bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-20-21: The use of intraoperative ultrasound and guidewire placement to obtain low re-excision rates and increased accuracy of excision in impalpable breast lesions at the Cambridge Breast Unit
Authors: Wignarajah Primeera , Papalouka Vasiliki , Forouhi Parto 
Published: March 2020

Abstract
INTRODUCTION: Increasingly we are dealing with more and more impalpable breast lesions thanks to screening programmes, chemotherapy and in situ disease. There are various techniques already employed for assisting in surgery for impalpable lesions such as radioactive and magnetic markers. All of these have limitations and are only useful in surgery. Ultrasound can be used in clinic and theatre to locate tumours and sonographically visible markers. In our experience in the Cambridge breast unit we have found it is more satisfactory to use guidewires that are intraoperatively or preoperatively placed using ultrasound guidance. This allows for direct approach to the lesion at the same time limiting the dissection and volume of resection. The guidewire allows tactile feedback and helps with precision and accuracy of the excision as reflected in the specimen weights. In this study we look at the outcomes of intraoperatively and preoperatively placed guidewires using ultrasound for impalpable breast lesions between 2015 -2018 in the Cambridge Breast Unit. The primary outcomes are re-excision rate and average specimen weights.
METHODS: Patients undergoing breast conservation surgery for impalpable lesions from 01/01/2015 to 30/07/2018 were included. Data was collected retrospectively from our electronic records system EPIC and analysed.
RESULTS The results were divided into intraoperative localisations and preoperative localisations. A total of 441 lesions in 415 patients were included in this study.
Preoperative localisationIntraoperative localisationNumber of patients193222Number of lesions210231*Re-excision rate per patient %19.2%14.0%Specimen weight per patient (grams)39.4g24.2g*Fishers exact 0.24 (NS)
CONCLUSION: Impalpable lesions can be successfully localised using ultrasound guidance and a guidewire both intraoperatively and preoperatively with good outcomes. Intraoperative localisation has lower re-excision rates and specimen weights in our study as well as many other benefits for the patient and surgeon. We have looked into how easily and quickly we can train ultrasound naïve trainees in this technique and have achieved good results.
Citation Format: Primeera Wignarajah, Vasiliki Papalouka, Parto Forouhi. The use of intraoperative ultrasound and guidewire placement to obtain low re-excision rates and increased accuracy of excision in impalpable breast lesions at the Cambridge Breast Unit [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 P1-20-21.
Abstract P1-21-02: Distinct methylation and copy number alteration patterns in phyllodes tumors of the breast and its mimics
Authors: Muenst Simone , Vlajnic Tatjana , Soysal Savas Deniz , Frank Stefan , Hench Jürgen 
Published: March 2020

Abstract
Background: Phyllodes tumor (PT), a rare fibroepithelial neoplasm of the breast, poses a significant diagnostic challenge in breast pathology, as there are no generally accepted histological criteria or cutoffs to unambiguously differentiate PT variants (benign, borderline, malignant) and fibroadenomas (FA) of the breast. In recent years, genome-wide DNA methylation analysis has gained wide interest as an objective tool to distinguish all sorts of neoplasms based on their individual methylation signatures. For brain tumors, methylation-based classification already outperforms classification by conventional histology and has led to changes in the WHO tumor classification.
Materials and Methods: We have so far analyzed fresh frozen as well as formalin-fixed, paraffin-embedded tissue samples of PT (n=31) and FA (n=2) on Illumina Infinium Methylation EPIC bead chips. The resulting data were preprocessed, normalized, mapped to the genome and converted into beta values. Top differentially methylated probes were determined by the calculation of standard deviations across the dataset. Such filtered sets of methylation beta values were then compared by a dimension reduction algorithm alongside TCGA methylome datasets as well as collections from GEO and the entire diagnostic database of our institute (n=14342). In parallel, the genome-wide copy number alterations were calculated from array data for each case.
