bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-19-07: Real-world characteristics, treatment patterns, and overall survival in patients with metastatic breast cancer (mBC) and CNS metastases
Authors: Alvarado-Miranda A , Cabrera-Galeana P , Muñoz-Montaño WR , Lara-Medina F , Bargallo-Rocha E , Arrieta-Rodriguez O , Perez M , Porras-Reyes F , Mohar-Betancourt A , Gamboa C 
Published: May 2019

Abstract
Background:
CNS metastases are reported in about 10 to 15%. Knowledge about the management of these patients are limited because they are excluded from clinical trials due to its poor prognosis and morbidity. In these study, we aim to describe characteristics, treatment patterns, and overall survival (OS) of patients of mBC with CNS metastases at Instituto Nacional de Cancerología de Mexico (INCan) from january 2007 to december 2015.
Methods:
We include patients with histological diagnosis of mBC and tumoral activity in the CNS (at diagnosis or during de follow-up). mBC subtype was defined using HER2 and hormone receptor (HR) status by immunohistochemistry; systemic treatment, and mortality data were used to characterize mBC with CNS involment.
Results:
During the study period, we found 1272 patients diagnosed with metastatic disease, of whom 408 had CNS disease (novo/recurrence) the median follow up was 52 months. Table 1 describes the percentage of CNS metastases by subtype, clinical characteristics at diagnosis and median OS. Almost all patients (85.6%) were candidate to holocranial radiotherapy; after that, systemic treatment varied according to the subtype of mBC; 69.1% of TN received CT (26% based on platinum); 75.3% of HER2+ received systemic treatment, all included antiher2 therapy; luminal subtype, no one were treated with endocrine therapy.
Table 1.- characteristics and Overall suvival by subtype of mBC all mBC 1272 n(%)her2 positive 339 (26.6) n (%)triple negative 298 (23.4) n(%)luminal 636 (50) n(%)CNS metastasis at dianosis44 (3.5)12 (3.5)13 (4.4)19 (2.9)CNS mets after prog to systemic tx205(16.1)63(18.6)50(16.7)92(14.5)CNS as first place of recurrence159(12.5)75(22.2)34(11.4)50(7.8)prevalence on CNS mets408(10.7)150(14.7)97(10.8)161(8.4)median age at diagnosis of CNS mets50(28-84)50(29-84)48(28-80)51(28-80)median OS after CNS mets (months)14.927.29.3316.3
Conclusions:
HER2 positive breast cancer patients have the highest prevalence of CNS metastases, whereas luminal has the lowest. Patients with HER2+ and CNS metastases commonly receive treatment based on anti-HER2 therapy, maybe this target treatment contribute to the better survival achieved than patients with luminal or TN subtype. mBC with CNS metastases continues in the real world to be an unmet medical need.
Citation Format: Alvarado-Miranda A, Cabrera-Galeana P, Muñoz-Montaño WR, Lara-Medina F, Bargallo-Rocha E, Arrieta-Rodriguez O, Perez M, Porras-Reyes F, Mohar-Betancourt A, Gamboa C. Real-world characteristics, treatment patterns, and overall survival in patients with metastatic breast cancer (mBC) and CNS metastases [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-19-07.
Abstract P2-01-15: Inflammatory breast cancer cells are characterized by attenuated SMAD dependent TGFβ signaling leading to impaired cell motility responses
Authors: Rypens C , Van Berckelaer C , Billet C , Hauspy J , Bertucci F , Peter V , Dirix L , Van Laere S 
Published: May 2019

