bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P5-07-14: Chronic kidney disease in breast cancer treatment and survival
Authors: Hill Deirdre A , Argyropoulos Christos , Roumelioti Maria-Eleni , Unruh Mark 
Published: March 2020

Abstract
Background: Presence of chronic kidney disease (CKD Stages 3-5) prior to breast cancer diagnosis may increase the risk of mortality among women with invasive breast cancer. However, the evidence base is limited, and the magnitude of this mortality risk is unknown. Breast cancer therapy may also be altered by presence of CKD. We sought to understand the role of CKD in breast cancer survival, with particular attention to receipt of recommended treatment.
Methods: All women diagnosed with invasive breast cancer from 1992-2016 in 18 SEER-Medicare sites (age 66 or older; n= 168701) were evaluated for breast cancer-specific mortality (BCSM) using multivariate Cox models, with estimation of hazard ratios (HR) and 95% confidence intervals (CI). All analyses were adjusted for age, race/ethnicity, diagnosis year, tumor characteristics, and socioeconomic factors, and also for diabetes, myocardial infarction, and congestive heart failure prior to diagnosis. Separate analyses were run according to receipt vs non-receipt of standard of care for breast cancer treatment (defined according to National Comprehensive Cancer Network (NCCN) guidelines.
Results: Median follow-up was 63 months (26 months with CKD). Women with CKD were at increased risk of BCSM (CKD Stage 3: HR 1.2; 95% CI 1.0-1.5; CKD Stage 4 HR 1.7; 95% CI 1.3-2.2; CKD Stage 5/End Stage Renal Disease HR 1.5; 95% CI 1.1-2.1), compared to women without CKD. In analyses of any CKD, restricted to women who met NCCN guideline therapy recommendations, women had an elevated risk of BCSM regardless of whether they did (HR 1.6; 95% CI 1.1-2.1) or did not (HR 1.4; 95% CI 1.0-1.8) receive recommended chemotherapy, and whether they did (HR 1.6; 95% CI 1.1-2.3) or did not (HR 1.3; 95% CI 0.9-2.0) receive recommended radiotherapy.
Discussion: Women with CKD have an increased risk of breast cancer mortality regardless of receipt of guideline-based treatment. CKD is underascertained in Medicare claims data, thus the reported results (likely underestimates) will be presented with sensitivity analyses. CKD may influence breast cancer outcomes due to associated systemic inflammation and comorbid conditions, as well as release of soluble mediators such as cytokines, chemokines, growth factors, and factors involved in remodeling of the extracellular matrix and epithelial-mesenchymal transition. As such factors involved in CKD progression also influence cancer, increased understanding may provide clues to ameliorate adverse outcomes in both disease entities.
Citation Format: Deirdre A Hill, Christos Argyropoulos, Maria-Eleni Roumelioti, Mark Unruh. Chronic kidney disease in breast cancer treatment and survival [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-07-14.
Abstract P5-08-19: The risk of breast, ovarian and endometrial cancer in obese women submitted to bariatric surgery: A meta-analysis
Authors: Ishihara Beatriz Pércia , Farah Daniela , Fonseca Marcelo Cunio Machado , Nazário Afonso Celso Pinto 
Published: March 2020

Abstract
Background: Obesity is related to major risk factors for a number of noncommunicable diseases including cancer. There is a high incidence of breast and endometrial cancer in obese women. Thus, we performed a systematic review followed by meta-analysis to evaluate the relationship between bariatric surgery, a method widely used to treat obesity, and the risk of developing breast, ovarian and endometrial cancer in obese women.
Methods: MEDLINE, EMBASE, LILACS and Cochrane databases were searched from inception until January 2019 which retrieve studies to assessed the risk of breast, ovarian and endometrial cancer in obese women submitted to bariatric surgery. There was no language restriction. We extracted and combined data from studies in order to assess the risk ratio (RR) of developing these cancers. A random-effects, meta-analytic model was applied in all calculations. The New Castle Ottawa and GRADE were used to assess quality and bias of the included studies. Trial registered in PROSPERO (CRD42019112927).
