bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P3-06-02: Exosomes produced by adipocytes induce EMT, immune exhaustion and tumor metastasis, in both in vivo and in vitro models of TNBC
Authors: Qiu Yuhan , Ross Conor , Jafari Naser , Kolla Manohar , Llevenes Pablo , Ennis Christina , Mazzeo Carla S , Mahdaviani Kiana , Ko Naomi Y , Denis Gerald V 
Published: March 2022

Abstract
Type 2 Diabetes (T2D) is a chronic inflammatory disease characterized by inflamed adipose tissue. Patients with triple negative breast cancer (TNBC) and comorbid T2D have higher risk of metastasis and shorter survival. However, mechanisms that couple T2D to TNBC outcomes are unknown. Here we hypothesize that exosomes, small vesicles secreted by tumor microenvironment breast adipocytes, drive epithelial-to-mesenchymal transition (EMT) in TNBC, immune exhaustion and metastasis via Ampk-Akt signaling.Methods: Exosomes were purified from conditioned media of 3T3-L1 mature adipocytes that were insulin-sensitive (IS) or insulin-resistant (IR), then characterized and quantified by NanoSight and surface markers, CD63. Murine 4T1 cells, a TNBC model, were treated with exosomes in vitro (3 days). To establish 3D organoids, 4T1 spheroids were treated with exosomes and embedded in Matrigel. For in vivo models, mammary fat pads of BALB/c mice were injected with 4T1 cells treated with IS vs IR exosomes. 4T1 tumors were harvested and mRNA extracted for qPCR, RNAseq, and Ingenuity Pathway Analysis. Metastatic sites in lung and liver were visualized by H&E staining and clonogenic assay. Immune exhaustion markers of tumor infiltrated lymphocytes (TILs) were measured by flow cytometry. Results: In 4T1 cells treated with IR exosomes, EMT was upregulated and PD-L1 expression increased. Tumor-bearing mice exhibited metastasis in exosome-treated groups, visualized by microscopy and clonogenic assay. Immune exhaustion markers showed modified expression in TILs from exosome-treated groups. RNA-seq analysis revealed differences among exosome-treated groups that suggest dysregulated Ampk-Akt pathways.Conclusion: Exosomes from IR adipocytes modify the tumor microenvironment, increase EMT and immune exhaustion markers on tumor cells and TILs, and promote metastasis to distant organs through Ampk-Akt. Metabolic diseases such as T2D reshape the TNBC tumor microenvironment, promoting metastasis and decreasing survival. Clearly, TNBC patients with T2D should be more closely monitored for metastasis than metabolically normal patients, with metabolic medications considered.
Citation Format: Yuhan Qiu, Conor Ross, Naser Jafari, Manohar Kolla, Pablo Llevenes, Christina Ennis, Carla S Mazzeo, Kiana Mahdaviani, Naomi Y Ko, Gerald V Denis. Exosomes produced by adipocytes induce EMT, immune exhaustion and tumor metastasis, in both in vivo and in vitro models of TNBC [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-06-02.
Abstract P3-06-07: Glutathione peroxidase 8 (GPX8) as a novel therapeutic target in triple negative breast cancer
Authors: Khatib Anees 
Published: March 2022

Abstract
Negative Breast Cancer (TNBC) accounts about 15% of the breast cancer incidence worldwide. While molecular subtypes which express estrogen and progesterone receptors (ER, PR) and the human epidermal growth factor receptor 2 (HER2, ERBB2) are favorable, TNBC is more associated with patient poor prognosis. GPX8 is a poorly characterized enzyme that resides in the endoplasmic reticulum, is an essential regulator of tumor aggressiveness. We found that GPX8 expression was induced by the epithelial-mesenchymal transition (EMT) program. Moreover, in breast cancer patients, GPX8 expression significantly correlated with known mesenchymal markers and poor prognosis. Strikingly, GPX8 knockout in TNBC mesenchymal-like cells (MDA-MB-231) resulted in an epithelial-like morphology, down-regulation of EMT characteristics, and loss of cancer stemness features. In addition, GPX8 knockout significantly delayed tumor initiation and decreased its growth rate in mice. We found that these GPX8 loss-dependent phenotypes were accompanied by the repression of crucial autocrine factors, in particular, interleukin-6 (IL-6). In these cells, IL-6 bound to the soluble receptor (sIL6R), stimulating the JAK/STAT3 signaling pathway by IL-6 trans-signaling mechanisms, so promoting cancer aggressiveness. We observed that in GPX8 knockout cells, this signaling mechanism was impaired as sIL6R failed to activate the JAK/STAT3 signaling pathway. Altogether, we present the GPX8/IL-6/STAT3 axis as a metabolic-inflammatory pathway that acts as a robust regulator of breast cancer cell aggressiveness. These findings motivated us to suggest GPX8 as a novel therapeutic target in TNBC.
Citation Format: Anees Khatib. Glutathione peroxidase 8 (GPX8) as a novel therapeutic target in triple negative breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-06-07.
Abstract P3-12-17: Breast cancer treatment related survival gains in the African breast cancer - Disparities in outcomes study
Authors: Foerster Milena , Kantelhardt Eva , Boucheron Pauline , dos-Santos-Silva Isabel , McCormack Valerie ,   the ABC-DO study team
Published: March 2022