Abstract
Introduction.Inflammatory breast cancer (IBC) is an aggressive form of locally advanced breast cancer with elevated metastatic potential, characterized by the frequent presence of tumor emboli in dermal and parenchymal lymph vessels. In the past, evidence was provided that TGFβ signaling is part of the molecular biology of this disease. In this study, this relation was further examined.
Materials and methods. TGFβ1 induced cell motility (i.e. XCELLigence, wound healing assays), gene expression (RNA-sequencing) and peptide phosphorylation (i.e. PAMGene technology) patterns were investigated in a panel of 3 IBC and 3 subtype-matched nIBC cell lines. In addition, a series of tissue samples from 75 and 135patients with and without IBC was investigated for nuclear expression of total SMAD2, SMAD3 and SMAD4 using immunohistochemistry. Finally, SMAD protein expression data were related to gene expression data from patients with available Affymetrix HGU133plus2 profiles.
Results. The cell motility inducing capacity of TGFβ1 was strongly abrogated in all IBC cells independent of their molecular subtype (P=0.003). Genes differentially expressed between IBC and nIBC cells post 4 hours of TGFβ1 revealed attenuated expression of SMAD3 transcriptional regulators with concomitant overexpression of MYC target genes in IBC. Assessment of SMAD expression in patient samples demonstrated a near absence of nuclear SMAD3 expression in the primary tumors from patients with IBC (P&lt;0.001) and a further reduction of SMAD3 staining intensity was observed in tumor emboli (P=0.019). Integrated analysis of gene and protein expression data revealed that a substantial fraction of the IBC signature genes correlated with SMAD3 and these genes (i.e. 21/24; P&lt;0.001) carry evidence in favor of attenuated SMAD3 signaling in IBC.
Discussion. It is demonstrated that IBC cells are characterized by attenuated SMAD3 protein expression and transcriptional activity that obliterates the cell motility inducing capacity of TGFβ1. Recent studies revealed that SMAD3 is essential for TGFβ1 induced cell motility through induction of epithelial to mesenchymal transition (EMT). In the absence of SMAD3 expression, a partial EMT is induced leading to collectively invading cancer cells that are gifted with a high metastatic potential and favor lymphatic dissemination, thereby providing an intriguing explanatory model of the biology of tumor emboli in IBC.
Citation Format: Rypens C, Van Berckelaer C, Billet C, Hauspy J, Bertucci F, Peter V, Dirix L, Van Laere S. Inflammatory breast cancer cells are characterized by attenuated SMAD dependent TGFβ signaling leading to impaired cell motility responses [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-01-15.
Abstract P2-01-17: Not presented
Authors: Dravis CP , Chung C-Y , Wahl GM 
Published: May 2019

Abstract
This abstract was not presented at the conference.
Citation Format: Dravis CP, Chung C-Y, Wahl GM. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-01-17.
Abstract P2-01-25: Not presented
Authors: Xing W , Li Q , Cao R , Sun G , Jiang C 
Published: May 2019

Abstract
This abstract was not presented at the conference.
Citation Format: Xing W, Li Q, Cao R, Sun G, Jiang C. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-01-25.
Abstract P2-02-14: Metabolic regulation and drug resistance in c-Src activated triple negative breast cancer
Authors: Jung KH , Park JH , Sirupangi T , Jia D , Gandhi N , Pudakalakatti S , Elswood J , Porter W , Putluri N , Zhang XH-F , Chen X , Bhattacharya PK , Creighton CJ , Lewis MT , Rosen JM , Wong L-JC , Das GM , Osborne CK , Rimawi MF , Kaipparettu BA 
Published: May 2019

Abstract
c-Src (Src) is a proto-oncogene involved in signaling that culminates in the control of multiple biological functions. Src is also one of the most frequently upregulated pathways in triple negative breast cancer (TNBC). Dysregulation of Src has been detected in TNBC and is strongly associated with tumor metastasis and poor prognosis. However, even after promising preclinical studies, Src inhibitors did not show major clinical advantage in unselected TNBC populations. We have previously published that metastatic TNBC has high energy-dependency to mitochondrial fatty acid beta-oxidation (FAO) and FAO activates Src by inducing autophosphorylation at Y419. However, our recent analysis suggests that as observed with the Src inhibitors, TNBC tumors treated with FAO inhibitors also develop drug-resistance and continue tumor growth. Evaluation of their drug resistance mechanism revealed that while short-term inhibition of FAO or Src induces autophagic and apoptotic cell deaths, long-term inhibition results in autophagy-mediated drug resistance and survival. Further analyses suggest that FAO and Src inhibitors activate mitogen-activated protein (MAP) kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway via the induction of cellular reactive oxygen species (ROS) in TNBC. Activated MEK/ERK then induces survival pathways for drug resistance and tumor survival. Validation of in vitro findings using in vivo TNBC models confirmed that combination of FAO/Src inhibitors with MEK/ERK inhibitors can provide significant benefit to overcome the therapeutic resistance of TNBC. These findings open-up new therapeutic opportunities to manage TNBC patients with currently non-targetable metastatic tumors.
Citation Format: Jung KH, Park JH, Sirupangi T, Jia D, Gandhi N, Pudakalakatti S, Elswood J, Porter W, Putluri N, Zhang XH-F, Chen X, Bhattacharya PK, Creighton CJ, Lewis MT, Rosen JM, Wong L-JC, Das GM, Osborne CK, Rimawi MF, Kaipparettu BA. Metabolic regulation and drug resistance in c-Src activated triple negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-02-14.
Abstract P2-03-05: S100A7 enhances triple negative breast cancer growth and metastasis by cross-talk with resistin
Authors: Mishra S , Ahiwar DK , Shukla RK , Chatterjee N , Ganju R 
Published: May 2019