Results: We found 188 articles and only seven of those were included in our meta-analysis, which incorporated a total of 150,528 patients in the bariatric surgery arm and 1,461,938 women in the control arm. The total risk of developing breast, ovarian and endometrial cancer was 0.37 (95%CI [0.28 to 0.48]; I2=87%; 7 studies). The risk of breast cancer was reduced by 61% [RR: 0.39 (95%CI [0.24 to 0.64]; I2= 90%; 6 studies). The risk of ovarian cancer was reduced by 53% [RR: 0.47 (95%CI [0.27 to 0.81]; I2= 0%; 3 studies). The risk of endometrial cancer was reduced by 67% [RR: 0.33 (95%CI [0.21 to 0.51]; I2= 88%; 7 studies).
Conclusion: Bariatric surgery may have a protective effect by reducing the risk of developing breast, ovarian and endometrial cancer in obese women. However, high heterogeneity was found and not explained by our subgroup analysis. Although we couldn’t separate the types of surgeries performed, we hypothesized that the high heterogeneity might be due to the types of surgery. Therefore, we suggest more research with appropriate report of the type of the surgery by group.
Citation Format: Beatriz Pércia Ishihara, Daniela Farah, Marcelo Cunio Machado Fonseca, Afonso Celso Pinto Nazário. The risk of breast, ovarian and endometrial cancer in obese women submitted to bariatric surgery: A meta-analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-08-19.
Abstract P6-03-18: The accumulation of IGFBP-1 results in EGFR/MAPK activation and drives the development of tamoxifen resistance in breast cancer cells
Authors: Zheng Yan 
Published: March 2020

Abstract
Insulin-like growth factor (IGF) system plays a significantly role in cellular processes, including proliferation, survival, and mitogenesis. The IGF system consists of two soluble ligands, IGF-1 and IGF-2; two transmembrane receptors, IGF-1R and IGF-2R; and six high affinity IGF binding proteins, IGFBPs 1-6. Evidence shows that the IGF system is involved in breast cancer. For example, at least 50% of breast cancer tumors have elevated IGF-1R signaling; the level of circulating IGF-1 is found positively associated with the incident of estrogen receptor positive breast cancer. Tamoxifen, a selective estrogen receptor modulator and antagonist for estrogen receptor alpha (ERα) in breast tissue, is a commonly prescribed adjuvant treatment for patients presenting with ERα-positive breast cancer. However, tamoxifen resistance also occurs, and its exact mechanism is not well understood. Recently, we discovered that the accumulation of IGFBP-1 was stimulated by tamoxifen treatment, which subsequently prevented the activation of IGF-1R and inhibited the proliferation in MCF-7 cells. As a result, we hypothesized that the accumulation of IGFBP-1 due to the long-term tamoxifen exposure would result in tamoxifen resistance. In order to mimic the accumulation of IGFBP-1 after tamoxifen treatment, we employed MCF-7 and T-47D breast cancer cells to generate stable cell lines with IGFBP-1 overexpression. We found that the expression of IGF-1R was largely reduced in both MCF7-BP1 and T47D-BP1 cells, which was also observed in tamoxifen resistant MCF-7 and T-47D cells. Furthermore, we demonstrated that both MCF7-BP1 and T47D-BP1 were not responsive to tamoxifen, and epidermal growth factor receptor (EGFR) signaling pathway was significantly upregulated, as shown by higher levels of EGFR, phospho-EGFR (pEGFR), and phospho-Erk (pErk). Also, we found that the inhibition of Erk phosphorylation by MEK1 inhibitor PD98059 sensitized the stable cells to tamoxifen, showing that elevated pErk was protective against tamoxifen. Lastly, the transient knockdown of IGFBP-1 in MCF7-BP1 and T47D-BP1 resulted in significantly lower level of pErk and increased sensitivity to tamoxifen, further showing the role of IGFBP1 accumulation in the establishment of tamoxifen resistance and the activation of EGFR/MAPK pathway.
Citation Format: Yan Zheng. The accumulation of IGFBP-1 results in EGFR/MAPK activation and drives the development of tamoxifen resistance in breast cancer cells [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-03-18.
