bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2521: Race specific differences in DNA damage repair dysregulation in breast cancer and association with outcome
Authors: Mazumder Aloran , Jimenez Athena , Ellsworth Rachel , Freedland Stephen , George Sophia , Bainbridge Matthew , Haricharan Svasti 
Published: July 2021

Abstract
African American (AA) estrogen receptor positive (ER+) breast cancer patients have worse outcomes than Caucasian Americans (CA) being 42 % more likely to die from the disease. However, AAs are severely underrepresented in currently available datasets of patient tumors, which precludes comprehensive approaches to identify race-specific molecular drivers of these poor outcomes. Endocrine therapy (ET) is the first line standard of care for ER+ breast cancer. Nevertheless, 1 in 4 patients develop ET resistance. Specific DNA damage/repair (DDR) defects have been shown to associate with poor outcome in CA patients, and to induce ET resistance. Whether these or other DDR defects contribute to poor outcomes observed in AA patients remains unknown. For the purpose of this investigation, we assessed the DDR dysregulation landscape of AA ER+ tumors using three independent tumor datasets (1) GSE78958 (2) GSE18229 (3) The Cancer Genome Atlas (TCGA) and two normal breast datasets (1) GSE43973 (2) GSE50939. This analysis identified a distinct set of AA ER+ tumors with simultaneous dysregulation of genes from multiple DDR pathways, rarely seen in CA tumors. This simultaneous dysregulation also associated with worse patient outcomes in all three datasets analyzed. This work constitutes the first systematic analysis of race-specific DDR dysregulation in ER+ breast cancer, and identifies DDR as a potential predictive biomarker for worse outcome seen in AA patients.
Citation Format: Aloran Mazumder, Athena Jimenez, Rachel Ellsworth, Stephen Freedland, Sophia George, Matthew Bainbridge, Svasti Haricharan. Race specific differences in DNA damage repair dysregulation in breast cancer and association with outcome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2521.
Abstract 2540: Belief in research, religious coping, and willingness to participate in clinical trials among African Americans with hematologic malignancies: a pilot study
Authors: Petty Marjorie 
Published: July 2021

Abstract
Purpose: The purpose of the proposed prospective cohort, pilot study is to recruit 30 AAs with hematologic malignancies to determine if a relationship exists between belief in research and willingness to participate in cancer clinical trials. The secondary objective is to determine whether religious coping moderates the effect of belief in research on the relationship between willingness to participate.
Description: African Americans (AAs) are disproportionately affected by certain types of hematologic malignancies, yet despite the efforts of investigators, they remain grossly underrepresented in cancer clinical trials. Few studies have evaluated the underrepresentation in clinical trials in this subgroup, while studies evaluating the same problem in AAs with solid tumors is well documented. A known barrier to clinical trial enrollment is knowledge of clinical trials; however, knowledge does not necessarily mean one will participate. One has also to believe and be willing to participate in clinical trials. Even so, it is unknown if a relationship exists between belief in research and willingness to participate in clinical trials in AAs with hematologic malignancies. Similarly, it is unknown if religious coping influences the possible association between belief in research and willingness to participate in AAs with hematologic malignancies. Due to sparse literature showing the connection of the concepts within this subset of AAs, research investigating the relationship between belief in research and willingness to participate is warranted.
Summary: Data will be captured at one time using the validated Brief Religious Coping Scale and researcher generated questions that address belief in research and willingness to participate in cancer clinical trials.
Conclusion: Findings will help in the design of future studies and the feasibility of recruiting AAs with hematologic malignancies.
Citation Format: Marjorie Petty. Belief in research, religious coping, and willingness to participate in clinical trials among African Americans with hematologic malignancies: a pilot study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2540.
Abstract 2556: The somatic variant of HLRCC, an unrecognized type of RCC
Authors: Merino Maria J. , Dikoglu Esra , Gurram Sandeep , Linehan Marston , Srinivasan Ramaprasad 
Published: July 2021