Abstract
Triple negative breast cancer (TNBC) represents ˜20% of all breast cancer cases and is highly refractory to existing therapies. Although, a number of putative functions have been proposed for S100A7, but its crosstalk with resistin in TNBC pathogenesis remains to be defined. S100A7/RAGE signaling has been shown to play an important role in inflammation-mediated breast cancer pathogenesis. S100A7/psoriasin, a member of the epidermal differentiation complex, is widely overexpressed in invasive estrogen receptor (ER)α-negative breast cancers. Thus, the objective of this study is to explore the cross-talk between S100A7 and resistin in TNBC cells. In this study, we observed that the treatment or overexpression of S100A7 increased the expression of resistin, cPLA2 and FASN expressions in TNBC cells. The overexpression/downregulation of S100A7 with exogenous resistin in TNBC cells also showed the marked changes in their migrating, sphere forming and colony forming abilities. The treatment of resistin also increases the effect of S100A7-mediated expansion of breast cancer stem cells (BCSCs) by increasing the ALDH activity and CD44+CD24- subpopulations. The in-vivo effects of resistin on breast tumor growth and metastasis were also analyzed by using MDA-MB-231 vector and S100A7 overexpressed MDA-MB-468 vector and S100A7 knock-down cells by using Xenograft NOD/SCID Il2rg null (NSG) mice model. Here, we have found that the treatment of resistin increased the tumor growth and metastases mediated by S100A7 by modulating the different myeloid cells populations. We have also shown that the S100A7 overexpressed MDA-MB-231 cells were much more sensitive to FASN and cPLA2 inhibitors as compared to vector control cells. The in-silico analyses also showed the clinical significance of S100A7 and resistin in TNBC pathogenesis. Collectively, these findings suggest the novel cross-talk in between S100A7 and resistin in TNBC pathogenesis and how resistin, cPLA2 and FASN could be used as potential therapeutic targets to inhibit the S100A7-mediated TNBC progression and metastasis.
Citation Format: Mishra S, Ahiwar DK, Shukla RK, Chatterjee N, Ganju R. S100A7 enhances triple negative breast cancer growth and metastasis by cross-talk with resistin [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-03-05.
Abstract P2-03-12: Role of nucleus-specific intergenic long noncoding RNA-1476 in estrogen-dependent transcription in cancer
Authors: Choudhari R , Harrison AL , Carrillo CN , Gadad SS 
Published: May 2019

Abstract
Long noncoding RNAs (lncRNAs) are emerging as key regulators of diverse cellular processes, but their roles in cancer biology are just beginning to be elucidated. Previous work using Global Run-On sequencing (GRO-seq) to study the transcriptome of MCF-7 breast cancer cells identified a large number of unannotated noncoding RNAs. Integration of RNA-seq data from subcellular fractionated RNA (i.e., cytoplasm, nucleoplasm, and chromatin-associated) with GRO-seq data using a novel bioinformatics pipeline has yielded a comprehensive catalog of &gt;1900 polyadenylated lncRNAs in MCF-7 cells, about half of which have not been annotated previously and about a quarter of which are estrogen-regulated. Analysis of RNA-seq data from hundreds of samples representing 13 different cancer and normal tissue types, revealed that many lncRNAs are differentially expressed in various cancers. Furthermore, a large number of lncRNAs show distinct expression patterns across molecular subtypes of cancer. In functional assays, Kaplan Meier analysis of selected lncRNA, such as lncRNA 1476, predicts clinical outcome in ER-positive cancer and is transcriptionally upregulated in MCF-7 cells upon estrogen treatment. LncRNA1476 has now been fully annotated (transcription start and stop site, 5' cap, polyA tail, and exon/intron structure), and cloned. Molecular analyses indicate that lncRNA1476 plays a critical role in ER-dependent pathway. Collectively, our results suggest that lncRNAs are essential in controlling biological processes.
Supported by a grant from the Cancer Prevention and Research Institute of Texas to S.S.G
Citation Format: Choudhari R, Harrison AL, Carrillo CN, Gadad SS. Role of nucleus-specific intergenic long noncoding RNA-1476 in estrogen-dependent transcription in cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-03-12.
Abstract P2-06-16: New targets in triple negative breast cancer: Role of Oncostatin M receptor pathway
Authors: Alvarez I , Araujo A , Abaurrea A , Rezola R , Urruticoechea A , Lawrie C , Caffarel MM 
Published: May 2019