Abstract P6-06-15: Remodelling of calcium influx pathways in breast cancer associated fibroblasts
Authors: Sadras Francisco , Stewart Teneale A , Robitaille Melanie , Peters Amelia A , Kalita-de Croft Priyakshi , Soon Patsy , Saunus Jodi M , Lakhani Sunil R , Roberts-Thomson Sarah J , Monteith Gregory R 
Published: March 2020

Abstract
Disruption of Ca2+ signaling during breast cancer tumorigenesis is now well-established. Despite the increasing recognition of the role of the tumour microenvironment, and cancer associated fibroblasts (CAFs), in tumorigenesis, very few studies have assessed alterations in Ca2+ influx pathways in this context. The aims of this study were to identify changes in the nature of Ca2+ influx in breast CAFs and to define the role of Ca2+ signaling in the induction of CAFs.
We first developed a model for CAF induction using an immortalized human mammary fibroblast cell line, HMF3S. These cells were treated with transforming growth factor beta (TGFβ) to induce a CAF phenotype (HMF3S-CAF) as confirmed by the induction established CAF markers, including alpha smooth muscle actin. Fluorescence Imaging Plate Reader Ca2+ assays demonstrated that store operated Ca2+ entry (SOCE) was reduced as a consequence of TGFβ stimulated CAF induction in HMF3S-CAFs. As a potential mechanism, mRNA levels of the SOCE components, ORAI1, STIM1 and STIM2 were assessed. STIM2 was downregulated and ORAI1 was slightly upregulated suggesting that the decrease in SOCE in HMF3S-CAF cells were independent of mRNA expression changes of these genes.
Voltage gated calcium channel (VGCC) mRNA expression was measured to determine whether other Ca2+ influx pathways were altered during CAF differentiation. Here, we found that Cav 1.2 and Cav 3.2 were significantly upregulated in HMF3S-CAF cells. Assessment of mRNA levels of SOCE components and VGCC in paired normal and CAF patient samples showed no change in SOCE components while, of the VGCCs, only Cav 1.2 and Cav 3.2 were upregulated, suggesting that increased expression of these channels may be a feature of breast cancer CAFs.
The importance of Cav 1.2 and Cav 3.2 in CAF induction was assessed by pharmacological inhibition using nimodipine (Cav 1.2) or ML218 (Cav 3.2), both of which decreased TGFβ-mediated CAF activation. Our preliminary data suggest that siRNA against specific VGCCs may also reduce CAF activation. Our data indicate that Ca2+ signaling is remodelled in CAFs and that VGCC Ca2+ signal is important for breast CAF induction.
Citation Format: Francisco Sadras, Teneale A Stewart, Melanie Robitaille, Amelia A Peters, Priyakshi Kalita-de Croft, Patsy Soon, Jodi M Saunus, Sunil R Lakhani, Sarah J Roberts-Thomson, Gregory R Monteith. Remodelling of calcium influx pathways in breast cancer associated fibroblasts [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-06-15.
Abstract P6-10-28: Therapeutic stratification of triple negative breast cancer by integrating chemosensitivity & phospho-proteome profiles
Authors: Gautam Prson , Qin Xiangju , Vainonen Julia , Nagelli Srikar , Lampe Johanna , Klefström Juha , Westermarck Jukka , Wennerberg Krister , Aittokallio Tero 
Published: March 2020

Abstract
Triple negative breast cancer (TNBC) is a highly aggressive type of breast cancer with poor prognosis that accounts approximately for 15% of breast cancer cases. The lack of targetable hormonal receptors or HER2/ErbB2 makes TNBC therapeutically challenging and existing drug treatments are often ineffective. TNBC is also a highly heterogeneous class of breast cancer, and different genetic approaches have not been so far successful in identifying clinically useful patient stratification strategies to date. In previous studies, we have discovered a correlation between targeted phospho-proteomics and mitotic inhibitor sensitivities in TNBC cells, suggesting the potential of using phospho-proteome profiles to identifying markers predictive of actionable therapeutic strategies. In the current study, we further explored the potential of phospho-proteomics for TNBC stratification and drug chemo-sensitivity prediction. We screened 25 TNBC cell lines against 517 oncology compounds, and in parallel ran mass spectrometry-based global phospho-proteome profiling of the same cell lines, resulting in 4283 confident phospho-peptide quantifications. Using multitask multiple kernel learning, we integrated the phospho-peptide data with other publicly available omics data for the 25 TNBC cell lines (genomics, transcriptomics, metabolomics, and methylomics), and developed a multi-omics machine learning model to quantify the predictive contribution of each omics profile to drug response prediction. When considering all the 517 compounds, we found that the phospho-proteomic and gene expression data were most informative for the prediction of compound’s chemo-sensitivity. This integrated approach has the potential to both identify panels of multi-omics markers for individual drug classes, as well as to stratify the heterogeneous TNBC cells based on their genomic, molecular and functional profiles.
