bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-05-14: Multiscale computational modeling of breast cancer invasion: Towards a predictive patient-based tool
Authors: Trucu D , Thompson A , Chaplain MAJ 
Published: August 2014

Abstract
Background: Understanding the mechanisms of the growth and spread of cancer cells in the human breast and providing effective treatment continues to remain a significant challenge. Cancer cell invasion of breast tissue plays a pivotal role in the metastatic cascade through complex, coupled dynamics of the constituent processes occurring over a range of spatial and temporal scales, ranging from genetic events through intracellular signaling pathways through cell-matrix interactions to tissue scale changes.
Method: While most previous computational modeling has been carried out at the level of a single spatial or temporal scale, the work presented here has developed a novel multiscale modeling and computational simulation framework. Formulated in both two and three spatial dimensions, this approach is based on a new type of multiscale moving boundary computational model that explores the crucial role that matrix degrading enzymes, secreted by individual cancer cells (micro-scale) along the invasive edge of the tumour, play in the overall dynamics of the tissue-scale invasion (macro-scale).
Results: The computational simulation results we have obtained reveal a rich variety of cancer invasion patterns that emerge in the vicinity of a primary breast cancer. In the presence of heterogeneous tissue, our computational simulation results show well-defined “lobular” and “fingering” invasion patterns, consistent with the spread of a breast carcinoma, and which remain robust with respect to any changes made in the model parameters. These patterns are found to be compatible with respect to both the dynamic heterogeneity of cancer cell macro-scale distributions and to the evolution of the heterogeneity of the surrounding breast tissue.
Conclusions: By exploring the dynamics of the molecular processes of matrix degrading enzymes and of tissue-scale spatio-temporal cancer tissue evolution, this novel multiscale computational modeling framework faithfully replicates the cancer invasion process. Development of this computational tool should allow pre-operative breast cancer patient data to be used to predict the extent of breast cancer invasion and hence the extent of surgical resection.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-05-14.
Abstract P1-13-07: Association Between Delayed Initiation of Adjuvant Chemotherapy and Survival in Breast Cancer: A Single-institution Study and A Systematic Review and Meta-analysis
Authors: Yu K-D , Fan L , Yang C , Shao Z-M 
Published: August 2014

Abstract
Objective: Adjuvant chemotherapy (AC) improves survival among patients with operable breast cancer. However, the effect of delay in AC initiation on survival is unclear. We performed a single-institution data analysis and a systematic review and meta-analysis to determine the relationship between time to AC and survival outcomes.
Methods: PubMed, EMBASE, Cochrane Database of Systematic Reviews, and Web-of-Science databases (before March-20, 2012) were searched to identify relevant eligible studies. An additional retrospective analysis including 1,408 patients from the prospectively maintained database of Shanghai Cancer Center was performed and results were also included. Hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS) from each study were converted to a regression coefficient (β) and its standard error corresponding to a continuous representation per 4-week delay of AC. Individual adjusted β were combined using a fixed-effects or random-effects model depending on heterogeneity.
Results: We included 8 eligible studies with 10 independent analytical groups involving 21,221 patients, 1 prospective observational study, 2 secondary analyses in randomized trials (4 analytical groups), and 5 hospital-/population-based retrospective studies. In our single-institution study, every 4-week delay in initiation of AC significantly decreased OS (HR = 1.38; 95% confidence interval [CI], 1.03–1.87) and DFS (HR = 1.35; 95% CI, 1.08–1.69) after adjustment for other prognostic variables. The overall meta-analysis demonstrated that a 4-week increase in time to AC was associated with a significant decrease in both OS (HR = 1.20; 95% CI, 1.03–1.39; random-effects model) and DFS (HR = 1.21; 95% CI, 1.08–1.36; fixed-effects model). One study caused a significant between-study heterogeneity for OS (p = 0.001; I2=74.1%); after excluding that single study, there was no heterogeneity (p = 0.345; I2=11.1%) and the HR was more significant (HR = 1.24; 95% CI, 1.14–1.35; P &lt; 0.001; fixed-effects model). Our single-institution data did not fundamentally influence the positive outcomes, since the HR of OS was 1.17 (95% CI, 1.00–1.37; random-effects model) after removing our study. No evidence of publication bias was observed either in OS or in DFS.
Conclusion: The present meta-analysis suggests that longer time to AC was associated with worse survival in breast cancer patients.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-13-07.
Abstract P1-13-09: A multicenter randomized study comparing the dose dense G-CSF-supported sequential administration of FEC followed by docetaxel versus paclitaxel as adjuvant chemotherapy in women with axillary lymph node positive breast cancer.
Authors: Mavroudis D , Malamos N , Boukovinas I , Kakolyris S , Kourousis C , Athanasiadis A , Ziras N , Makrantonakis P , Polyzos A , Christophylakis C , Georgoulias V 
Published: August 2014

