bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract IA27: Glioma stem cells: What are they?
Authors: Parada Luis F. 
Published: May 2016

Abstract
We have generated mouse models of GBM by driving loss of function of in the NF1, p53 and Pten tumor suppressors in the adult mouse brain. Using genetic cell labeling and lineage tracing approaches, our models support the hypothesis that stem/progenitor cells are the most likely cells to accumulate mutations over time and become the source of GBM. We have succeeded in reporter labeling the putative “Cancer Stem Cell” population and demonstrate their requirement for effectively mediating endogenous tumor recurrence after chemotherapy and in successfully supporting serial transplantation of tumors in intracranial allografts. The availability of enriched Cancer Stem cells should provide a powerful tool for identifying critical molecular properties and novel therapeutic targets.
Citation Format: Luis F. Parada. Glioma stem cells: What are they? [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr IA27.
Abstract ES4-2: Tailoring chemotherapy
Authors: Ring A 
Published: May 2016

Abstract
Numerous advances have been made in the management of advanced breast cancer over the last decade. Many of these have focused on the development of targeted agents, capitalising on our increased understanding of the molecular pathways involved in breast cancer biology. Nonetheless for many patients the backbone of treatment remains cytotoxic chemotherapy, either as a sole therapy (in those with cancer phenotypes where additional targeted therapy is not indicated) or combined with targeted therapy. Whilst most of the chemotherapy agents indicated in the treatment of advanced breast cancer have been available in the clinic for many years there remain controversies and variations in practice around the use of these standard agents.
This presentation will discuss the indications and factors which should be taken into account in making the choice between combinations as compared sequential single agent chemotherapy. The clinical trial evidence will be overviewed with examples from clinical practice. The continuation of chemotherapy beyond maximal response and the advantages and disadvantages of maintenance chemotherapy will then be discussed. This will lead on to a discussion of whether there is a population of patients in whom metronomic low-dose chemotherapy might be indicated. In the final part of the presentation whether choice of chemotherapy should be influenced by tumour phenotype as defined by estrogen receptor status, HER2 status and the patient's germline BRCA mutation status will be discussed.
At the conclusion of this educational session it is anticipated that the attendees will have a good understanding of the evidence underlying these areas, as well as practical knowledge which will help in clinical practice. It is hoped that better understanding of the optimal use of chemotherapy will maximise the benefit of these agents for our patients: gaining longest possible control of disease with best possible quality of life.
Citation Format: Ring A. Tailoring chemotherapy. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr ES4-2.
Abstract ES7-1: Neoadjuvant endocrine therapy
Authors: Ma CX 
Published: May 2016

Abstract
Neoadjuvant endocrine therapy has become a standard approach in clinical practice to improve the chance of breast conservation in postmenopausal women with locally advanced estrogen receptor positive breast cancer based on results from several neoadjuvant endocrine trials. Although data is limited, neoadjuvant endocrine therapy appears to as effective as chemotherapy in converting mastectomy to lumpectomy. In addition, neoadjuvant endocrine therapy allows an early assessement of tumor responsiveness to endocrine therapy so that adjuvant treatments could be tailored accordingly. Persistent cell proliferation on neoadjuvant endocrine therapy predicts a high risk of early relapse, for whom novel treatment strategies are in great need. In contrast, the Preoperative Endocrine Prognostic Index score of 0 (pathologic T2/3 N0 Ki67 &lt;2.7% ER+) in response to neoadjuvant endocrine therapy is being prospectively evaluated in the ongoing Alliance A011106 (ALTERNATE) as a marker of endocrine sensitive disease, for whom chemotherapy could be avoided. Furthermore, neoadjuvant endocrine trials provide a unique research platform for biomarker studies and the testing of novel therapeutic hypothesis.
Citation Format: Ma CX. Neoadjuvant endocrine therapy. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr ES7-1.
Abstract P1-06-05: The impact of ethnicity on normal breast biology
Authors: Nakshatri H , Anjanappa M , Bhat-Nakshatri P 
Published: May 2016