Abstract
Background: Breast cancer (BC) survival in Low and Middle Income Countries (LMICs), and particularly Sub Saharan Africa (SSA), is low and incidence rates are increasing. Accordingly, an almost 90% increase in annual BC mortality is projected to occur until 2040. The WHO Breast Cancer Global Initiative named comprehensive breast cancer treatment as one of three main pillars to reduce BC mortality. Here, we present the urgently needed up-to-date benchmark estimates of treatment effects on BC survival in SSA using data from the African Breast Cancer Disparities in Outcomes (ABC-DO) study.Methods: Since 2014 the hospital-recruited ABC-DO cohort follows-up women diagnosed with BC in five SSA countries. Socio-demographic, diagnostic, treatment and mortality data were obtained from medical records and via three-monthly follow-up calls with the patient. Cox proportional hazard models were fitted to estimate 5-year overall survival related to treatment initiation (surgery or systemic therapy) and treatment completion as time varying variates (surgery and systemic therapy completed) stratified by country and ethnicity and separate for localised and regional tumours. All models were adjusted for age, tumour grade, tumour size, node positivity, HIV status, and socioeconomic status. Results: Of 1699 ABC-DO women with invasive non-metastatic BC, 89% initiated BC treatment (from 72% in Nigeria to 100% in South African white women). Potentially curative treatment (surgery plus systemic therapy) was initiated by 63%, 22% initiated systemic treatment and 5 % only surgery. Initiated systemic therapy was completed by 49% of patients (from 16% in Nigeria to 70 % in South African black women). Median time to first treatment was 1.4 (IQR: 0.8–3) months and differed between countries (from 1.1 (0.6–1.7) in Namibian non-black to 3 (1.5–4.3) in Uganda). After 5 years, 49% (0.44 (CI: 0.31 – 0.62) ) of women initiating any treatment and 59% (0.39 (0.27 – 0.56) of women receiving surgery and initiating systemic treatment were still alive compared to 20% of women receiving no treatment. Conclusion: Timely and comprehensive BC treatment are needed to increase the very low survival rates in SSA.
Citation Format: Milena Foerster, Eva Kantelhardt, MD, Pauline Boucheron, Isabel dos-Santos-Silva, PhD, Valerie McCormack, the ABC-DO study team. Breast cancer treatment related survival gains in the African breast cancer - Disparities in outcomes study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-12-17.
Abstract P3-14-10: Breast cancer patterns, behavior and survival among American Indians in the west north central region and the other regions of the U.S.
Authors: Gaba Anu G , Cao Li , Renfrew Rebecca , Witte Deann , Wernisch Janet , Lutkemeier Denise , Egland Kristi , Crosby Ross 
Published: March 2022