Abstract
Purpose: To compare the efficacy of dose dense docetaxel versus paclitaxel following FEC as adjuvant chemotherapy in node positive early breast cancer.
Patients and treatment: Women 18–75 years old with histologically confirmed HER2-negative invasive breast carcinoma surgically resected with at least one infiltrated axillary lymph node and absence of metastatic disease were randomized to receive 4 cycles of fluorouracil (700mg/m2), epirubicin (75mg/m2), cyclophosphamide (700mg/m2) followed by 4 cycles of either docetaxel (75mg/m2) or paclitaxel (175mg/m2). All chemotherapy cycles were administered every 14 days with G-CSF support. Stratification was based on menopausal status, number of involved nodes and hormone receptor expression. The primary endpoint of the study was to compare the disease-free survival (DFS) at 3 years and 239 patients were scheduled to enroll on each arm.
Results: Between 2004–2007, 481 women were randomized and received FEC followed by docetaxel (arm A; n=240) or paclitaxel (arm B; n=241). The median age was 55 years in both arms, premenopausal status 31.3% versus 32.8%, more than 10 involved axillary nodes in 12.9% versus 12.4%, histological grade 3 tumor in 36.3% versus 35.3% and hormone receptor negative disease in 14.6% versus 12% of patients in arms A and B, respectively. After a median follow up of 56.3 and 55.6 months (p = 0.3) for arms A and B, respectively, there were 42 (17.5%) versus 47 (19.5%) disease relapses (p = 0.5) and 20 (8.3%) versus 22 (9.1%) disease-related deaths (p = 0.7), respectively. The 3-year DFS rates were 88.1% versus 87.3% for arms A and B, respectively. Toxicity included grade 2–4 neutropenia in 31% versus 21% (p = 0.01), thrombocytopenia 3.5% versus 0.8% (p = 0.06), febrile neutropenia 2.1% versus 1.2% (p = 0.5), diarrhea 3.7% versus 2.5% (p = 0.4), neurotoxicity 2.9% versus 4.6% (p = 0.3) of patients in arms A and B, respectively. There were no toxic deaths.
Conclusion: The dose dense administration with G-CSF support of FEC followed by either docetaxel or paclitaxel as adjuvant chemotherapy in women with node positive early breast cancer is well tolerated and results in a similar 3-year DFS rate.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-13-09.
Abstract P1-13-12: [bold]The adjuvant PANTHER study - A randomized comparison between dose-dense and tailored epirubicin (E), cyclophosphamide (C) and docetaxel (D) vs. standard dose 5-fluorouracil (F), epirubicin (E), cyclophosphamide (C) and docetaxel – First report on q
Authors: Brandberg Yvonne , Bengtsson Nils-Olof , Greil Richard , Möbus Volker , Malmström Per , Johansson Hemming , Andersson Harald , Hellström Mats , Gnant Michael , von Minckwitz Gunter , Bergh Jonas ,   the Swedish Breast Cancer Group,   the Austrian Breast-Colorectal Study Group and German Breast Cancer Group
Published: August 2014

Abstract
Withdrawn by Author
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-13-12.
Abstract P1-14-21: High antitumoral activity of neoadjuvant chemotherapy (NCT) with weekly paclitaxel + capecitabine and trastuzumab in patients with locally advanced HER2+ breast cancer (HER2+ LABC): Preliminary results.
Authors: Augereau P , Raro P , Verriele V , Delva R , Abadie-Lacourtoisie S , Ceban T , Paillocher N , Valo I , Maillart P , Soulie P 
Published: August 2014