Abstract
BACKGROUND:Triple negative breast cancer (TNBC) has poor prognosis, lack of targeted therapies and are often refractory to conventional chemotherapy treatments. Therefore, finding new therapeutic targets for those tumours is an unmet need with high clinical impact. In this context, Oncostatin M receptor (OSMR) is a promising therapeutic target as it is over-expressed in this tumour subtype and its activation promotes invasiveness (Guo L, et al. 2013 Oncogene; West NR, et al.2014 Oncogene). We previously showed that OSMR is frequently copy-number gained and over-expressed in squamous cell carcinoma, where it induces migration, invasion and metastasis (Caffarel MM, et al 2013 Journal of Pathology; Caffarel MM, et al 2014 Journal of Pathology; Kucia-Tran JA, et al. 2016 Brit J Cancer; Kucia-Tran JA, et al 2018 Journal of Pathology). We now investigate the role of OSMR in breast cancer progression.
METHODS: To address this issue we use a wide array of tools including in vitro cell cultures and in vivo models. The expression of OSMR pathway was analysed in FFPE samples and large datasets of publicly available breast cancer samples (METABRIC, n=1462; and TCGA, n=547).
RESULTS: OSMR and its ligand Oncostatin M (OSM) are over-expressed in basal tumours, where they associate with shorter overall survival (p=0.015). While OSMR is expressed by breast cancer cells and cancer associated fibroblasts, the main source of OSM seems to be primarily macrophages. OSM treatment of breast cancer cells induces the expression of important mediators of angiogenesis and invasion. Importantly, OSMR activation accelerates tumour onset, tumour growth and metastasis in orthotopic xenografts in nude mice.
CONCLUSIONS: Our results support that OSMR pathway may have an important role in the initiation and progression of breast cancer and that it could be a promising candidate for therapeutic targeting in TNBC. OSMR could be blocked by antibody based inhibition, strategy that has had a major impact on breast cancer.
Citation Format: Alvarez I, Araujo A, Abaurrea A, Rezola R, Urruticoechea A, Lawrie C, Caffarel MM. New targets in triple negative breast cancer: Role of Oncostatin M receptor pathway [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-06-16.
Abstract P2-06-24: Cannabinoid receptors agonist induces lysosome-mediated cell death in TNBC
Authors: Chatterjee N , Das S , Ahiwar D , Mishra S , Kaul K , Ganju R 
Published: May 2019

Abstract
Breast cancer is one of the leading causes of death among women in the United States. Among all the breast cancer subtypes, triple-negative breast cancer (TNBC) is denoted as having the highest rate of mortality due to inefficacious therapy, drug resistance, and high recurrences rate. Despite many therapeutic advances over the past decades, novel therapeutic approaches are required to treat TNBC. Although lysosomes have recently been identified as novel targets in a variety of cancers, not much known about their role in breast cancer especially in TNBC. Due to the altered features of lysosomes in cancerous cells, its functional ability affects cell proliferation, metabolism, adaptation, and autophagy in tumor cells. Thus, the induction of lysosomal membrane permeabilization (LMP) may be used as a novel approach in controlling the aberrant cellular functions in TNBC. Cannabinoid receptor 2 (CB2) is expressed in breast cancer and its agonist JWH-015 has been shown to inhibit TNBC growth and metastasis. However, not much is known about the mechanisms by which JWH015 inhibit growth and metastasis. To investigate JWH015-mediated therapeutic mechanisms, we examined the lysosome-mediated cell death in TNBC cells. We found that JWH015 induces cell death in TNBC cells through lysosomal disruption mechanism. We also showed that JWH-015 treatment increases releases of lysosomal proteins, cathepsin D/B, and autophagy marker LC3B and that leads to activation of apoptotic cell death signaling in TNBC. These alterations result in the formation of autolysosomes to promote LMP. Our findings elucidate the mechanism by which JWH-015 promotes LMP induced autophagy and regulates TNBC cell proliferation. These studies elucidate novel lysosomal-mediated cell death mechanisms through activation of CB2 receptors in TNBC.
Citation Format: Chatterjee N, Das S, Ahiwar D, Mishra S, Kaul K, Ganju R. Cannabinoid receptors agonist induces lysosome-mediated cell death in TNBC [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-06-24.
Abstract P2-07-10: Not presented
Authors: Lee H-B , Kim KE , Ju YW , Jung J-G , Ryu H-S , Lee SB , Lee JW , Lee HJ , Kim M-S , Kwon S , Kim J , Kim C , Moon H-G , Noh D-Y , Ahn S-H , Park I-A , Kim S , Yoon S , Kim A , Han W 
Published: May 2019

