bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P2-16-14: HER2-positive breast cancer: Combined 18F-FDG PET and CGFL/Curie nomogram to predict pathologic complete response after preoperative chemotherapy with trastuzumab
Authors: Vincent Laura , Jankowski Clémentine , Cortet Marion , Arnould Laurent , Ladoire Sylvain , Coudert Bruno , Desmoulins Isabelle , Charron-Barra Céline , Beltjens Françoise , Rouzier Roman , Reyal Fabien , Humbert Olivier , Cochet Alexandre , Coutant Charles 
Published: March 2020

Abstract
Background The aim of this study was to compare the value of 18F-fluorodesoxyglucose positron emission tomography (18F-FDG PET/CT) with CGFL/Curie nomogram to predict a pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in women with human epidermal growth factor 2 (HER2)-positive breast cancer treated by trastuzumab. Methods Fifty-one women with HER2-positive breast cancer treated with trastuzumab plus taxane-based NAC, were retrospectively included from January 2005 to December 2015. For 18F-FDG PET/CT, the analyzed predictor was the maximum standardized uptake value of the primary tumor and axillary nodes after the first course of NAC (PET2.SUVmax). pCR was defined by no residual infiltrative tumor but in situ tumor was accepted. Accuracy of CGFL/Curie nomogram and PET2.SUVmax was evaluated measuring sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV). For each predictor, receiver operating characteristic (ROC) curve was created. To evaluate the correlation between predictors, the Spearman coefficient was calculated. Combined prediction was evaluated testing predictor’s associations. Results For CGFL/Curie nomogram’s performances, Se, Sp, PPV and NPV were respectively: 76% (CI95%: 58-90%), 57% (CI95%: 43-66%), 55% (CI95%: 42-65), 77% (CI95%: 59-90%). For PET2.SUVmax’s performances, Se, Sp, PPV and NPV were respectively: 67% (CI95%: 48-81%), 77% (CI95%: 64-97%), 67% (CI95%: 48-82%), 77% (CI95%: 64-87%). ROC curves for these predictors were similar; the areas under the curve were 0.6 (CI95%: 0.56-0.64) for PET2.SUVmax and 0.55 (CI95%: 0.50-0.59) for CGFL/Curie nomogram. Spearman coefficient was 0.23. Combined prediction was more efficient with Se at 80%, VPN at 76%, Sp at 78% and VPP at 81 %. Conclusions CGFL/Curie nomogram and PET2.SUVmax were two efficient predictors of pCR in patients with HER2-positive breast cancer. Combined prediction has an improved accuracy.
Citation Format: Laura Vincent, Clémentine Jankowski, Marion Cortet, Laurent Arnould, Sylvain Ladoire, Bruno Coudert, Isabelle Desmoulins, Céline Charron-Barra, Françoise Beltjens, Roman Rouzier, Fabien Reyal, Olivier Humbert, Alexandre Cochet, Charles Coutant. HER2-positive breast cancer: Combined 18F-FDG PET and CGFL/Curie nomogram to predict pathologic complete response after preoperative chemotherapy with trastuzumab [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 P2-16-14.
Abstract P2-16-21: Novel use of a precision medicine tool in the neoadjuvant therapy setting
Authors: Beitsch Peter , Whitworth Pat , Lee Laura , Ruiz Antonio , Brown Rick , Gold Linsey , Baron Paul , Patel Rakesh 
Published: March 2020

Abstract
Background: Molecular genomic profiles are increasingly used to guide treatment of refractory cancers and are on the forefront of personalized medicine for select patients. The neoadjuvant chemotherapy (NAC) setting provides a meaningful opportunity to compare genomic profiles to pathologic response. We report profiles to response in a novel multi center registry.
