI: 1.29 to 7.91) as was smoking duration of &gt; 20 years (OR: 2.08 and 95% CI: 1.16 to 3.74). Among former smokers, we observed higher ESR1 expression among those who quit 5-10 years prior to diagnosis. The magnitudes of association between smoking and quantitative levels of ESR1 expression were similar for both pre- and post-menopausal women, but were not reflected in similar association on the protein level. Conclusions: Among women with ER+ breast cancer, smoking dose and duration was positively associated with elevated ESR1 mRNA levels, regardless of menopausal status. Absence of this association for protein suggests that ESR1 RNA merits further consideration, but may suggest that ESR1 RNA more sensitively captures biological differences than ER protein expression.
Citation Format: Eboneé N. Butler, John A. Baron, Jeannette T. Bensen, Mengjie Chen, Kathleen Conway, Andrew F. Olshan, Melissa Troester. Smoking exposure and quantitative levels of estrogen-receptor expression in ER+ breast tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4264. doi:10.1158/1538-7445.AM2017-4264
Abstract 4265: Risks of familial breast cancer associated with known and proposed breast cancer susceptibility genes
Authors: Maxwell Kara N. , Slavin Thomas Paul , Lilyquist Jenna M. , Vijai Joseph , Neuhausen Susan L. , Hart Steven N. , Ravichandran Vignesh , Thomas Tinu , Maria Ann , Schrader Kasmintan A. , Moore Raymond , Hu Chunling , Wubbenhorst Brad , Wenz Brandon M. , D'Andrea Kurt , Domchek Susan M. , Robson Mark E. , Peterlongo Paulo , Radice Paolo , Ford James M. , Garber Judy E. , Szabo Csilla , Offit Kenneth , Nathanson Katherine L. , Couch Fergus J. , Weitzel Jeffrey N. 
Published: July 2017

Abstract
A better understanding of gene-specific risks for development of breast cancer will lead to improved screening, prevention, and therapeutic strategies for individuals identified to carry germline mutations. We performed targeted massively-parallel sequencing to identify mutations and large genomic rearrangements in 26 known or proposed breast cancer susceptibility genes in 2134 BRCA-negative women with familial breast cancer (FBC). A case-control analysis was performed comparing the frequency of internally classified mutations identified in FBC cases to that in non-Finnish European controls from the Exome Aggregation Consortium (ExAC) excluding samples from The Cancer Genome Atlas. Including large genomic rearrangements, mutations were identified in 8.2% of FBC cases compared to 6.2% of ExAC controls, including mutations in high-penetrance genes (0.6% in cases vs. 0.1% in controls), moderate-penetrance genes (3.7% vs 1.7%), and seven cases with two mutations (0.3%). The remainder of FBC cases and ExAC controls had mutations in proposed breast cancer genes (1.6% of cases vs 2.4% of controls), Lynch syndrome genes (0.5% vs. 0.5%) or were heterozygous MUTYH carriers (1.5% vs. 1.5%). Case-control analysis demonstrated significant associations with FBC for ATM, PALB2, and TP53 mutations (OR&gt;3.0, p&lt;10-4), BARD1 mutations (OR=3.2, p=0.012), and CHEK2 truncating mutations (OR=1.6, p=0.041). Our results therefore demonstrate that only approximately 4% of BRCA1/2 negative FBC patients have mutations in genes definitively associated with breast cancer at this time. Large case-control studies are needed to fully evaluate the breast cancer risks associated with moderate penetrance and proposed breast cancer susceptibility genes.
Citation Format: Kara N. Maxwell, Thomas Paul Slavin, Jenna M. Lilyquist, Joseph Vijai, Susan L. Neuhausen, Steven N. Hart, Vignesh Ravichandran, Tinu Thomas, Ann Maria, Kasmintan A. Schrader, Raymond Moore, Chunling Hu, Brad Wubbenhorst, Brandon M. Wenz, Kurt D'Andrea, Susan M. Domchek, Mark E. Robson, Paulo Peterlongo, Paolo Radice, James M. Ford, Judy E. Garber, Csilla Szabo, Kenneth Offit, Katherine L. Nathanson, Fergus J. Couch, Jeffrey N. Weitzel. Risks of familial breast cancer associated with known and proposed breast cancer susceptibility genes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4265. doi:10.1158/1538-7445.AM2017-4265
Abstract 427: A path towards determining tumor mutation burden and identifying neoantigens using next-generation sequencing (NGS)
Authors: So Alex , Kaplan Shannon , Wang Nai-yu , Zhang Shile , Wise Aaron , Kruglyak Kristina , Gutekunst Karen 
Published: July 2017