Abstract
Purpose: American Indians (AIs) constitute the single largest racial minority in North Dakota and South Dakota. There are no studies looking at what sociodemographic or biological factors may play a role in affecting outcomes and mortality of breast cancer (BC) among AIs in the United States. Our study compared the BC patterns, behavior, and survival of AIs living in the West North Central Region (WNCR) of the U.S (which includes ND, SD, MN, NE, IO, KS, MO) to the AI BC patients in the remainder of the country. Methods: We used the records of all AI BC patients diagnosed between the years 2004-2016 from The National Cancer Database participant user files. All analyses were conducted using SPSS software (version 25). Results: Records were available for 6,466 AI BC patients, 798 were in the WNCR. There was no difference between WNCR and other regions in the stage distribution, mean age at diagnosis, morphology, hormonal/HER2 status, tumor size, lymph node status, or second cancers. The WNCR patients had less private insurance, lived in zip codes with lower median income, had more co-morbidities, and traveled longer distances for care (p&lt;0.001 for each). They had higher grade cancers (p&lt;0.001) at diagnosis. The WNCR patients were less likely to have received radiation therapy (p=0.015) but more likely to have received chemotherapy (p&lt;0.001) and hormonal therapy (p=0.009) and had longer inpatient stay days after surgery (p&lt;0.001). Time to first treatment and first treatment within 90 days (88.0% vs. 79.7%, p&lt;0.001) was significantly better in the WNCR than in other regions of the country. Five year mortality rate was higher (16.3% vs. 11.1%, p&lt;0.001) and cumulative survival was lower (p&lt;0.001) in the WNCR as compared to AIs in other regions of the country. Univariate/multivariate analysis failed to identify variables that could explain the differences in 5 year mortality or cumulative survival between WNCR and other regions. Conclusion:AIs with BC in the WNCR had worse 5 year mortality and cumulative survival as compared to AIs in other regions in the US. Our analysis could not identify variables that explained the differences in mortality or cumulative survival between WNCR and other regions.
Citation Format: Anu G Gaba, Li Cao, Rebecca Renfrew, Deann Witte, Janet Wernisch, Denise Lutkemeier, Kristi Egland, Ross Crosby. Breast cancer patterns, behavior and survival among American Indians in the west north central region and the other regions of the U.S. [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-14-10.
Abstract P3-14-20: Racial and ethnic groups have different clustering of variants of uncertain significance
Authors: Beitsch Peter , Wernecke Chloe , Bontempo Kelly , Bentley Brenna , Graham Maureen , Whitworth Pat , Patel Rakesh 
Published: March 2022

Abstract
Background:Racial/ethnic disparities in minority access to genetic testing have perpetuated a higher likelihood of identifying an uncertain result in minority populations. Methods:Patient data was obtained from the Informed Genetics Annotated Patient Registry (iGAP), an IRB-approved multi-center longitudinal, observational study designed to capture genetic and genomic test results and their utilization and impact on treatment practices and outcomes. Patients self-declare race/ethnicity. Genetic panels contained between 1 and 148 genes and variant classification was determined by the performing genetic testing companies and reported as negative, variant of uncertain significance (VUS), likely-pathogenic, or pathogenic. Descriptive statistics were used to assess and compare data of these populations and germline genetic testing results indicating variant of uncertain significance. Results:Hispanic and African American patients had approximately twice as many uncertain results (VUS) compared to Caucasian patients for all cancer genes examined. Conclusions:Variant adjudication has disproportionately sorted out more uncertain results in Caucasians than Hispanics and African Americans. This leads to greater uncertainty in post-test counseling for these groups and should be a focus for lab testing companies going forward.
Citation Format: Peter Beitsch, Chloe Wernecke, Kelly Bontempo, Brenna Bentley, Maureen Graham, Pat Whitworth, Rakesh Patel. Racial and ethnic groups have different clustering of variants of uncertain significance [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-14-20.
Abstract P3-16-02: Enhancing impact and efficiency of financial support for cancer through use of AI: A nascent initiative of Indian cancer society
Authors: Vora Tushar , Khanna Nehal , Gokarn Anant , Rawat Ann , Ramarajan Naresh , Srivastava Gitika , Thorat Usha 
Published: March 2022