Abstract
Background: The addition of targeted agent (trastuzumab and/or pertuzumab and/or lapatinib) to NCT has dramatically improved pathological complete response rate (pCR) against HER2+ LABC. Early introduction of trastuzumab may be determinant as suggested by adjuvant trials while anthracycline free chemotherapy limits the risk of cardiotoxicity.
Treatment and methods: From 01/2006 to 08/2011, 55 patients with HER2+ LABC (defined by 3+ or SISH+, confirmed by an expert pathologist) were considered for this regimen: paclitaxel 80mg/m2/wk D1/8/15 q4wk; capecitabine (fixed dose) 1500 mg bid, 5d/wk, 3 wk/4; trastuzumab (T) 4 mg/kg loading dose (D1 cycle1), 2mg/kg D1/8 and 4mg/kg D15 q4wk, for a total of 6 cycles (1 cycle = 4 weeks). Additional trastuzumab (6mg/kg) was given q3wk for 9 cycles. Mastectomy was considered for multifocal CIC, extended DCIS, initial inflammatory tumor and post operative radiotherapy was given if indicated.
Patient characteristics: Median age: 58 years [28–84]; tumor stage II/III: 53%/47%; T1-2: 44%, T3: 36%, T4ac/d: 4%/16%; N0: 42%; median tumor clinical size: 4,6 cm [1–10]; grade III: 51%, HR−/HR+: 51%/49%. All patients were CT naïve.
Results: Median follow-up was 27 months [9–74]. Clinical activity: major response (CR+PR) was observed in all patients (84% cCR). Pathological activity: 63,5% of patients achieved a tumor and nodal pCR (Sataloff TANA or NB, without residual invasive tumor cells), 22% had residual DCIS. According to hormonal receptor status (HR), pCR was 89% in HR−, 37% in HR+. Surgery was conservative in 37 patients (67%). 2 patients had locoregional recurrence (T4dN3, T3N1, both pCR and HR−).
Toxicity (NCI-CTC scale):. Only 6 patients stopped either paclitaxel or capecitabine before the 6th cycle (1 at Cycle 3, 2 at cycle 5, and 3 at cycle 6). Main toxicities were: mucositis grade (gr) ½: 34%; diarrhea gr½: 27%; hand foot syndrome gr ½: 40%, gr 3: 9%; peripheral neuropathy gr ½: 39%, gr 3: 6%; asthenia gr ½: 47%, onychopathy gr½: 33%; gr 3: 6%; neutropenia gr 3: 9%, no febrile neutropenia. Two patients have a grade 2 reversible cardiotoxicity (LVEF &lt; 50 %)
Conclusion:. This NCT provided high pCR, specially in the HR- subgroup with a very favourable toxicity profile and merits further exploration.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-14-21.
Abstract P2-01-14: circulating tumor cells in breast cancer exhibit dynamic changes in epithelial and mesenchymal cell composition
Authors: Yu M , Bardia A , Wittner BS , Stott SL , Smas ME , Ting DT , Isakoff SJ , Ciciliano JC , Wells MN , Shah AM , Concannon KF , Sequist LV , Brachtel E , Sgroi D , Baselga J , Ramaswamy S , Toner M , Haber DA , Maheswaran S 
Published: August 2014

Abstract
Epithelial to mesenchymal transition (EMT) has been postulated to contribute to the migration and dissemination of cancer cells, but supporting histopathological evidence is limited. We used a microfluidic device to isolate circulating tumor cells (CTCs), combined with multiplex fluorescent RNA-in-situ hybridization (ISH) and RNA sequencing, to quantify and characterize EMT in breast cancer cells within the bloodstream. Whereas only rare (0.1–10%) cells in the primary tumor expressed both mesenchymal and epithelial markers, such biphenotypic as well as purely mesenchymal cells were enriched among CTCs, across all histological subtypes of breast cancer. Analysis of the therapy response in 8 patients suggest an association of mesenchymal CTCs with disease progression. In an index patient followed longitudinally, fluctuation in epithelial and mesenchymal states was observed as a function of initial response and subsequent resistance to therapy. Mesenchymal markers were predominant in clusters of tumor cells, many of which had adherent platelets. Finally, RNA sequencing of mesenchymal CTC clusters identified TGF-B and other EMT-related signatures, which were absent from more epithelial CTCs. FOXC1, a known regulator of EMT, was abundantly expressed in mesenchymal CTCs and was detectable within localized regions of the primary breast tumor. Together, these data support a role for EMT in the blood-borne dissemination of breast cancer and point to the dynamic nature of this cell fate change.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-01-14.
Abstract P2-02-03: The Collagen Receptor Endo180: A Metastatic Plasma Marker In Breast Cancer Modulated By Bisphosphonate Treatment
Authors: Sturge J , Caley MP , Purshouse K , Fonseca A-V , Rodriguez-Teja M , Kogianni G , Waxman J , Palmieri C 
Published: August 2014