Abstract
Background: Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a hereditary cancer syndrome where affected individuals are predisposed to the development of multiple leiomyomas of the skin and uterus and aggressive forms of kidney cancer. Affected individuals harbor a germline heterozygous loss-of-function mutation of the fumarate hydratase (FH) gene. Diagnosis of these tumors is done on clinical, morphologic and immunohistochemical (IHC) determination of negative staining for FH and genetic testing considered the gold standard. Somatic mutations in HLRCC RCC are not well recognized, and the morphologic features of tumors associated with the somatically mutated tumors has not been described. We report the clinical, morphologically and genetic findings of 7 patients with HLRCC and somatic mutations.
Design: Clinicopathologic correlation was done in all cases. All patients (4 males and 3 females) denied family history of kidney cancer or skin lesions. Age range was from 27 to 77. All patients had metastatic disease when accepted for protocol. Genetic testing was performed in all cases and IHC for FH when material was available.
Results: The genetic testing was negative for a germline mutation in all cases; however a pathogenic somatic mutation was found in all of them. Some of the somatic mutations included two copy deletion of 1q43, multiple break points on chromosome 1, and loss of heterozygosity. Morphologically the predominant pattern was extensive dense tubular formation with small tubules lined by clear or eosinophilic cells in which some nuclear features suggestive of HLRCC were identified (4 cases) the other cases showed cystic and papillary features. The diagnosis of HLRCC was suggested and FH performed with negative results.
Conclusion: Pathologists need to be aware that HLRCC with somatic and no germline mutations may occur more frequently than suspected and that a negative family history is frequently obtained. Morphology is helpful. However, staining for FH with negative results should be suspicious of HLRCC and genetic testing repeated considering the possibility of a somatic mutation, so proper diagnosis is made, and patients receive proper therapies.
Citation Format: Maria J. Merino, Esra Dikoglu, Sandeep Gurram, Marston Linehan, Ramaprasad Srinivasan. The somatic variant of HLRCC, an unrecognized type of RCC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2556.
Abstract 2561: Tumorigenic and metabolomic impacts of adipose-derived monocyte chemotactic protein-1 in a model of obesity-enhanced, male breast cancer
Authors: Yan Lin , Sundaram Sneha , Rust Bret M. , Picklo Matthew J. , Bukowski Michael R. 
Published: July 2021

Abstract
Breast cancer is a rare but aggressive disease in men. Approximately, 90% of all breast cancer in men are invasive carcinomas, 25% of which have distant metastasis at the time of clinical presentation. Obesity is a risk factor for breast cancer. Monocyte chemotactic protein-1 (MCP-1) is an adipose-derived cytokine whose concentrations are elevated by obesity. This study tested the hypothesis that adipose-derived MCP-1 contributes to male breast cancer. In a 2x2 design, male MMTV-PyMT mice with or without adipose specific Mcp-1 knockdown [designated as Mcp-1-/- or wild-type (WT)] were fed the standard AIN93G diet or an obesogenic, high-fat diet (HFD) for 25 weeks. The AIN93G diet and HFD contained 16% and 45% of energy from soybean oil, respectively. Mcp-1-/- mice had lower adipose Mcp-1 expression than WT mice. Adipose Mcp-1 deficiency reduced plasma concentrations of MCP-1 in mice fed the HFD. Mice fed the HFD had a greater tumor progression rate than mice fed the AIN93G diet (4679% vs 2430%), regardless of genotype. Mcp-1-/- mice, compared to WT mice, had a longer tumor latency (25.2 weeks vs 18.0 weeks) and lower tumor incidence (19% vs 56%), tumor progression rate (2317% vs 4792%), and tumor weights (0.23 g vs 0.64 g). Metabolomic analysis of plasma identified 87 metabolites, 56 of which differed among the four groups, including 24 that differed between the diets and 22 that differed between the genotypes. Sparse partial least squares-discriminant analysis identified 10 major metabolites that were altered the most among the four groups. These included amino acids (alanine, isoleucine, leucine, phenylalanine, threonine, and valine) and carbohydrate metabolites (fumaric acid, glucuronic acid, hexuronic acid, and malic acid). The integrated pathway analysis of the 87 identified metabolites showed that protein biosynthesis and carbohydrate metabolism pathways are the most disturbed in MMTV-PyMT mice. In conclusion, adipose-derived MCP-1 contributes to mammary tumorigenesis and alters metabolism in male MMTV-PyMT mice.
Citation Format: Lin Yan, Sneha Sundaram, Bret M. Rust, Matthew J. Picklo, Michael R. Bukowski. Tumorigenic and metabolomic impacts of adipose-derived monocyte chemotactic protein-1 in a model of obesity-enhanced, male breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2561.
Abstract 2566: The potential role of licorice and its bioactive compounds in promoting a tumor preventive environment in the postmenopausal breast
Authors: Hajirahimkhan Atieh , Howell Caitlin , Chen Shao-Nong , Clare Susan E. , Pauli Guido F. , Bolton Judy L. , Dietz Birgit M. , Khan Seema A. 
Published: July 2021