Results: In analogy to other tumor entities included in our reference cohort (brain tumors, sarcomas, carcinomas, melanomas), PT and FA of the breast show distinct DNA methylation patterns that contain a breast-specific signature as well as tumor-derived patterns. Their methylomes are distinct from breast adenocarcinoma as well as from healthy breast tissue. Two distinct groups within the PT/FA spectrum were identified so far: One group contains a high fraction of histologically malignant PT and is enriched for complex copy number alterations while the other group, also containing the currently two included fibroadenomas and, features less prominent to no copy number variants and a higher similarity to the overall normal breast tissue methylation signature.
Conclusion: The distinct methylation signatures of the histological PT/FA spectrum will not only allow the diagnostic discrimination of PTs from histological mimics such as FA or carcinomas, but will also enable the distinction of benign, borderline and malignant PTs, thus paving the way to an optimized prognostic patient stratification and clinical management.
Citation Format: Simone Muenst, Tatjana Vlajnic, Savas Deniz Soysal, Stefan Frank, Jürgen Hench. Distinct methylation and copy number alteration patterns in phyllodes tumors of the breast and its mimics [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 P1-21-02.
Abstract P1-21-06: Deregulated immune pathway associated with palbociclib resistance in breast cancer preclinical models: Integrative analysis of genomics and transcriptomics
Authors: Moon Yong Wha , Lee Eunbyeol , Hwang Sohyun , Pandey Kamal , Park Nahee , Hur Jin , Cho Young Bin , Kim Seung Ki , Lee Seung Ah , An Hee-Jung , Sohn Joohyuk 
Published: March 2020

Abstract
Background: Recently CDK4/6 inhibitors are being widely used to treat advanced HR-positive breast cancer. Despite promising clinical outcomes, almost all patients eventually acquire resistance to CDK4/6 inhibitors. Hence, understanding the mechanisms of acquired resistance to CDK4/6 inhibitors is crucial to develop alternate treatment strategy. Therefore, we screened genes associated with palbociclib resistance through genomics and transcriptomics in breast cancer preclinical models. Methods: We generated palbociclib-resistant cell lines, MCF7-PR and T47D-PR by exposing MCF7 and T47D cells to palbociclib for over 9 months. After confirming the acquired resistance through in vitro assays, we performed whole exome sequencing (WES) and mRNA microarray to compare genomic and transcriptomic landscape between palbociclib-sensitive and resistant cells. Real-time PCR was performed to confirm differentially expressed genes. Results: Microrray analysis revealed 651 differentially expressed genes (DEGs) (fold change ≥2) by comparing MCF7 vs. MCF7-PR cells. WES also revealed 107 mutated genes by comparing T47D vs. T47D-PR cells. Further, GO annotation of both the DEGs and mutated genes found deregulation of immune pathway commonly in MCF7-PR and T47D-PR (FDR&lt;0.25). Representatively, activated type I interferon pathway was notable in MCF7-PR cells with annotation of the DEGs. By real-time PCR, IRF9 and SP100 were commonly increased in the resistant cells (MCF7-PR, T47D-PR) compared to each sensitive counterpart. Besides, STAT1, IFI27, IFIT2, IFIT3, and XAF1 were increased in the MCF7-PR compared to MCF7, STAT2 was also increased in the T47D-PR compared to T47D. Regarding mutations found in resistant cells, MUC4 (in MCF7-PR) and MUC16 (in T47D-PR) mutations were annotated as immune pathway including immune response activating cell surface receptor signaling or O-glycan processing, et al. Besides, RB1 mutation was detected in T47D-PR cells. Conclusions: Deregulated immune pathway was found to be associated with palbociclib resistance in preclinical breast cancer models. Further studies are warranted to evaluate whether immune pathway may be a therapeutic target to overcome CDK4/6 inhibitor resistance.
Citation Format: Yong Wha Moon, Eunbyeol Lee, Sohyun Hwang, Kamal Pandey, Nahee Park, Jin Hur, Young Bin Cho, Seung Ki Kim, Seung Ah Lee, Hee-Jung An, Joohyuk Sohn. Deregulated immune pathway associated with palbociclib resistance in breast cancer preclinical models: Integrative analysis of genomics and transcriptomics [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 P1-21-06.