Methods: An ongoing IRB (WIRB) approved registry at 6 community breast practices submitted tumor samples prior to treatment for genomic/proteomic analysis (Paradigm, Phoenix, AZ.) Tumor response and associated molecular profiles were analyzed. The test evaluated over 137 genomic alterations with known actionable variations including mutations, gene-fusions, copy number variations, MRNA expression and protein expression analysis by IHC.
Results: 76 patients were enrolled and 42 have completed treatment including definitive surgery and have reported data as of this date. The vast majority of patients had invasive ductal carcinoma with 16% having triple negative biology and 20% having Her2 biology. Of the triple negative patients with reported surgical results, 42% had a complete response or minimal residual disease, and the remaining 58% had a partial response. Of the patients with HER2 biology, 85% had a complete response and the remaining a partial response. 17% of patients with luminal biology had a complete response; the remaining had only a partial response or progression. Overall, 15 patients had a complete response, 4 had minimal residual disease and the remaining (over 50%) had a partial response, stable or progressive disease. Patients who did not achieve a complete response had multiple molecular aberrations with unique markers not present in patients with PCR. These included markers of known or possible drug resistance (IGFR1, CAIX), poor prognostic markers (TP53, MET, PTEN), biomarkers of response to approved treatment that were not utilized and other markers of potential response and research.
Conclusions: Comprehensive genomic testing may predict resistant biology and provide additional targets for treatment or clinical study. Genomic analysis earlier in the patient’s care path may improve response rates by suggesting modifications in standard protocols or identifying clinical trials as potential first line options. Repeat genomic analysis may also suggest options for targeted adjuvant therapy for residual cancer after neoadjuvant therapy.
Citation Format: Peter Beitsch, Pat Whitworth, Laura Lee, Antonio Ruiz, Rick Brown, Linsey Gold, Paul Baron, Rakesh Patel. Novel use of a precision medicine tool in the neoadjuvant therapy setting [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 P2-16-21.
Abstract P2-17-02: Locoregional therapy targeted at the primary tumour improves overall survival in patients presenting with de novo stage IV metastatic breast cancer: A systematic review and meta-analysis of real-world data with 201598 patients
Authors: Tayeh Salim , Gera Ritika , Chehade Hiba El Hage , Wazir Umar , Kasem Abdul , Mokbel Kefah 
Published: March 2020

Abstract
Background: De novo stage IV metastatic breast cancer is a complex disease that is traditionally treated using systemic therapy. There is mounting evidence that locoregional therapy (LRT), defined as resection of the primary tumour and/or localised radiotherapy, could be associated with survival improvements. We aimed to conduct a meta-analysis to inform decision making.
Methods: Using the PubMed, Cochrane and Ovid SP databases, a literature review and meta-analysis was undertaken to assess whether LRT of the primary tumour in metastatic breast cancer prolongs survival.
Results: 48 studies met the criteria for analysing the efficacy of all locoregional treatments (radiotherapy and/or surgery) and 44 studies were suitable for the analysis of surgery-only treatment of the primary. Studies were analysed for the impact of LRT on survival. All LRT resulted in a significant 32.9% reduction in mortality with LRT (N=48; HR=0.671: 95% CI 0.624-0.721). Primary resection alone resulted in a significant 36.9% mortality (N=44; HR=0.631: 95% CI 0.591-0.674).
Conclusions: This is the largest meta-analysis regarding this question to date. LRT seems to improve overall survival in stage IV disease at initial diagnosis and should be considered in selected patients after a multidisciplinary discussion.
Citation Format: Salim Tayeh, Ritika Gera, Hiba El Hage Chehade, Umar Wazir, Abdul Kasem, Kefah Mokbel. Locoregional therapy targeted at the primary tumour improves overall survival in patients presenting with de novo stage IV metastatic breast cancer: A systematic review and meta-analysis of real-world data with 201598 patients [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 P2-17-02.