Abstract
Introduction: our purpose was to define if licorice and its main bioactive compounds can suppress aromatase expression/activity and Nrf2 dependent detoxification pathways in the postmenopausal breast. This chemopreventive potential has not previously been reported in preclinical models of high-risk postmenopausal breast.
Methods: Inhibition of aromatase activity by three licorice extracts (Glycyrrhiza species), and their bioactive compounds, (liquiritigenin; LigF, isoliquiritigenin; LigC, 8-prenylapigenin; 8-PA, and licochalcone A; LicA) were evaluated fluorometrically, using aromatase supersomes. Computational docking was performed to assess the binding of the bioactive compounds to the binding pocket of aromatase crystal structure compared to the known aromatase inhibitors, letrozole (non-steroidal) and exemestane (steroidal). Using qPCR, the effects of treatments on the expression of aromatase (CYP19A1) mRNA and Nrf2 dependent detoxification enzyme NADPH:quinone oxidoreductase 1 (NQO1) in breast microstructures obtained from high risk postmenopausal women were evaluated.
Results: Among the three medicinally used licorice species, Glycyrrhiza inflata (GI) showed the highest aromatase inhibitory potency (IC50 ≈ 1 µg/mL). Licorice phytoestrogens, LigF (400 nM or 0.1 µg/mL), and 8-PA (IC50 ≈ 590 nM or 0.2 µg/mL) exhibited the highest potency compared to the other tested licorice compounds. Computational docking suggested that these phytoestrogens bind to the aromatase binding pocket like the aromatase inhibitor, letrozole. This effect was not observed with non-estrogenic bioactive compounds of licorice, LigC and LicA (specific to GI). In breast microstructures obtained from high risk postmenopausal women, expression of aromatase mRNA was suppressed by GI (30%, P &lt; 0.05), LigF (20%, P &lt; 0.05), and LicA (45%, P &lt; 0.05), while the expression of NQO1 mRNA was enhanced by LicA (200%, P &lt; 0.0001).
Conclusions: Licorice species, and their bioactive compounds inhibited aromatase activity in vitro. In the breast microstructures, GI, its compounds LigF and LicA suppressed aromatase expression, and LicA enhanced NQO1 induction, significantly. Further studies will further elucidate the potential of these natural products for promoting a breast tumor preventive environment in postmenopausal women.
Citation Format: Atieh Hajirahimkhan, Caitlin Howell, Shao-Nong Chen, Susan E. Clare, Guido F. Pauli, Judy L. Bolton, Birgit M. Dietz, Seema A. Khan. The potential role of licorice and its bioactive compounds in promoting a tumor preventive environment in the postmenopausal breast [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2566.
Abstract 2602: Leveraging cell-free methylome markers for early cancer detection
Authors: Cheng Nicholas , Skead Kimberly , Soave David , Meng Jocelyn , Gbeha Elias , Lungu Ilinca , Lam Bernard , Bratman Scott , De Carvalho Daniel , Awadalla Philip 
Published: July 2021