Abstract
Background: Since 2011, Indian Cancer Society-Cancer Cure Fund (ICS-CCF), established through donations of mutual fund dividends, has funded $27 million in treatment costs for 9800 underprivileged patients. For governance, a Due Diligence Team (DDT) of cancer experts from academic tertiary centers reviewed every planned treatment and authorized covering the treatment costs for evidence-based care. Since expert time is scarce, in 2019, ICS-CCF introduced NAVYA AI (AI) system to scale the prior authorization operation. AI is a clinically validated system that matches clinical data with evidence and expert recommended treatment options. The system can adapt to institutional guidelines such as ICS-CCF authorization criteria on published survival rates. In this prospective study, we explore application of AI in prior authorization, by assessing concordance with DDT expert decisions and potential time savings. Methods: Clinical data of beneficiaries were input in AI and if the output treatment options matched the planned treatment, the application was authorized, otherwise rejected. If AI did not output a decision, the application was deferred to DDT. Concordance between AI and DDT decisions, and DDT time spent on deferred applications, weremeasured. Results: From April 22nd, 2020 to June 9th, 2021, 1994 beneficiary applications were simultaneously reviewed by AI and DDT, of which 601 (30%) were breast cancer patients. AI “authorized” (1563/1994) or “rejected” (16/1994), 79.18% (1579/1267) of applications; and “deferred” 20.81% (415/1994) of applications. AI and DDT were 99.37% (1553/1563) concordant to authorize and 100% (16/16) concordant to reject a beneficiary application. DDT spent an average of 3.4 minutes/deferred application. Conclusions: A clinically validated AI system, 99% concordant with cancer experts in authorizing or rejecting 79% of beneficiary applications, promises a fivefold decrease in experts’ time, the scarcest resource for preauthorization. Subsequent to this study, ICS-CCF is awarding financial support directly based on AI authorize decisions. Similarly, health insurance organizations may consider a prospective study of the AI system in raising quality and efficiency of prior authorization thereby saving cost of time, money and expertise.
Citation Format: Tushar Vora, Nehal Khanna, Anant Gokarn, Ann Rawat, Naresh Ramarajan, Gitika Srivastava, Usha Thorat. Enhancing impact and efficiency of financial support for cancer through use of AI: A nascent initiative of Indian cancer society [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-16-02.
Abstract P3-18-02: Breast conservation plus radiotherapy provides superior survival benefit than mastectomy in triple negative breast cancer: A propensity matched national cancer database analysis
Authors: Cao Lifen , Towe Christopher W , Miller Megan E , Montero Alberto J , Shenk Robert 
Published: March 2022

Abstract
Background: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with a higher risk of locoregional and distance recurrence. Consequently, this population was considered poor candidate for breast conservation (BCT). Our study aim was to determine whether BCT plus radiotherapy (RT) was equivalent to mastectomy for TNBC after adjustment of selection bias of demographic and clinical characteristics. Methods: The National Cancer Database was queried for women diagnosed as primary unilateral invasive clinical T1-2N0-2 TNBC from 2004-2016. Patients who underwent mastectomy or breast conservation (partial mastectomy plus radiation) were included. A 1:1 propensity match with replacement was performed to compare breast conservation vs. mastectomy. Overall survival was analyzed using stratified multivariable Cox proportional hazard regression analysis.Results: Of 59,599 clinical T1-2N0-2 TNBC patients, 26,325 (44.2%) underwent mastectomy and 33,274 (55.8%) were treated with BCT. BCT patients were older (median age 59 vs. 54, p&lt;0.001), had smaller tumors (cT1 61.7% vs. 42.9%, p&lt;0.001) and node negative (cN0 85.8% vs. 73.7%, p&lt;0.001). Propensity matching reduced the bias between mastectomy and breast conservation groups and generated 30,980 pairs for analysis. Median follow-up times were 41 months (range 6.97-95.8) and 39 months (range, 0.62 -94.06) for BCT and mastectomy groups, respectively. After matching, BCT+RT was associated with significantly higher OS compared to mastectomy ( 86.8% vs. 79.7%, p&lt;0.001). The survival advantage was also present in multivariate cox regression after controlling age, race, insurance, facility type, clinical T and clinical N stage.Conclusions: Using both propensity matching and multivariate cox regression controlling for potential confounders, BCT+RT survival was superior to mastectomy in a retrospective analysis of a large cancer database.
Citation Format: Lifen Cao, Christopher W Towe, Megan E Miller, Alberto J Montero, Robert Shenk. Breast conservation plus radiotherapy provides superior survival benefit than mastectomy in triple negative breast cancer: A propensity matched national cancer database analysis [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-18-02.
Abstract P3-19-05: Genomic machine learning model predicts radiation therapy benefit in early-stage breast cancer patients with high accuracy
Authors: Badal Kimberly , Foster Jerome , Haraksingh Rajini , John Melford 
Published: March 2022