Abstract P2-04-03: The roles of fucosylation in promoting tumorigenic signaling in breast cancer
Authors: Snyder Kara , Ren Hui , Lester Daniel , Fang Bin , Koomen John , Lau. H Eric 
Published: March 2020

Abstract
Fucosylation is an important form of protein glycosylation involved in the progression of cancer. Aberrant fucose and fucosylated serum protein/oligosaccharide levels have been previously described in breast cancer (BC). Fucosylation has been reported impact proliferation and key signaling pathways (e.g., ERK1/2, p38 MAPK, and E-selectin) in human breast invasive ductal carcinoma. However, precise roles and functions of fucosylated proteins function in BC remain largely unclear. In our preliminary analyses, we performed immunofluorescent lectin staining of BC tissue microarrays and cell lines grown in vitro and found that fucosylation is increased in BC vs. normal breast tissues. To study the functional contributions of fucosylation to BC biology, we either pharmacologically or genetically suppressed fucosylation in BC cell lines. The treated or modified cell lines were characterized for their ability to grow/proliferate in 2D or 3D, as well as on adhesion to extracellular matrix (ECM). We observed that inhibiting fucosylation blunted BC cell proliferation, particularly in 3D, and attenuated adhesive capacity. To determine the mechanism(s) underlying the biological functions of fucosylation in BC cells, we performed parallel fucosylated and phosphoproteomic mass spectrometric analyses on BC cells that were either pharmacologically or genetically inhibited for fucosylation to identify: (i) all fucosylated proteins in BC cells and (ii) signaling pathways that comprise directly fucosylated proteins and that are significantly altered in activity (phosphorylation). All filtered hits were subject to Ingenuity Pathway Analysis. Thirteen signaling pathways were identified in common amongst both pharmacologically or genetically modulated BC groups. These pathways clustered into the following 3 major functional groups: cell-cell/cell-matrix contact, RNA processing, and endosomal/phagosomal dynamics. The most fucosylated proteins included integrins. We validated the direct fucosylation of integrins and further dissected the molecular and functional contributions of fucosylation to integrin signaling in vitro and in vivo in mouse models of breast cancer. Our data identify new roles for fucosylation in regulating key signal transduction pathways in BC. How integrin signaling and BC cell biology is regulated by fucosylation, as well as potential clinical utility of fucosylated integrins for BC, will be discussed.
Citation Format: Kara Snyder, Hui Ren, Daniel Lester, Bin Fang, John Koomen, Eric Lau. H. The roles of fucosylation in promoting tumorigenic signaling in breast cancer [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 P2-04-03.
Abstract P2-04-05: Loss of Ste20-like kinase induces a basal/stem-like phenotype in HER2-positive breast cancers
Authors: Al-Zahrani Khalid N , Abou-Hamad John , Pryce Ben , Cook David P , Hodgins Johnathan , Labreche Cedrik , Robineau-Charette Pascale , de Souza Christiano , Bell John , Auer Rebecca , Ardolino Michele , Vanderhyden Barbara , Schramek Daniel , Sabourin Luc 
Published: March 2020

Abstract
Over the past two decades, the mammalian Ste20-like kinase (SLK) has been characterized for its role in regulating cellular migration, proliferation and apoptosis in fibroblasts and myoblasts. In mammary epithelial cells, SLK has been shown to be required for efficient epithelial-to-mesenchymal transition and to be activated downstream of the HER2/Neu-oncogene to control chemotactic cellular migration. Here, we assessed the role of SLK in HER2/Neu-induced mammary tumorigenesis in vivo. As SLK is activated downstream of HER2/Neu, we hypothesized that the loss of SLK would significantly delay tumor progression in a mouse model of HER2-positive breast cancer. As we have shown that global attenuation of SLK kinase activity results in embryonic lethality, a conditional SLK knockout mouse model was generated. To study the role of SLK in HER2-positive breast cancer, we crossed these conditional SLK knockout mice with mice expressing HER2/Neu linked to Cre recombinase in the mammary luminal epithelium. Unexpectedly, we have demonstrated that conditional deletion of SLK significantly accelerates Neu-induced mammary tumor onset and decreases overall survival. SLK deletion results in the induction of Sox10 which drives mammary stem/progenitor activity and cooperates with HER2/Neu to drive tumor growth. Using the Cancer Genome Atlas, we have supported previous findings and validated Sox10 as a potential biomarker of the Triple-negative Breast Cancer subtype. Furthermore, we have uncovered that SLK deletion results in enhanced activation of AKT. We provide evidence that Sox10 induction requires signaling through a novel AKT/Sox9-dependent pathway following SLK deletion. Taken together, our data suggests that SLK may be required to maintain cells in a fully differentiated state and that loss of SLK in HER2/Neu-induced breast cancer drives a more basal/stem-like phenotype through the induction of Sox10.