Abstract P2-19-02: Circulating osteocalcin-positive cells as a novel diagnostic biomarker for bone metastasis in breast cancer patients
Authors: Cho Sun Wook W , Lee Kyung-Hun , Kim Tae-Yong , Park Serk In , Im Seock-Ah 
Published: March 2020

Abstract
Purpose: Diagnosis of bone metastasis (BM) in breast cancer relies on structural changes of bone. We investigated whether circulating osteocalcin-positivecells (cOC) could detect the incipient and/or progressive BM earlier than image-based diagnostics.
Experimental design: Metastatic breast cancer patients with or without bone metastasis (designated BM+ or BM-) were enrolled and cOC were quantified at baseline by flow cytometry. The progression of BM was evaluated after 18 months. Murine BM models were established by intra-tibial or -cardiac injection of MDA-MB-231 or 4T1 breast cancer cells.
Results: In the baseline analysis, cOC was significantly higher in BM+ than BM- group. In the 18-month follow-up study of BM+ patients (n=63), baseline cOC was significantly associated with BM disease progression. Among BM- patients (n=33), three patients developed new bone metastasis within 18 months and were found to have had higher cOC at baseline. The patients with higher cOC showed shortened BM progression-free survival, compared with those with lower cOC (cutoff=0.045%; P&lt;.001; HR 4.79; 95% CI 2.17-10.56). In murine intra-tibial injection models, cOC significantly increased at an early time-point, even when micro-metastases were evident only by histologic examination but undetectable by bioluminescence imaging. Additionally, in an intra-cardiac injection model, the mice with higher cOC developed BM at an earlier time point, compared with the mice with lower cOC.
Conclusions: cOC is increased in the early phase of breast cancer BM and predict the disease progression. cOC can be a novel biomarker for early diagnosis and progression of BM.
Citation Format: Sun Wook W Cho, Kyung-Hun Lee, Tae-Yong Kim, Serk In Park, Seock-Ah Im. Circulating osteocalcin-positive cells as a novel diagnostic biomarker for bone metastasis in breast cancer patients [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 P2-19-02.
Abstract P3-01-14: N-Myc and STAT interactor regulates STAT5a in mammary development and metastasis
Authors: Samant Rajeev Sharad , Alsheikh Heba A , Metge Brandon J , Chen Dongquan , Wei Shi , Shevde Lalita A 
Published: March 2020

Abstract
Delicate balance between cellular plasticity and differentiation is critically maintained during mammary development. Disruption of this balance leads to breast cancer initiation and metastatic progression. Recent findings from our lab have revealed that N-Myc and STAT Interactor (NMI) protein is decreased in 70% of primary patient specimens with metastatic breast cancer. Mammary specific Nmi knock out mouse model revealed that conditional Nmi loss disrupts luminal differentiation in the mammary gland affecting alveologenesis and prompted the progression of tumors with aggressive metastatic characteristics.
Our studies showed that Nmi is induced at the onset of pregnancy and its expression remains throughout lactation. Furthermore, prolactin stimulation and differentiation of HC11 murine mammary epithelial cells is accompanied by up-regulation of Nmi. STAT5a is one of the downstream effector of prolactin and is essential for differentiation of secretory alveolar epithelium. However, functional relationship of NMI and STAT5a was not known.
Here we present our finding that NMI and STAT5a expression has a direct relationship in normal mammary development as well as in breast primary and metastatic tumor specimens. We demonstrate that loss of Nmi in vivo caused a decrease in STAT5a activity and a subsequent transcriptomic shift in mammary epithelial and breast cancer cells. Detailed examination of STAT5a mammary specific controlled genetic program in the context of transcription profiles of NMI knockout and overexpressing cell lines as well as mammary tumors revealed ISG20, interferon stimulated exonuclease gene 20, as a unique negatively regulated transcript. Here we show that expression of ISG20 is kept in check by NMI by miR17-92 cluster and that ISG20 has a positive influence on tumor progression and metastasis.