Citation Format: Prson Gautam, Xiangju Qin, Julia Vainonen, Srikar Nagelli, Johanna Lampe, Juha Klefström, Jukka Westermarck, Krister Wennerberg, Tero Aittokallio. Therapeutic stratification of triple negative breast cancer by integrating chemosensitivity & phospho-proteome profiles [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-10-28.
Abstract A1: Clinical outcomes in patients with chronic hepatitis C and metastatic renal cell carcinoma (mRCC) after treatment with nivolumab
Authors: Tsimafeyeu Ilya , Gafanov Rustem , Semenova Anna , Oganesyan Ani , Bondarenko Anastasia , Safina Sufia , Zakurdaeva Kristina , Protsenko Svetlana 
Published: March 2020

Abstract
Clinical trials of immune checkpoint inhibitors have historically excluded patients with chronic hepatitis C (HCV) infection. The safety and efficacy profile of nivolumab is unknown in this under-represented population. Data were collected in a retrospective fashion on 36 patients with metastatic clear-cell mRCC. Patients were required to have a chronic HCV infection, no evidence of other malignancy or cirrhosis, and to have received nivolumab (3 mg/kg every 2 weeks) as second- or third-line therapy. Clinical outcomes included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Safety was evaluated. Median follow-up was 17.5 months. Nivolumab was well tolerated in all HCV-infected patients (grade 3-4 toxicity was found in 6 of 36 cases [17%]). No unexpected toxicity was observed. Exposure to nivolumab was not associated with increased risk for hepatocellular carcinoma and cirrhosis (N=0). Medians OS and PFS were 23.9 (95% CI 20.7-26.5) and 6.8 (95% CI 4.9-8.7) months, respectively. 23% of patients had partial responses. The efficacy and safety profile observed in this study supports the administration of nivolumab in mRCC patients infected with HCV and warrants further investigation.
Citation Format: Ilya Tsimafeyeu, Rustem Gafanov, Anna Semenova, Ani Oganesyan, Anastasia Bondarenko, Sufia Safina, Kristina Zakurdaeva, Svetlana Protsenko. Clinical outcomes in patients with chronic hepatitis C and metastatic renal cell carcinoma (mRCC) after treatment with nivolumab [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr A1.
Abstract A20: Cancer cell-intrinsic expression of MHCII regulates the immune microenvironment and response to immune therapy in lung adenocarcinoma
Authors: Johnson Amber M. , Bulock Bonnie L. , Neuwelt Alexander J. , Schenk Erin L. , Clambey Eric T. , Nemenoff Raphael A. 
