bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Relevance of Early Disseminated Breast Cancer Cells Depends on Their Cytokeratin Expression Pattern.
Authors: Effenberger K. , Borgen E. , Bartkowiak K. , zu Eulenburg C. , Brors B. , Kaaresen R. , Nesland J. , Pantel K. , Naume B. 
Published: December 2010

Abstract
Background: The factors determining the clinical relevance of disseminated tumor cells (DTC) in breast cancer patients are largely unknown. Here we compared the specificity and clinical performance of two anti-cytokeratin(CK) antibodies frequently used for DTC detection, namely A45-B/B3 (A45) and AE1/AE3 (AE). Additionally we explored the CK gene expression patterns in primary breast tumors.Methods: Specificities of antibodies A45 and AE for selected CKs were assessed by 2-DE western blot analysis. Using these antibodies bone marrow aspirates from 391 breast cancer patients (M0, pT1-3, pN0-3) were screened for the presence of DTC. To obtain prognostic information, patients were followed up over a median of 83 months for time to relapse and 99 months for time to death. Two breast cancer patient datasets (Oslo (n=123), and van de Vijver et al. (NEJM 2002; n=295)) were analysed for CK primary tumor gene expression patterns and grouped by hormone receptor (HR) status of the primary tumors. T-tests and hierarchial clustering analyses were applied.Results: AE detected CK5, CK7, CK8, and CK19, whereas A45 recognized CK7 and CK18. In total, 24 of 391 patients (6.1%) were DTC-positive for A45, and 41 (10.5%) for AE. Although concordance between the two antibodies was 84.4%, overlap among positive cases was only 3.2%. DTC-positivity with AE and A45 was more frequent in patients of higher nodal status (p=0.019 and p=0.036, respectively). Nearly all patients with A45-positive DTC had hormone receptor-positive tumors (23/24), while detection of AE-positive DTC was more frequent among hormone receptor negative patients (p=0.006). Clear differences in primary tumor CK expression patterns between HR+ and HR- tumors were detected in both datasets. Compared to HR- tumors, CKs up-regulated in HR+ tumors were CK8 and 18, in addition CK19 in two datasets, whereas e.g. CK5, CK6, CK7, CK14, CK15, CK16, and CK17 were significantly down-regulated.Survival analyses of all patients revealed shorter distant disease-free survival (p=0.039) for patients with A45-positive DTC, whereas the prognostic relevance of AE-positive DTC was restricted to node positive patients.Conclusion: The clinical utility of immunocytochemical DTC detection depends on the anti-CK antibody used, which may reflect the complex CK composition of DTC. Tumor CK expression patterns and their correlation to antibody-sprecific DTC detection will further be explored by A45- and AE- staining of corresponding patient samples.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3021.
Clinical and Prognostic Features of Infiltrating Lobular Carcinoma of the Breast in a Korean Series.
Authors: Lee J. , Park B. , Park S. 
Published: December 2010

Abstract
Introduction: Infiltrating lobular carcinoma (ILC) is the second most common histological type of invasive breast cancer (IBC) and accounts for 10% of all IBCs. ILC differs from IDC in many respects including age of patients, tumor size and increased frequency of multifocality and bilaterality. But, the outcome of ILC remains unclear. Therefore, we studied the clinical features and prognosis of patients with ILC and infiltrating ductal carcinoma (IDC). Methods: We analyzed data from 3716 breast cancer pts who were were treated at the Yonsei University Health System between 1984 and 2005. Median follow time is 74 months. The patients were categorized as having ILC or IDC. Results: 95(2.3%) tumors were classified as ILC, 3621 (89.4%) as IDC. In analysis there were no differences of age, tumor size, nodal status and stage between ILC and IDC. However, patients with ILC were significantly more likely to have estrogen positive (79.7% for ILC vs 62.6% for IDC, p=0.003) and HER-2 negative tumors (83.6% for ILC vs 70.8% for IDC, p=0.038) compared to patients with IDC. The frequency of bilateral breast cancers was higher for patients with ILC than for patients with IDC (ILC: 6.8% vs. IDC: 3.5%, p=0.013). The systemic recurrence and local recurrence rates for ILC were similar to IDC. However, the sites of systemic recurrence were different. IDC more commonly metastasized lung than IDC (36.5% for IDC vs 9.1% for ILC). ILC more commonly metastasized to bone and the ovaries than IDC (bone: 72.7% for ILC vs 36.5 % for IDC, ovary: 18.2% for ILC vs 0% for IDC). there were no statistically significant differences in DFS and OS between ILC and IDC. The 5-year DFS was 87.6% for ILC and 78.7% for IDC.(p=0.174) The 5-year OS was 93.6% for ILC and 85.5% for IDC.(p=0.104) Conclusion: In the results of this study, the incidence of ILC was quite low in Korean breast cancer patients. ILC showed different histologic features as bilateral involvement, ER positivity, HER-2 negativity and systemic recurrence sites compared to IDC. But the prognosis of ILC was similar to that of IDC.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3036.
High Nuclear Expression of CXCR4 Is Associated with Metastases and Decreased Survival in Hormone Sensitive Breast Cancer.
Authors: Cronin P. , O'Connell F. , Wang J. , Redmond H. 
Published: December 2010