Citation Format: Rajeev Sharad Samant, Heba A Alsheikh, Brandon J Metge, Dongquan Chen, Shi Wei, Lalita A Shevde. N-Myc and STAT interactor regulates STAT5a in mammary development and metastasis [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 P3-01-14.
Abstract P3-01-16: Utilizing a decellularized patient-derived xenograft tumor model for the evaluation of triple negative breast cancer
Authors: Wright Maryl , Matossian Margarite , King Connor , Nguyen Khoa , Elliott Steven , Alzoubi Madlin , Martin Elizabeth , Collins-Burow Bridgette , Burow Matthew 
Published: March 2020

Abstract
Triple negative breast cancer (TNBC) is an aggressive and heterogeneous disease with poorer prognoses compared to other breast cancer (BC) subtypes. This is due, in part, to the lack of clinically approved targeted therapeutics. The mechanisms underlying the process of recurrence in TNBC remain elusive. Traditional 2D BC models do not accurately mimic the cell-matrix interactions and extracellular matrix (ECM) composition that are vital to maintaining the tumor microenvironment and are unique to individual patient tumors. Here we introduce and utilize our novel decellularized patient-derived xenograft (PDX) TNBC model, TU-BcX-4IC (“4IC”), to address this knowledge discrepancy. In this study, we seeded TU-BcX-4IC PDX-derived cells onto TU-BcX-4IC PDX decellularized tumor scaffold (“4IC + 4IC scaffold”) and implanted our model into SCID/beige mice. Concordantly, mice were inoculated with TU-BcX-4IC cells mixed with Matrigel and PBS (“4IC + Matrigel”), or PBS alone (“4IC + PBS”). We demonstrate that our decellularized model, along with the injected cells, can form tumors in vivo. We also show that the “4IC + 4IC scaffold” model retains aberrant mitotic figures seen in the original 4IC PDX. However, due to inconsistent tumor growth in the experimental group, optimization of cell seeding onto our decellularized scaffold model is needed to produce consistent tumor propagation in vivo. We compared the number and area of metastases in the lungs and livers excised from the mice. The area and number of lung metastases were lower in mice implanted with “4IC + 4IC scaffold,” albeit not significantly. There was little difference in the area of liver metastases in all groups. The number of liver metastases was lower in the “4IC + Matrigel” and “4IC + 4IC scaffold” groups; however, there was no significance. All groups had a greater propensity to metastasize to the livers. We also compared differences in human and mouse ECM gene expression amongst all groups. Our decellularized scaffold model can be used as a platform to evaluate ECM onco-architecture and composition. The data presented here will help enhance our understanding of the breast tumor microenvironment and elucidate the mechanisms underlying tumorigenesis and recurrence in TNBC.
Citation Format: Maryl Wright, Margarite Matossian, Connor King, Khoa Nguyen, Steven Elliott, Madlin Alzoubi, Elizabeth Martin, Bridgette Collins-Burow, Matthew Burow. Utilizing a decellularized patient-derived xenograft tumor model for the evaluation of triple negative 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 P3-01-16.
Abstract P3-01-21: Functional duality of NUAK2 in breast cancer metastases
Authors: Jia Wang , Jingyan XUE , Jianjing Hou , Bingqiu Xiu , Lun Li , Yayun Chi , Jiong Wu 
Published: March 2020

Abstract
Background: Breast cancer patients with lymph nodes metastasis were proven to have more aggressive biologically phenotypes. This study was aimed to find different biomarker ectopic expression between breast cancer patients' metastatic lymph nodes and primary cancer, and to explore the potential molecular mechanisms.