Abstract
Cancer survival rates are significantly improved when detected at early stages, particularly when the tumor is still localized to the tissue of origin. However, effective screening tools for early cancer detection is currently limited to a subset of cancer types. The early development of human malignancies are difficult to observe as cancers are often detected once it becomes symptomatic, as such many cancer biomarker and evolution studies to date have primarily examined the genomics from solid tumor or liquid biopsies following a diagnosis. Investigating early tumor evolution in the pre-diagnosis context could allow us to better understand how to prevent or detect cancers in the earliest stage when survival rates are significantly higher, however this requires application of new technologies to biologics collected prior to a cancer diagnosis. Here, we leverage blood samples collected from participants in the Canadian Partnership for Tomorrow Project (CPTP), a longitudinal population cohort, prior to the onset of a cancer. Specifically, we utilize hybrid capture approaches to enrich for and characterize early mutations and methylation changes in circulating tumor DNA (ctDNA) of pre-cancer plasma samples collected from patients several months to years prior to clinical diagnosis. Here, we identify the earliest detectability of aberrant genetic and epigenetic events in ctDNA and describe the molecular evolution of these events at various stages prior to clinical detection of cancers. Further, we develop molecular biomarkers and implement machine learning tools to classify individuals with early cancers, and to develop risk scores from survival analyses predictive of cancer development up to 5 years prior to diagnosis. In our current study, we focus specifically on breast, prostate, lung and pancreatic cancer cases, and are extending this to pan-cancer applications in subsequent studies.
Citation Format: Nicholas Cheng, Kimberly Skead, David Soave, Jocelyn Meng, Elias Gbeha, Ilinca Lungu, Bernard Lam, Scott Bratman, Daniel De Carvalho, Philip Awadalla. Leveraging cell-free methylome markers for early cancer detection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2602.
Abstract 2623: Investigation into factors influencing probability of success in oncology clinical trials and trends over time
Authors: Hinrichs Mary Jane , Chaudhuri Shomesh E. , Bowden Robert , Lo Andrew W. , Jenkins David W. 
Published: July 2021

Abstract
The regulatory approval process for new therapies in oncology involves costly clinical trials that can span multiple years and historically have had a low probability of success. To derive estimates of the probability of success and other related risk characteristics in oncology clinical trials, we searched Informa Pharma Intelligence's Trialtrove and Pharmaprojects databases for oncology-specific drug-indication programs between 2001 and 2020. In total, we identified 10,083 oncology-specific drug-indication programs, which included 2,800 therapeutic agents (excluding biosimilars) tested across 98 indications. The features we considered included indication and indication group, clinical phase, follow-on indication status, presence and type of patient selection biomarker, drug modality, and accelerated approval status. In several cases, clinical success rates were higher than the benchmark oncology historical average of the phase 1 to approval success rate of 4.1% found in our sample set. For example, the use of pre-selection biomarkers in early clinical development was associated with a greater than two-fold increase in probability of approval from phase 1. Moreover, drugs with prior approvals in another indication were more than three times more likely to be successful from phase 1 than a candidate targeting a novel mechanism. In addition, we found that monoclonal antibodies were numerically more successful than other modalities in the historical data, while oncolytic viruses, vaccines, and bispecific antibodies have been less successful. In all cases, concomitant with the emergence of genomic technologies, an improved scientific understanding of cancer biology, and an evolving regulatory environment that includes a higher number of accelerated approvals, success rates in oncology have improved during the time period of this analysis and particularly in the past 5 years.
Citation Format: Mary Jane Hinrichs, Shomesh E. Chaudhuri, Robert Bowden, Andrew W. Lo, David W. Jenkins. Investigation into factors influencing probability of success in oncology clinical trials and trends over time [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2623.
Abstract 2626: The effectiveness of healthcare professional training on the legal issues impacting individuals diagnosed with cancer to improve patient quality of life
Authors: Morales Joanna , Bryant Monica , Ward Madison McMahon 
Published: July 2021