Abstract
Purpose: To establish whether the collagen remodelling receptor, Endo180, should be given consideration as a useful plasma marker in metastatic breast cancer.
Patients and Methods: Analysis of MCF-7 and MDA-MB-231 cell conditioned medium validated the anti-human (39.10) monoclonal antibody as suitable for the detection of soluble Endo180 in plasma. Eighty-seven breast cancer patients with early primary, locally advanced and metastatic disease were included in the study. Correlations between Endo180, CA 15–3 antigen (MUC1; mucin 1) and bisphosphonate treatment were investigated.
Results: Endo180 was elevated in metastatic compared to early breast cancer (P &lt;.0001) and was able to differentiate locoregional disease and visceral and/or osseous metastasis (P = .0005). In combination CA 15–3 antigen (cut-off: 28 U/mL) and Endo180 (relative plasma level cut-off range: 0.95–1.65) had sensitivity of 94–97% and specificity of 52–68%. Endo180 levels were significantly higher in patients who were treatment naive (2.17 ± 0.82, N = 13) compared to those previously (1.82 ± 0.33, N = 5) or currently (1.37 ± 0.74, N = 24) receiving bisphosphonates (P = .011). In the bisphosphonate naive setting (N = 57) the combination of Endo180 (relative plasma level cut-off range: 0.95–1.65) and CA 15–3 antigen (cut-off: 28 U/mL) had a sensitivity of 87–92% and specificity of 72–79%.
Conclusion: Endo180 is a plasma marker with high sensitivity in metastatic breast cancer that can be modulated by bisphosphonate treatment.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-02-03.
Abstract P2-04-01: Development of mouse breast cancer models based on induced cancer stem cells (iCSC).
Authors: Takamoto Y , Onishi N , Kai K , Saya H 
Published: August 2014

Abstract
Breast cancer is one of the leading causes of death in women worldwide. To develop novel therapeutic approaches for the refractory cases, the mouse models which recapitulate the tumor tissues biologically and pathologically similar to human breast cancer are required. Although xenograft models of established cell lines in immune-deficient mice are frequently used for preclinical experiments, such xenograft models are not sufficient because the heterogenous structure based on the microenvironment and the intrinsic characteristics of cancer cells is not correctly formed.
In this study, we have established induced cancer stem cells (iCSC) from normal mouse mammary stem/progenitor cells through minimal required genetic manipulations and generated mouse breast cancer models by inoculating the iCSCs in the mammary fat pads. Initially, we established iCSC by introducing the H-RasV12 into Ink4a/Arf-knockout mammary stem/progenitor cells and this iCSC formed tumor similar to human triple negative breast cancer in mouse. This finding suggested that two genetic events, an activation of oncogenic signal and a tumor suppressor inactivation, are required for generating the breast cancer iCSC.
Anaplastic Lymphoma Kinase (ALK) gene, which encodes a receptor tyrosine kinase, was reported to be amplified and/or overexpressed up to 86% of patients in inflammatory breast cancer, and pleiotrophin (PTN), which is a physiological ligand for ALK, was also shown to be highly expressed in about 60% of human breast cancers. Therefore, we hypothesized that ALK pathway is involved in tumorigenesis of breast cancers and, then, attempted to generate iCSC by using ALK gene. Interestingly, we found that one of the naturally occurring mutations of ALK is sufficient for generating iCSC and tumor formation in vivo without any prior tumor suppressor inactivation. The ALK-induced iCSCs developed highly aggressive breast cancers in mice. Furthermore, the tumor formation was significantly suppressed when the ALK-induced iCSCs were generated by using mammary stem/progenitor cells derived from mouse deficient in CD44 which is a CSC marker. We have recently revealed a role of CD44, in particular that of a variant isoform (CD44v), in the protection of CSCs from high levels of oxidative stress derived from both tumor cells and their microenvironment (Cancer Cell 19: 387–400, 2011; Cancer Res 72: 1438–1448, 2012; Nat Commun 3: 883, 2012). We will discuss the underlying mechanism of ALK-induced tumorigenesis and a role of CD44 in the CSC functions.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-04-01.
Abstract P2-05-02: Clinical significance of microRNA regulator Lin28 expression in patient with early breast cancer
Authors: Park S , Shin YK , Song BJ , Chae BJ , Jung SS , Choi Y-L 
Published: August 2014