Abstract
The incidence of/mortality from the most aggressive triple negative breast cancer (TNBC) is higher in African American- (AA) than Caucasian (CA)-women. In contrast, breast cancer in Hispanic-women is generally less aggressive. There is an ongoing debate as to whether AA-women have an increased incidence of TNBCs that have poor outcome or there are unique biological factors in AA-women that promote aggressive biology. Through unique approaches, we provide evidence for distinct biology in the normal breasts of CA-women, AA-women, and Hispanic-women. Using resources from the Komen Normal Tissue Bank and a primary cell culturing system that enabled propagation of normal epithelial cells of different lineages including mature-luminal, luminal-progenitor, and stem cells from different ethnic groups, we have identified a subpopulation of CD44high/CD24- cells that are unique to AA-women (p=0.0001). This AA-women-specific subpopulation expressed higher levels of Collagen 3A1, Collagen 5A2, CTNNB1 (β-Catenin of Wnt), FOXC2, and ZEB1 compared to common CD44+/CD24+ subpopulation in every breast. Gene expression pattern in the AA-specific CD44high/CD24- population showed marked similarity to gene expression pattern in the recently described PROCR+ multi-potent mammary stem cells. Indeed, the breast epithelial cells of AA-women were enriched for PROCR-positive stem cells compared to CA-women or Hispanic-women (p=0.015). In contrast to cells from CA- and AA-women, cells isolated from the healthy breast of Hispanic-women displayed mostly differentiated features as they were enriched for CD49f-/EpCAM+ and CD271-/EpCAM+ mature cells. Cells from CA-women, AA-women and Hispanic-women are currently being immortalized to determine the cell types that are preferentially immortalized in each of these ethnic groups. These results suggest ethnicity-dependent differences in Wnt, extracellular matrix, and epithelial to mesenchymal transition (EMT) signaling in normal breast epithelial cells and differences in the proportion of cells that are susceptible to immortalization/transformation.
This work is supported by Susan G. Komen for the Cure to HN (SAC110025).
Citation Format: Nakshatri H, Anjanappa M, Bhat-Nakshatri P. The impact of ethnicity on normal breast biology. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-06-05.
Abstract P1-09-10: Mammographic density: Its inherent epidemiology in 12000 women from 22 diverse countries
Authors: McCormack VA 
Published: May 2016

Abstract
The International Pooling Project on Mammographic Density Consortium
Background: Over the past 25 years, the epidemiologic knowledge for mammographic density (MD), as a strong marker of breast cancer risk, has expanded greatly, aided by the availability of mammograms in countries with wide-scale mammography-based breast cancer screening programs. The known epidemiology of this breast-tissue specific marker is thus that of women in high incidence countries, and not of that in countries with lifestyles that are characterized by very different life-long hormonal influences, especially during the reproductive years. The International Pooling Project on Mammography Density (IPPMD) aimed to examine the epidemiology of MD internationally, to benefit from breast cancer risk and breast cancer risk factor heterogeneity.
Methods: From diverse breast cancer risk populations, IPPMD sought to include samples of 200 premenopausal and 200 postmenopausal general population women for which risk factor data and mammograms, not taken for symptomatic reasons, were available. To date we have included 11447 women from 22 countries, consisting of 40 ethnicity and location-specific population groups. 5 to 6 countries were included in each of Europe, Africa and the Middle East, Asia and the Americas. Populations not previously studied in terms of MD include South Africa, Kenya, Turkey, Egypt and Brazil.
Digitized/digital films for every woman were anonymised, transferred to the study and read using Cumulus 6 by 3 readers, to obtain standardized quantitative and comparable MD estimates across the entire sample. Readers were blind to all woman and study/country identifiers. Normal errors regression models were used to analyse square root percent density and absolute dense area, after standardizing reader-specific values to a single reader's distribution.
Results: All risk factor data and MD readings have recently been pooled. Initial findings are as follows. Mean percent MD and absolute dense area varied over 2-fold between the 40 population groups, after adjusting for age and BMI. There is striking consistency in several epidemiologic features of MD across all population groups, including the rate of decline of density at both pre and post-menopausal ages and the decline associated with the menopausal transition. We are exploring to what extent these and other factors such as menarche, parity, age at first birth and breastfeeding, account for between population-group differences in MD.
Conclusions: This international perspective provides a valuable insight to the epidemiology of MD worldwide.
Citation Format: McCormack VA. Mammographic density: Its inherent epidemiology in 12000 women from 22 diverse countries. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-09-10.
Abstract P1-14-21: Predictive factors of pathologic complete response of HER2-positive breast cancer after preoperative chemotherapy with trastuzumab: Development of a specific predictor
Authors: Jankowski C , Guiu S , Cortet M , Hudry D , Arnould L , Charon-Barra C , Desmoulins I , Rouzier R , Fumoleau P , Coudert B , Reyal F , Coutant C 
Published: May 2016