Abstract
Introduction: CXCR4 chemokine receptor and its specific ligand SDF-1alpha are thought to play an important role in breast cancer metastases. High levels of SDF-1alpha in the common destination organs of metastasis are thought to attract CXCR4-positive tumour cells.Aim: The aim of the study was to test whether CXCR4 expression in the primary tumour can indicate breast cancer with high likelihood of metastasising.Methods: Tissue slides were prepared from the paraffin embedded primary tumours of breast cancer patients. CXCR4 expression was detected using immunohistochemistry assessed by a pathologist. Disseminated tumour cells (DTC's) were detected in the bone marrow samples of patients taken at the time of surgery using anti-HEA/FITC-conjugated antibody and flow cytometry. All other clinicopathological features of the patients were also compiled.Results: CXCR4 expression was assessed in one hundred and ten patients. They had a mean age of 57.18 years and a median follow up of 84 months (range 4 – 108). 72.6% of patients had a T2 or a T3 tumour. The majority were hormone sensitive, 80.9% and Her2/neu negative, 76.1%. Disseminated tumour cells were found in the majority of patients, 85.5%, but 57.2% had greater that 1000 DTC's/100,000. There was no correlation found between cytoplasmic staining for CXCR4 and the clinicopathological features of the tumours including DTC's. High nuclear staining was associated significantly with decreased overall and disease free survival, p&lt;0.041 and p&lt;0.025. Tumours with high nuclear staining were significantly more likely to be hormone sensitive, tubulo-lobular tumours [p&lt;0.008, p&lt;0.0349], from older, post-menopausal women [p&lt;0.081, p&lt;0.018]. There was no correlation between her2/neu and CXCR4 expression. Disseminated tumour cells and lymph node metastases were not associated with nuclear staining but these tumours were more likely to develop distant metastases, p&lt;0.034.Conclusion: High nuclear expression of CXCR4 was significantly associated with hormone sensitive breast cancers and development of distant metastases. These patients had decreased overall and disease free survival. Our results show CXCR4 has an important role in breast cancer metastases and has both prognostic and therapeutic potential.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3037.
Association between the Thr431asn Polymorphism of the Rock2 Gene and Breast Cancer.
Authors: Kalender M. , Demiryürek S. , Oztuzcu S. , Kizilyer A. , Demiryürek A. , Sevinc A. , Dikilitas M. , Yildiz R. , Camci C. 
Published: December 2010

Abstract
Background: The objective of this study was to analyze the genotype distributions and allele frequencies for Threonine431Asparagine (Thr431Asn) and Arginine83Lysine (Arg83Lys) polymorphisms of the Rho kinase2 (ROCK2) gene among the breast cancer patients.Material and Methods: In this case-control study, 223 patients with breast cancer were recruited and divided into two groups according to metastases (n=128) and without metastases (n=95). Genomic DNA from the patients and the control cases (n=150) was analyzed by real-time PCR using a Light-Cycler.Results: Neither genotype distributions nor the allele frequencies for the Arg83Lys polymorphism showed a significant difference between the groups. Although no marked changes was observed with no metastasis group, a statistically significant association was found between the control and metastatic group for the Thr431Asn polymorphism of the ROCK2 gene. Further analysis revealed that there were marked associations of this polymorphism with bone, liver, and lung metastases. Homozygous carriers of the Thr431Thr genotype were more frequent among the metastatic patients (39.8%) than among controls (26.0%; P =0.0485). There was also an increase in Thr431 allele (60.5% in patients vs 51.7% in controls) and decrease in Asn431 allele frequencies (48.3% in control vs 39.5% in patients) in metastatic groups (P =0.0356). Progesterone and estrogen receptor negativity was more frequent among metastatic patients carrying a Thr431 allele when compared to the nonmetastatic group.Discussion: Our resulsts are the first to demonstrate that Thr431Asn polymorphism of the ROCK2 gene could be a risk factor for the metastases of the breast cancer, and may help in predicting the prognosis.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3038.
Prognostic Significance of Placenta Growth Factor (PlGF)-1 and PGF-2 Expression in Human Breast Cancer.
Authors: Escudero-Esparza A. , Martin T. , Mansel R. , Jiang W. 
Published: December 2010