Abstract
Lin28 is an RNA-binding protein that is highly expressed in human embryonic stem (ES) cells. It can facillatate the reprogramming of human somatic cells to pluripotency with other stem cell marker proteins (Oct4, Nanog and Sox2). Lin28 regulates the processing of microRNAs including let-7 (Mirlet7) and translation of specific subset of cell cycle-related genes such as IGF-2, OCT4. Recently, it has been suggested that Lin28 expression may contribute to breast cancer metastasis in an animal model (Dangi-Garimellaet al., 2009).
To define clinical impact of Lin 28 in breast cancer, we investigated Lin28 expression in tumors from patients with early breast cancer who underwent curative resection of tumor.
To define prognostic impact of Lin 28 in breast cancer, we investigated Lin28 expression in patients with early breast cancer who underwent curative resection of tumor. In all, 950 slides from paraffin-embedded tissue were available for analysis by Lin28 expression by immunohistochemistry (IHC), and 78 cases (13.2%) were identified as Lin28-positive. Lin28 positivity was significantly associated with more advanced stage (P &lt; .001), lymph node involvement (P&lt; .001), absence of estrogen receptor expression (P = .002), negative progesterone receptor expression (P = .017), HER2 overexpression (P&lt; .001), higher histologic grade (P = .008), and higher tumor grade (P = .012). The Lin28 positive patients with early breast cancer demonstrated substantially poorer relapse free survival (Lin28+ positive vs. Lin28−(P = 0.013) and trends toward poorer overall survival.
Taken together, a sub-population of breast cancer with Lin28 expression is significantly associated with aggressive tumor phenotype and poor clinical outcome.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-05-02.
Abstract P2-05-09: Identification and validation of a miRNA signature associated with breast cancer progression
Authors: Waters PS , Dwyer RM , Kerin MJ 
Published: August 2014

Abstract
Introduction: MiRNAs are aberrantly expressed in both the circulation and tissue of patients with breast tumours, however little is currently known about the relationship between circulating and tissue miRNAs. The aim of this study was to quantify circulating and tumour tissue miRNA expression in a murine model of breast cancer and identify novel circulating markers of disease progression.
Materials and Methods: Athymic nude mice (n = 20) received either a mammary fat pad (n = 8, MFP), or subcutaneous (n = 7, SC) injection of MDA-MB-231 cells. Controls received no tumour cells (n = 5). Tumour volume was monitored weekly and blood sampling performed at weeks 1, 3 and 6 following tumour induction (total n=60). Animals were sacrificed at week 6 and tumour tissue (n = 15), lungs (n = 20) and enlarged lymph nodes (n = 3) harvested. RNA were extracted from all samples (n = 98) and relative expression of miRNAs previously associated with tumour progression were quantified using RQ-RCR. A microRNA array was also preformed comparing animals with early (weeks 1, n=5) versus late (week 6, n=5) disease and results were analysed using RQ-PCR in all blood samples (n = 60). Reverse transcription for the relevant targets and endogenous controls was carried out and expression was quantified using RQ-PCR.
Results: MiR-10b expression was significantly higher in MFP compared to SC tumours (p &lt; 0.05), with the highest levels in diseased lymph nodes (p &lt; 0.05). MiR-10b was undetectable in the circulation. MiR-221 expression was significantly increased in tumour tissue (p &lt; 0.001). MiR-195 and miR-497 were significantly decreased in tumour tissue (p &lt; 0.05), and also in the circulation of animals 3 weeks following tumour induction (p &lt; 0.05). At both tissue and circulating level, a significant correlation was observed between miR-497 and miR-195 (r = 0.61, p &lt; 0.001; r = 0.41, p &lt; 0.01 respectively). Microarray analysis revealed the level of 47 miRs to be significantly changed between week 1 and week 6 as disease progressed in a murine model, 10 of which (miR A-J) were significantly altered and internally validated within the murine model.
Conclusions: This study highlights the importance of miRNAs in breast cancer, with each displaying distinct roles in circulation and tissue. Novel circulating miRNAs which have never previously been associated with breast cancer have been identified, with quantification of circulating levels in breast cancer patients currently ongoing.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-05-09.