Abstract
Purpose: The aim of this study was to assess the M.D Anderson Cancer Center / Gustave Roussy Institute (MDACC/IGR) nomogram in predicting pathologic complete response (pCR) to preoperative chemotherapy in a cohort of HER2 tumors treated with preoperative chemotherapy with trastuzumab. Then, we combine clinical and pathological variable associated with pCR into a new nomogram specific of HER2 tumors treated by preoperative chemotherapy with trastuzumab.
Methods: Data from 270 patients treated with preoperative chemotherapy with trastuzumab at Curie Institute and at Georges Francois Leclerc Cancer Center were used to assess MDACC/IGR nomogram and then to develop a nomogram for pCR based on multivariate logistic regression. Model performance was quantified with respect to calibration and discrimination.
Results: The IGR/MDACC was not accurate to predicting pCR in HER2 tumors treated by preoperative chemotherapy with trastuzumab with poor discrimination (AUC=0,54, IC [0,51-0,58]) and poor calibration (p=0,01). After uni and multivariate analysis, the new pCR nomogram was based on T stage (TNM), hormonal receptor status, and ki67(%). The model had a good discrimination 0,74 (IC95% : [0,70-0,79]) and a good calibration (p=0,93).
Conclusion: To our knowledge, this is the first nomogram to predict pCR in HER2 tumors treated by preoperative chemotherapy with trastuzumab. To ensure exportability, the model need to be evaluate with a external validation set.
Citation Format: Jankowski C, Guiu S, Cortet M, Hudry D, Arnould L, Charon-Barra C, Desmoulins I, Rouzier R, Fumoleau P, Coudert B, Reyal F, Coutant C. Predictive factors of pathologic complete response of HER2-positive breast cancer after preoperative chemotherapy with trastuzumab: Development of a specific predictor. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-14-21.
Abstract P1-16-08: Inhibition of β-catenin pathway to overcome endocrine resistance in breast cancer
Authors: Won HS , Lee KE , Lee KM , Nam EM , Mun Y-C , Seong C-M , Lee SN 
Published: May 2016

Abstract
Background: It is well known that Wnt/β-catenin signaling pathway is involved in hormone receptor negative breast cancer, especially triple-negative breast cancer. In the case of hormone resistant breast cancer cells, they rarely showed hormone receptor expression. So we aimed to investigate whether the β-catenin pathway becomes activated in endocrine-resistant breast cancer cells and inhibition of β-catenin pathway can overcome endocrine resistance.
Methods: We have established an MCF-7-derived tamoxifen-resistant cell line (TamR) by long-term culture of MCF-7 cells with gradually increasing 4-hydroxytamoxifen concentration till 3μM. The levels of protein expression and mRNA transcripts were determined using western blot analysis and real-time quantitative PCR. The transcriptional activity of β-catenin was measured using luciferase activity assay. We used ICG-001 as inhibitor of β-catenin transcription activity.
Results: The expression of estrogen receptor was significantly decreased in TamR cells. On the other hand, the expressions of HER2 and EGFR were increased in TamR cells than in control cells. The active (uncomplexed form) β-catenin level was increased in TamR cells, and also showed a significantly increased β-catenin transcriptional activity. The ICG-001, small-molecular inhibitor of Wnt/β-catenin pathway, treatment significantly reduced β-catenin transcriptional activity in TamR cells. The ICG-001 reduced cell viability fo TamR cells which showed resistance to tamoxifen by 65.3%, and also inhibited target gene cyclin D1 expression. The combination of ICG-001 and mTOR inhibitor, rapamycin reduced cell viability of TamR cells by 81.7% and there was an additive effect of two drugs as a combination index of 1.022.
Conclusions: The β-catenin pathway is activated in endocrine-resistant breast cancer cells and inhibition of that pathway would be a new therapeutic strategy which overcomes endocrine resistance in breast cancer.
Citation Format: Won HS, Lee KE, Lee KM, Nam EM, Mun Y-C, Seong C-M, Lee SN. Inhibition of β-catenin pathway to overcome endocrine resistance in breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-16-08.
Abstract P2-02-13: EpCAM-independent enrichment approach for isolation of circulating tumor cells (CTCs) in breast cancer - What can be found in the EpCAM-depleted fraction?
Authors: Fehm T , Schneck H , Gierke B , Pawlak M , Templin M , Niederacher D , Neubauer H 
Published: May 2016