Published: March 2020

Abstract
Immune checkpoint inhibitors targeting PD-1/PD-L1 interactions have shown clinical efficacy in the treatment of multiple cancer, including non-small cell lung cancer (NSCLC). However, the factors determining the extent and duration of therapy are incompletely understood. While antigen presentation via MHC class I interacting with CD8+ T cells has been characterized, the role of MHC class II (MHCII) interacting with CD4+ T cells is less well defined. MHCII expression is usually restricted to antigen-presenting cells, but can be expressed by cancer cells. We examined the effect of cancer cell-intrinsic MHC class II (csMHCII) expression in lung adenocarcinoma on T-cell recruitment to tumors and response to anti-PD-1 therapy. The functional significance of altering csMHCII expression was explored using two orthotopic immunocompetent murine models of non-small cell lung cancer: CMT167 (CMT) and Lewis Lung Carcinoma (LLC). We previously showed that CMT167 tumors are eradicated by anti-PD1 therapy, while LLC tumors are resistant. RNA-seq analysis of cancer cells recovered from tumors revealed that csMHCII correlated with response to anti-PD1 therapy, with immunotherapy-sensitive CMT167 cells being csMHCII positive, while resistant LLC cells were csMHCII negative. To test the functional effects of csMHCII, MHCII expression was altered on the cancer cells through loss and gain of function of CIITA, a master regulator of the MHCII pathway. Loss of CIITA in CMT167 decreased csMHCII and converted tumors from immunotherapy sensitive to immunotherapy resistant. This was associated with decreased T-cell infiltration and lower levels of Th1 cytokines. Conversely, overexpression of CIITA in LLC cells resulted in csMHCII in vitro and in vivo. Enforced expression of CIITA increased T-cell infiltration and sensitized tumors to anti-PD-1 therapy. csMHCII expression was also examined in a subset of surgically resected human lung adenocarcinomas by multispectral imaging, and positively correlated with T-cell infiltration. These studies demonstrate a functional role for csMHCII in regulating T-cell infiltration and sensitivity to anti-PD-1.
Citation Format: Amber M. Johnson, Bonnie L. Bulock, Alexander J. Neuwelt, Erin L. Schenk, Eric T. Clambey, Raphael A. Nemenoff. Cancer cell-intrinsic expression of MHCII regulates the immune microenvironment and response to immune therapy in lung adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr A20.
Abstract A28: A comparison of a DNA-sourced neoantigen vaccine to an RNA-sourced frameshift vaccine in the mouse ovarian cancer model
Authors: Batista Milene Tavares , Murphy Sierra , Lainson John , Shen Lui , Johnston Stephen 
Published: March 2020

Abstract
Development of cancer vaccines is currently focused on using neoantigens arising from mutations in the DNA of tumors. We have proposed, and demonstrated, that errors in RNA processing that create frameshift (FS) neoantigens are also a good source of vaccine components, even in tumors that are DNA mutation poor. Here we directly compare the two vaccine approaches in the mouse ovarian model, ID8. Martin et al. (2016) reported that 7 DNA neoepitopes in the ovarian tumor line (ID8-G7) failed to show any protection when tested individually as peptide vaccines even though the peptides elicited an immune response. We created a pooled peptide vaccine consisting of these 7 neoantigens (NeoAg vax). We compared this vaccine to one composed of 13 RNA-sourced FS neoantigens (FS vax). These FSs had conferred protection when tested in the 4T1 mammary and/or B16 melanoma models. 10 of the FSs arise from mis-transcription thru microsatellites and 3 from mis-splicing of exons. In a prophylactic vaccination protocol, both vaccines induce ~20% extended survival compared to mock controls. The FS vax elicited higher numbers of ELISpots than the ID8 control while the NeoAg vax did not when splenocytes were peptide stimulated. The FS vax and NeoAg vax induced T-cells were only significantly cytotoxic to the ID8 cells if anti-PD-L1/CTLA-4 antibodies were included. In the therapeutic vaccination protocol, both the FS vax and the NeoAg vax conferred extended survival in ~20% of the mice compared to controls. Neither vaccine induced more ELISpots compared to controls using peptides. However, the FS vax did elicit more ELISpots in response to ID8 stimulation and more ID8 cytotoxicity than the NeoAg vax. From this work we first conclude that the DNA-sourced neoantigens that did not protect individually can when pooled. Secondly, and more importantly, the RNA-sourced, FS neoantigens can perform as well as the DNA-sourced neoantigens, at least in this model. This may be important as we have shown that all tumors surveyed to date, in contrast to DNA neoantigens, have abundant RNA-sourced FS neoantigens.
Citation Format: Milene Tavares Batista, Sierra Murphy, John Lainson, Lui Shen, Stephen Johnston. A comparison of a DNA-sourced neoantigen vaccine to an RNA-sourced frameshift vaccine in the mouse ovarian cancer model [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr A28.