Method: From our previous research, we selected the pairing samples from primary breast cancer with their early stage lymph node metastasis to carry out differential gene expression profiling. Genes with high expression level in sentinel lymph node metastasis were obtained. Then according to the findings of CRISPR/Cas9 screening and the results in relevant literature and online public database, we decided to investigate the role of NUAK2 in our further research. In vitro and in vivo analyses were carried out to determine the potential mechanisms of NUAK2 in lymph node metastases and prognosis. Results NUAK2 belongs to the AMP-activated protein kinase (AMPK) family, with its members controling protein metabolism, polarity, and overall cellular homeostasis actin cytoskeleton organization. The effect of NUAK2 variant expression in breast cancer metastases remains unknown. In this study, it was found that the expression level of NUAK2 was significantly higher in 5 paired metastatic lymph node than that in primary cancer, using Affymetrix GeneChip® Human Transcriptome Array 2.0. From online public database, higher NUAK2 expression level was markedly associated with better metastasis-free survival in breast cancer patients. The effects of NUAK2 on proliferation were investigated by CCK-8 and IncuCyte ZOOM™ assay, respectively. The results demonstrated that knockdown NUAK2 was able to significantly inhibit the proliferation of breast cancer cells. However, for cancer metastases, it was demonstrated that knock-down of NUAK2 significantly accelerated the migration of breast cancer cells, while overexpression of NUAK2 notably inhibited breast cancer cell migration. When promoting proliferation of breast cancer cells, NUAK2 might involve signal pathways of cell cycle. As for the anti-metastasis function, it would regulate cell adhesion, cell motility and microenvironment.
Conclusion: Our in vitro study demonstrated that NUAK2 has shown reverse effects of tumor cell proliferation and invasion. The interaction of NUAK2 and cancer cells could be an important role in cell proliferation involved in cell cycle signal pathway, and modulate cell mobility by inducing cell-cell detachment. Its molecular mechanism of dual effect in breast cancer need further investigation.
Citation Format: Wang Jia, XUE Jingyan, Hou Jianjing, Xiu Bingqiu, Li Lun, Chi Yayun, Wu Jiong. Functional duality of NUAK2 in breast cancer metastases [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 P3-01-21.
Abstract P3-01-27: Ectonucleotidase ATP hydrolysis facilitates breast cancer bone metastasis
Authors: Shropshire Daniel B , Benavides Jaime , Jiang Jean X 
Published: March 2020

Abstract
Bone is the most common site for breast cancer metastasis. Osteocytes are the most abundant bone cell and can signal nearby cells by releasing ATP through connexin 43 hemichannels. We previously found that this signaling pathway hindered breast cancer growth in bone. In this study, we investigated the role of purinergic signaling on breast cancer bone metastasis in patient samples. Surprisingly, no ATP receptors were differentially expressed in bone metastases compared to other sites. However, enzymes that degrade ATP into adenosine (CD39/ENTPD1 and CD73/NT5E) were upregulated, as was the ADORA3 adenosine receptor (Limma, p=0.037, 0.016, 0.0019, respectively). We next investigated whether this expression signature in primary tumors predicts bone metastasis. In primary ER+ breast cancer, which predominately metastasizes to bone, high expression of these genes is correlated with lower distant metastasis-free survival (HR = 1.97, 1.49, 2.03, logrank p=0.0017, 0.0004, 0.0012). Moreover, this expression pattern is correlated with a bone metastasis signature (Spearman R=0.28, p=1.2 × 10−20). In a pharmacologic screen of 750 cancer cell lines, breast cancer lines and especially ER+ ones, are uniquely sensitive to a pan-adenosine receptor inhibitor (Limma, p=2.9 × 10−5) and ADORA3/2B inhibitor (p=5.4 × 10−5). Our findings suggest that an expression program to convert ATP to adenosine facilitates bone metastasis and begins in the primary tumor. ADORA3 inhibition is proposed as a pharmacologic strategy for preventing or treating bone metastasis. Furthermore, bone metastases should be analyzed in anti-CD39 and CD73 clinical trials.
Citation Format: Daniel B Shropshire, Jaime Benavides, Jean X Jiang. Ectonucleotidase ATP hydrolysis facilitates breast cancer bone metastasis [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 P3-01-27.