Abstract
Background: Radiation therapy (RT) is frequently recommended for post-surgery treatment of early-stage breast cancer (BC) patients, though not all benefit. Clinical factors currently guide RT treatment decisions. This work presents a high-accuracy genomic machine learning (ML) model to predict RT-benefit in early-stage BC patients and a novel method for selecting genomic features for ML algorithms. Methods: Gene expression data from 477 early-stage BC patients treated with surgery and RT from the METABRIC cohort were obtained. Wilcoxon Rank Sum (Wilcox RS) test and Cox Proportional Hazards (Cox PH) were used to reduce the number of genes used to train 8 ML algorithms. Each ML algorithm was trained on a random subset of 80% of the data using 10-fold cross-validation and tested on the remaining 20% to assess its performance in predicting relapse status within 30 years. Results: The genomic data were reduced using Wilcox RS and Cox PH to a 1,596 gene set and a 977 gene set. These gene sets when used to train the 8 ML algorithms resulted in models that ranged in performance accuracies from 54.01% to 95.6%. The highest accuracies were obtained using Support Vector Machine (SVM977 - 93.41%, SVM1596 - 95.6%) and Neural Networks (NN977 - 92.31%, NN1596 - 93.41%). The accuracy of all models when tested on RT-untreated patients was 30-40% lower compared to RT-treated patients. SVM977 had the highest sensitivity of 91.09%. Members of the 977 gene set were enriched with genes involved in the cell cycle and differentiation as well as radiogenes. Conclusion: We developed an SVM model that used 977 differentially expressed genes as features that predicted RT-benefit in early-stage BC patients with 93.41% accuracy and 91.09% sensitivity. We also developed a novel genomic feature selection approach that used Wilcoxon RS followed by Cox PH that resulted in expression values of only 4% of all genes being used as features in the models.
Citation Format: Kimberly Badal, Jerome Foster, Rajini Haraksingh, Melford John. Genomic machine learning model predicts radiation therapy benefit in early-stage breast cancer patients with high accuracy [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-05.
Abstract P3-20-08: Does contralateral prophylactic mastectomy improve survival in triple negative breast cancer?
Authors: Fasano Genevieve A , Bayard Solange , Chen Yalei , Marti Jennifer , Simmons Rache , Swistel Alexander , Bensenhaver Jessica , Nathanson S David , Petersen Lindsay , Proctor Erica , Davis Melissa , Newman Lisa 
Published: March 2022

Abstract
Background: Despite increased incidence of contralateral prophylactic mastectomy (CPM), there is insufficient evidence that it improves survival in women at average risk for breast cancer. In addition to BRCA1/2 mutation carriers, patients with estrogen-receptor negative tumors have been examined as a subgroup that may seek to benefit from CPM. In this study, we sought to investigate whether CPM improves survival in patients with triple negative breast cancer (TNBC).Study Design: Survival outcomes were evaluated for all TNBC patients from a multi-institutional database from 1999-2018 at New York Presbyterian - Weill Cornell Medical Center and Henry Ford Health System. Median follow-up time was 44.4 months.Results: 802 TNBC patients were evaluated. The median age was 57 years. 17% patients underwent CPM. Factors associated with CPM were White American race, younger age, presence of lymphovascular invasion (LVI), lack of mammography screen-detection, mastectomy surgery, postoperative adjuvant radiotherapy, and having had genetic testing. A borderline significant trend was observed in improved overall survival among patients undergoing CPM versus those not having CPM (5-year OS 95.1% vs. 85.0%; p = 0.05). Subset analysis of patients younger than 50 years of age at diagnosis demonstrated no improvement in overall survival for patients undergoing CPM versus those that declined CPM (94.3% v. 88.7%; p = 0.21). Conclusion: Our data demonstrate a trend in improved 5-year overall survival in TNBC patients undergoing CPM. However, in patients younger than 50 years at diagnosis, CPM did not confer a survival advantage.
Citation Format: Genevieve A Fasano, Solange Bayard, Yalei Chen, Jennifer Marti, Rache Simmons, Alexander Swistel, Jessica Bensenhaver, S David Nathanson, Lindsay Petersen, Erica Proctor, Melissa Davis, Lisa Newman. Does contralateral prophylactic mastectomy improve survival in triple negative breast cancer? [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-20-08.