Abstract
A cancer diagnosis may carry with it a variety of legal issues, including insurance coverage, government benefits, and consumer rights. These legal issues can cause people unnecessary worry, confusion, and stress, and can be overwhelming. The Insurance and Finance Intensive is focused on providing healthcare professionals tools to proactively identify the presence of cancer-related legal, health insurance, and financial issues facing their patients. Additionally, the training helps health care professionals to offer referrals to appropriate legal and related resources, once those issues are identified. Oncology healthcare professionals participated in an eight-hour comprehensive training. Attendees were provided with substantive information about cancer-related legal issues, such as identifying health insurance options, navigating disability insurance and appeals, and managing finances. A follow-up survey was sent to all past intensive attendees to measure the effectiveness of the training and to address any lingering questions and difficult case studies. Ninety-four percent of survey respondents strongly agreed or agreed that the information provided by the training helped them reduce the stress and anxiety of their patients and their families. Ninety-two percent of survey respondents strongly agreed or agreed that the information provided by the training improved the quality of life of their patients and their families. The Insurance & Finance Intensive successfully provided health care professionals with valuable information on the practical and legal issues that impact individuals diagnosed with cancer. It is recommended that more healthcare professionals participate in this training to improve the quality of life of their patients beyond diagnosis.
Citation Format: Joanna Morales, Monica Bryant, Madison McMahon Ward. The effectiveness of healthcare professional training on the legal issues impacting individuals diagnosed with cancer to improve patient quality of life [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2626.
Abstract 265: Evaluating variation in drug efficacy endpoints in a syngeneic mouse model (CT26.WT) under immune checkpoint blockade
Authors: Mao Binchen , Guo Sheng , Ouyang Davy , Li Henry 
Published: July 2021

Abstract
INTRODUCTION: Preclinical research into immune checkpoint blockade (ICB) requires in vivo models with fully functional immunity. Syngeneic mouse models are homografts derived by transplanting immortalized mouse cancer cell lines or tumor tissues into strain-matched mouse hosts, and are well suited for evaluating the efficacy of new immunotherapies due to retaining an intact mouse immune system. Tumor growth inhibition (TGI) is widely used to characterize drug efficacy, however, a considerable amount of heterogeneity among TGI is often observed for a given ICB treatment in the same syngeneic mouse model. It is of vital importance to understand the source of such variation. The present study sets out to systematically investigate the variation of TGI for ICB treatment in syngeneic mouse models, using tumor growth data of anti-PD-1 treatment in the CT26.WT syngeneic mouse model for 27 independent studies.
METHODS: For each study, we calculated TGI and median area under curve (AUC) ratio on the corresponding study day when tumor volume data was collected. We utilized standard deviation and inter quantile range to quantify the variation. We evaluated the relationship between TGI and the corresponding day, and also compared the variation between TGI and median AUC ratio. Furthermore, to better understand the source of drug efficacy variation, we utilized a Bayesian multilevel model to quantify the amount of tumor growth variation at both the study and mouse level.
RESULTS: We found that TGI variation was much higher at earlier stages of studies. In contrast, the median AUC ratio showed smaller variation across the duration of each study than TGI for the majority of studies. Additionally, we found neither TGI nor median AUC ratio had significant correlation with the number of mice used in the study. Based on a Bayesian multilevel model, we observed that drug efficacy had larger variation on the mouse level (i.e. within a study), than variation on the study level (i.e. observed between studies), which could indicate heterogeneity of the tumor microenvironment (e.g. TILs) among mice play a major role in the variation of ICB treatment efficacy among studies.
CONCLUSIONS: Response to ICB treatment among mice of the same syngeneic model is inherently heterogeneous. TGI of later time points should be favored to reduce variation, and generally median AUC Ratio is more stable than TGI.
Citation Format: Binchen Mao, Sheng Guo, Davy Ouyang, Henry Li. Evaluating variation in drug efficacy endpoints in a syngeneic mouse model (CT26.WT) under immune checkpoint blockade [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 265.