Abstract
This abstract was not presented at the conference.
Citation Format: Lee H-B, Kim KE, Ju YW, Jung J-G, Ryu H-S, Lee SB, Lee JW, Lee HJ, Kim M-S, Kwon S, Kim J, Kim C, Moon H-G, Noh D-Y, Ahn S-H, Park I-A, Kim S, Yoon S, Kim A, Han W. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-07-10.
Abstract P2-08-08: Isolated ipsilateral local recurrence of breast cancer: Predictive factors and prognostic impact
Authors: Houvenaeghel G , de Nonneville A , Cohen M , Classe J-M , Reyal F , Mazouni C , Chopin N , Martinez A , Daraï E , Coutant C , Colombo P-E , Gimbergues P , Chauvet M-P , Azuar A-S , Rouzier R , Tunon de Lara C , Murraciole X , Agostini A , Gonçalves A , Lambaudie E 
Published: May 2019

Abstract
Background
Tumour features associated with isolated invasive breast cancer ipsilateral local recurrence (ILR) after breast conservative treatment (BCT) and consequences on overall survival (OS) are still debated. The aim of our study was to examine predictive factors of isolated ILR after BCT with in sano resection and whole breast irradiation as well as the impact of such an ILR on overall survival in a large multi-institutional cohort.
Methods
Patients were retrospectively identified from a large cohort of 23,375 consecutive patients who underwent BCT for invasive breast cancer in 16 cancer centres. End-points were ILR rate and OS. The impact of ILR on OS was assessed through multivariate analysis by logistic regression and Cox model, adjusted on ERs/Grade status (ERs+/Grade 1, ERs+/Grade 2, ERs+/Grade 3 and ERs-) and then on tumour subtypes.
Results
Of 15,570 patients, ILR rate was 3.1%. Cumulative ILR rates differed according to ERs/grade (ERs+/Grade2: HR=1.42, p=0.010; ERs+/Grade3: HR=1.41, p=0.067; ERs-: HR=2.14, p&lt;0.0001), endocrine therapy (HR=2.05, p&lt;0.0001) and age&lt;40-years old (HR=2.28, p=0.005) in multivariate analysis. When multivariate analysis was adjusted on tumour subtype, the latter was the only independent factor. OS-after-ILR was significantly different according to ILR-free intervals (HR=4.96 for ILR-free interval between 2-5-years and HR=9.00 when &lt;2-years, in comparison with ≥5-years).
Impact of free interval time on OS among patients with ILR and among all patients p-valueHRInfSupILRno ILR 1 &lt;2 years0.0172.2551.1594.388 2-5 years0.0012.451.423.89 ≥5 years0.1030.5550.2741.126Tumor subtypesLuminal A G1 1 Luminal A G20.0031.4311.1321.810 Triple negative&lt;0.00012.6992.0553.544 Luminal B ER-&lt;0.00013.1952.4144.229 Luminal B ER+0.021.6081.0762.401 HER2+&lt;0.00012.2791.4523.579
Conclusion
ERs/Grade status, lack of endocrine therapy and tumour subtypes predict isolated ILR risk in patients treated with BCT. Short ILR-free-intervals represent a strong pejorative factor for OS. These results may help selecting initial treatment as well as tailoring ILR systemic chemotherapy.
Citation Format: Houvenaeghel G, de Nonneville A, Cohen M, Classe J-M, Reyal F, Mazouni C, Chopin N, Martinez A, Daraï E, Coutant C, Colombo P-E, Gimbergues P, Chauvet M-P, Azuar A-S, Rouzier R, Tunon de Lara C, Murraciole X, Agostini A, Gonçalves A, Lambaudie E. Isolated ipsilateral local recurrence of breast cancer: Predictive factors and prognostic impact [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-08.