Abstract
Circulating tumor cells (CTCs) are the potential precursors of metastatic disease. Many assays have been established for the enumeration of CTCs. However, major limitations include the reliance on the expression of the cell surface marker epithelial cell adhesion molecule (EpCAM). These approaches may not detect CTCs that either express no/low levels of EpCAM or undergo epithelial-to-mesenchymal transition (EMT). We present an enrichment strategy combining different antibodies specific for surface proteins and extracellular matrix (ECM) components to capture EpCAMneg cell lines and EpCAMneg CTCs from EpCAM-depleted breast cancer blood samples. Expression of proteins (Trop2, CD49f, cMet, CK8, CD44, ADAM8, CD146, TEM8, CD47) was verified by immunofluorescence on EpCAM-positive (e.g. MCF7, SKBR3) and -negative (MDA-MB-231) breast cancer cell lines; antibodies and ECM proteins (e.g. hyaluronic acid (HA), collagen I, laminin) were further spotted in a single- and multi-arrayed format onto glass slides (Schott, NEXTERION® AL) and coupled to immunomagnetic beads (Dynabeads/Adembeads). Tumor cell adhesion of EpCAMpos/neg cell lines was visualized by Coomassie/MitoTracker; EpCAMneg CTCs enriched via functionalized Adem-/Dynabeads were identified by immunofluorescence staining for anti-pan-Cytokeratin(CK)-FITC/anti-CD45 AF647/DAPI and quantified manually by microscopy. Regarding cell lines, marginal binding of EpCAMneg MDA-MB-231 cells to EpCAM-antibodies could be observed. Efficient adhesion/capturing of EpCAMneg cells could be achieved via HA and immobilized antibodies against CD49f and Trop2. By analyzing 29 EpCAM-depleted fractions from 25 metastatic breast cancer patients, we were able to identify EpCAMneg CTCs in 69% of the samples [range 1-24] applying Trop2, CD49f, cMet, CK8 and/or HA magnetic enrichment. Accessorily, EpCAMneg dual-positive (CKpos/CD45pos) cells could be traced in 28 out of 29 samples [range 1-480]. Herein, we demonstrate an enhanced enrichment strategy to optimize capturing of EpCAMneg CTCs by targeting various cell surface antigens with antibody mixtures and ECM components. Thereby, potential relevant CTCs can be gathered and subjected to subsequent molecular analysis.
Citation Format: Fehm T, Schneck H, Gierke B, Pawlak M, Templin M, Niederacher D, Neubauer H. EpCAM-independent enrichment approach for isolation of circulating tumor cells (CTCs) in breast cancer - What can be found in the EpCAM-depleted fraction?. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-02-13.
Abstract P2-05-04: The development of the metastatic site pattern during time in different subtypes of breast cancer
Authors: Lindman H , Haji A 
Published: May 2016

Abstract
Introduction:
The most common metastatic sites in breast cancer (BC) are bone, lung and liver, but metastases to CNS, other visceral organs, skin and lymph nodes are often seen. Depending on the BC subtypes there are data on different patterns of the metastatic sites. However, little is known about the risk for development of new metastatic sites during the course of the disease. Possibly, the development of new sites of the disease is signs of novel intrinsic capabilities of the metastases that might be explained by new mutations. Primary aim of this study was to examine the metastatic pattern and development of new metastatic sites in different BC subgroups.
Materials and Methods:
This is a population based cohort study covering patients in the Uppsala County treated for metastatic BC (MBC) from 2009 to 2014. The information was collected from the real-time treatment registry and medical records. The distant sites were classified as bone, lung/pleura, soft tissue, other visceral and CNS and the timing was defined in steps starting with M1 when patient first was defined as having MBC. The BC subtypes were defined as luminal A, luminal B, HER2-positive (HER2) and triple negative (TN) based on immunohistochemical analyses. The metastatic patterns at death were compared with the patterns at M1.
Results:
Totally 391 patients with MBC with a median age of 65 years were included. Median disease-free survival was 51 months. The development of metastases in new sites occurred in up to three distinguished steps, with median lag times of 22, 13 and 14 months, respectively. The median survival from M1 was 69, 37, 64 and 17 months for the luminal A, luminal B, HER2 and TN subtypes.
The frequencies of metastases in in first (M1) and subsequent sites (next) in each subtypeM1%/next%BoneLung/pleuraSoft tissueLiverOther visceralCNSLuminal A74/431/2122/1020/2816/151/4Luminal B66/1144/1438/327/3216/54/10HER246/1536/2042/1719/2810/1319/31TN27/746/1751/629/017/1117/17The sums of the figures represent the risk for metastases in a certain site at death.
Conclusion:
The pattern of metastatic sites at M1 in different BC subtypes does not represent the pattern for development of new metastatic sites during the course of the disease. We observed a significantly different risk for developing new metastatic sites depending on subtypes, most obvious regarding liver metastases. TNBC seemed to have less ability to develop new metastatic sites.
Citation Format: Lindman H, Haji A. The development of the metastatic site pattern during time in different subtypes of breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-05-04.