Abstract
Introduction: The recent clinical demonstrations that cancer immunotherapy is effective for some patients, but not others has led to widespread interest in identifying cancer genetic factors that can predict positive response. Importantly, it has been shown by various studies that tumor mutation burden (TMB) and predicted neoantigen load correlate with patient response to checkpoint inhibitors. This project aims to develop a clinical next-generation sequencing (NGS) assay that utilizes TMB and neoantigen information to guide cancer immunotherapy selection.
Experimental Procedures: Whole exome sequencing (WES) and whole transcriptome sequencing (WTS) libraries were generated using Illumina’s TruSeq® Exome and RNA Access library preparation kits, respectively. The samples were pair-end sequenced (2x75bp) using HiSeq® 2000 and 2500 instruments.
Data Summary: Here, we demonstrate a workflow using tumor/normal WES and tumor-only WTS to determine expressed TMB. Using the WES data, we were also able to accurately identify human leukocyte antigen (HLA) major histocompatibility complex (MHC) Class I genes at four-digit resolution. We then identified putative neoantigens, defined as peptides with mutated amino acids, that were expressed in the tumor samples and predicted to bind to the respective HLA sequences. In addition, as a path towards developing a clinical assay for TMB and neoantigen determination, we tested the ability of reagents developed for Illumina’s Trusight® Tumor 170 panel to be used for an exome panel. With workflow modifications, we achieved comparable quality of sequencing metrics as compared to the TruSeq® Exome kit.
Conclusion: Our data demonstrate a path towards developing a clinical assay that can be used to assess TMB and neoantigen candidates.
Citation Format: Alex So, Shannon Kaplan, Nai-yu Wang, Shile Zhang, Aaron Wise, Kristina Kruglyak, Karen Gutekunst. A path towards determining tumor mutation burden and identifying neoantigens using next-generation sequencing (NGS) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 427. doi:10.1158/1538-7445.AM2017-427
Abstract 4270: Family history in first degree relatives and risk of gastric cancer in the alpha-tocopherol, beta-carotene cancer prevention study
Authors: Song Minkyo , Camargo Maria Constanza , Weinstein Stephanie J. , Albanes Demetrius , Rabkin Charles S. 
Published: July 2017

Abstract
Background: Studies of the familial associations of gastric cancer risk have largely been limited to case-control approaches which are susceptible to recall bias and cannot distinguish temporality. Furthermore, associations with family history could be explained by shared exposure to Helicobacter pylori infection, the most important environmental risk factor for gastric cancer. Notably, the risks of early onset disease and diffuse-type tumors are thought to have a greater genetic component. We therefore examined in a prospective study the associations of gastric cancer risk with history of gastric cancer in first degree relatives, controlling for H. pylori infection.
Methods: We selected 405 incident gastric cancer cases and 4,129 controls with known H. pylori serology status from the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study among male smokers aged 50-69 at baseline. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using logistic regression with adjustment for H. pylori and other potential confounders. All statistical tests were two-sided.
Results: Family history of gastric cancer was associated with increased risk (OR=1.84, 95% CI=1.32-2.58). The association appeared stronger with gastric cancer in siblings (OR=2.87, 95% CI=1.64-5.03) than with gastric cancer in parents (OR=1.53, 95% CI=1.05-2.24). Distinguishing cases by anatomic subsite, the family history association was significant for noncardia gastric cancer (n=305; OR=2.15, 95% CI=1.50-3.07), but not for cardia cancer (n=100; OR=1.25, 95% CI=0.63-2.49). With regard to histological subtype, family history was significantly associated with both diffuse-type (n=90; OR=2.12, 95% CI=1.10-4.12) and intestinal-type (n=153; OR=1.70, 95% CI=1.02-2.83) gastric cancer. In age-specific analyses, the association with family history was strongest in the youngest age-group at baseline 50-54 years (OR=3.42, 95% CI=1.85-6.30) and absent in the oldest age group 65-69 years (OR=0.85, 95% CI=0.28-2.58).
Conclusion: The results suggest that certain subtypes of sporadic gastric cancer are strongly associated with family history of gastric cancer. These associations do not appear to be explained by the associations with H. pylori infection.
Citation Format: Minkyo Song, Maria Constanza Camargo, Stephanie J. Weinstein, Demetrius Albanes, Charles S. Rabkin. Family history in first degree relatives and risk of gastric cancer in the alpha-tocopherol, beta-carotene cancer prevention study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4270. doi:10.1158/1538-7445.AM2017-4270