Citation Format: Khalid N Al-Zahrani, John Abou-Hamad, Ben Pryce, David P Cook, Johnathan Hodgins, Cedrik Labreche, Pascale Robineau-Charette, Christiano de Souza, John Bell, Rebecca Auer, Michele Ardolino, Barbara Vanderhyden, Daniel Schramek, Luc Sabourin. Loss of Ste20-like kinase induces a basal/stem-like phenotype in HER2-positive breast cancers [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 P2-04-05.
Abstract P2-05-06: Nuclear STING localization induces chemoresistance in breast cancer
Authors: Cheradame Laura , Guerrera Chiara , Judde Jean-Gabriel , Goffin Vincent , Cairo Stefano 
Published: March 2020

Abstract
Efficient DNA damage repair (DDR) is crucial for a cell as aberrant repair can create deleterious mutations and genomic instability while unrepaired damage leads to cell apoptosis. Cells with altered DDR are more inclined to develop a variety of diseases, including cancers Cancer therapies including radiotherapy and chemotherapy rely on double strand break (DBS) formation to drive the killing of rapidly cycling tumor cells. As efficient DNA repair pathways can enable tumor cells to survive treatment-induced DNA damage, the identification of new actors participating in efficient DDR will help design alternative therapeutic approaches. Here we report that the well-known DNA sensor of innate immunity Stimulator of Interferon Genes (STING) is directly involved in the modulation of DSB repair efficiency in breast cancer cells. STING partly resides at the inner membrane of the nucleus where it interacts with core proteins of DNA-damage complexes and promotes its assembly with chromatin. STING silencing decreases DNA repair and cell viability, while STING overexpression protects cancer cells from genotoxic treatment. STING involvement in DNA repair is independent of the canonical STING-triggered pro-inflammatory response. In line with this observation, while overall STING expression level is positively correlated with favorable outcome in breast cancer patients, high STING expression in breast and ovarian cancer patients treated with adjuvant chemotherapy is associated with poor prognosis. This newly-identified function of STING elucidates a cell autonomous tumor-promoting mechanism complementary and independent from its well-documented role in tumor immunosurveillance.
Citation Format: Laura Cheradame, Chiara Guerrera, Jean-Gabriel Judde, Vincent Goffin, Stefano Cairo. Nuclear STING localization induces chemoresistance in breast cancer [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 P2-05-06.
Abstract P2-08-14: Trends in the incidence of breast cancer following the radiological accident in Goiânia, Brazil: A 25-year analysis
Authors: Rocha Marina E , Rahal Rosemar MS , Freitas-Junior Ruffo , Correa Rosangela S , Rodrigues Danielle CN , Martins Edesio , Soares Leonardo R , Oliveira Jose C 
Published: March 2020

Abstract
Background: The largest radiological accident to occur in any urban area happened in a Brazilian state capital city in 1987 to the detriment of the population and the environment. One major concern regarding deleterious effects in the population was a possible increase in breast cancer incidence rates, since the literature shows that exposure of an individual to ionizing radiation is one of the risk factors for cancer. This study analyzed trends in the incidence of breast cancer over the 25-year period following the radiological accident. Methods: This ecological, population-based study was conducted to determine the incidence of breast cancer in female residents of Goiânia, Goiás, Brazil, between 1988 and 2012. The data were collected from the Goiânia population-based cancer registry. Crude and age-standardized incidence rates were calculated. The Joinpoint software program was used to calculate annual percent changes (APC) in the incidence of breast cancer. Results: Overall, 7,365 new cases of breast cancer were identified, with an annual crude incidence rate of 23.09/100,000 women in 1988 and of 71.65/100,000 women in 2012. The age-standardized incidence rate was 35.63/100,000 women in 1988 and 65.63/100,000 women in 2012. Analysis of the APC showed a significant annual increase of 4.8% in the incidence between 1988 and 2005 (p&lt;0.0001) followed by stabilization in 2005-2012, with an APC of -3.5% (p=0.1). Conclusion: There was an increase in the incidence of breast cancer in the female residents of Goiânia, Goiás in the first 17 years of evaluation (1988-2004) followed by a period of stabilization until 2012.
Keywords: breast cancer; epidemiology; incidence; age group; Goiânia; Brazil.
Table 1. Annual percent change in the age-standardized incidence rate of female breast cancer by age in the city of Goiânia, Goiás, Brazil between 1988 and 2012.Age Group (years)Trend 1 (Years)APC^*(95%CI)pTrend 2 (Years)APC ^*(95%CI)p≤391988-20075.53.9 - 7.20.0012007-2012-7.0-15.3 - 20.140 - 491988-20054.63.6 - 5.60.00012005-2012-3.7-6.5 - -0.80.000150 - 691988-20046.34.6 - 80.00012004-2012-3.4-6.5 - -0.30.0001≥701988-20120.9-0.1 – 1.90.1–---^Significance: p &gt;0.05; * Annual percent change (APC); * Coefficient of the incidence per 100,000 women; CI: Confidence interval.
Citation Format: Marina E Rocha, Rosemar MS Rahal, Ruffo Freitas-Junior, Rosangela S Correa, Danielle CN Rodrigues, Edesio Martins, Leonardo R Soares, Jose C Oliveira. Trends in the incidence of breast cancer following the radiological accident in Goiânia, Brazil: A 25-year 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 P2-08-14.
Abstract P2-08-25: The 5-years conditional disease free survival and overal survival for breast cancer patients in Korea
Authors: Ahn Jee Hyun , Nam Seok Jin , Kim Seok Won , Lee Jeong Eon , Chae Byung-Joo , Lee Se Kyung , Ryu Jai Min , Yu Jonghan 
Published: March 2020

Abstract
Background: Most of breast cancer patients survive for a long-term period. The existing assessment of survivors’ prognosis has had some limitations in breast cancer because it is based on an evaluation at the time of diagnosis. Conditional survival reflects change over time after diagnosis and treatment of cancer. Conditional disease-free survival (CDFS) and conditional overall survival (COS) can provide more accurate prognosis to breast cancer patients. In this study, we aimed to determine 5-years CDFS and COS according to disease-free period after diagnosis and treatment of breast cancer in Korea. Method: We retrospectively reviewed clinical data of 5664 patients aged 16 to 86 who underwent curative surgery for breast cancer between January 2000 and December 2008 at Samsung Medical Center, a single tertiary hospital in Korea. The CDFS and COS rates were based on cumulative DFS and OS estimates up to 15 years using the Kaplan-Meier method. Results: At baseline, each 5-years DFS and OS were 88.0% and 93.8%. For patients who kept disease free status from 1 to 9 years after surgery, the 5-years CDFS rates were calculated as 88.7%, 90.7%, 91.6%, 91.1%, 91.5%, 91.0%, 89.5%, 86.1% and 86.1%, respectively. The 5-year COS rates of the patients who had survived from 1 to 9 years after surgical treatment were calculated as 92.6%, 92.1%, 91.2%, 91.0%, 89.4%, 85.6%, 80.7%, 75.3%, and 73.0%, respectively. Conclusion: Our study showed that 5-years CDFS and COS for most patients who have breast cancer in Korea seemed to be good prognosis for a long time. However, cancer recurrence tended to occur after a long period postoperatively. Further study is required to identify risk factors associated with recurrence after several years in Korean breast cancer patients.
Citation Format: Jee Hyun Ahn, Seok Jin Nam, Seok Won Kim, Jeong Eon Lee, Byung-Joo Chae, Se Kyung Lee, Jai Min Ryu, Jonghan Yu. The 5-years conditional disease free survival and overal survival for breast cancer patients in Korea [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 P2-08-25.