Abstract
Background: Placenta growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGf) family, a group of angiogenic growth factors important in cancer development. Over-expression of PlGF is known to be associated with pathological angiogenesis. Recently, PlGF has been shown to have 4 isoforms, -1, -2, -3 and -4. This current study examined the expression of PlGF-1 and -2 in human breast cancer and how changes in expression of these isoforms may be linked to prognosis of the disease.Materials and Methods: Breast cancer primary tumours (n=114) and matched background tissue (n=30) were processed for RNA extraction. RNA was reversed transcribed and quantified before analysis by Q-PCR. The results were expressed as copy number of transcript/50ng RNA and standardised using β-actin. Statistical analysis was carried out using student t test (mean±SD) and Mann-Whitney U test (median/IQR) where appropriate. Immunohistochemistry was also carried out on a number of matched background and tumour sections.Results: Analysis of patients with a 10 year follow-up showed that transcript levels of PlGF-1 were increased in node positive tumours when compared to node negative (104.2±52.2 versus 52.5±13.6, respectively, but this did not reach significance(p=0.34). Prognostic indicators (NPI status, TNM status and grade of tumour) were not associated with significant changes in levels of PlGF-1. Moreover, there was no difference in expression with overall ER status of tumours; however, PlGF-1 was significantly increased in ERβ positive tumours (median values ERβ-ive and ERβ+ive (14.10 vs 68.75 respectively, p=0.014). Most interestingly, there was a significant increase in PlGF-1 expression in patients with poor outcome (median values patients remaining disease-free 16.5, patients who died from breast cancer 78.2, p=0.03). In comparison, the PGF-2 isoform showed little change in expression between tumour and background samples. However, Immunohistochemistry demonstrated a marked increased in PGF-2 expression in tumour sections (staining intensity (mean±SD): Background 102.05± 46.65 vs Tumour 172.85±40.33, n=20, p=0.0001).Conclusions: We can conclude from this data that there is a differential expression of the PlGF isoforms in human breast cancer. Inappropriate expression of PlGF isoforms may play a role in human breast cancer progression.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3041.
Association of Proliferating Macrophages with High Grade, Hormone Receptor Negative Breast Cancer.
Authors: Tonlaar N. , Campbell M. , Garwood E. , Khramtsov A. , Moore D. , Au A. , Baehner F. , Huo D. , David M. , Oluwasola O. , Odetunde A. , Tretiakova M. , Li S. , Gong C. , Tonner E. , Fridlyand J. , Falusi A. , Mcgrath M. , Gray J. , Olopade O. , Esserman L. 
Published: December 2010

Abstract
Macrophages, a key cell in the inflammatory cascade, have been associated with poor prognosis in cancers, including breast cancer. Tumor associated macrophages (TAM) have also been shown to play a role in invasion and metastases. In this study, we investigated the role of a subset of macrophages known as proliferating macrophages (promacs) in breast cancer. We examined the relationship between promacs and clinico-pathologic characteristics such as tumor size, grade, lymph node metastasis, hormone receptor status, molecular subtype, and survival. This study was conducted at two independent institutions (University of California, San Francisco and University of Chicago) using two independent cohorts of patients with breast cancer. Formalin-fixed, paraffin-embedded sections and/or tissue microarrays were double-stained with anti-CD68 (a macrophage marker) and anti-PCNA (a proliferation marker) antibodies. The number of total macrophages as well as promacs per high power field were counted. Molecular subtypes were determined from gene expression array analyses. Outcomes were available for a subset of the cases and Kaplan Meier survival curves were generated.Tumor tissue from two different cohorts of patients with breast cancer were stained and analyzed at two independent institutions. In both studies, promac density was significantly correlated with higher grade, hormone-receptor negative tumors, and a basal-like subtype. In contrast there was no correlation between numbers of promacs and tumor size, stage, or number of involved lymph nodes. The presence of increased promacs was a significant predictor of survival in these treated patients. Proliferating macrophages are more abundant in high grade tumors, and predict a worse outcome, independent of stage and grade. These findings, corroborated at two independent institutions, suggest that the presence of promacs is associated with tumor progression and increased promac density may serve as a prognostic indicator for poor outcomes. Novel therapies that are able to target and halt the activity of promacs may be a promising strategy for the treatment of promac rich tumors.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3042.
Adverse Clinico-Pathological Features in Breast Cancer Patients under the Age of 35.
Authors: Babar M. , Garvin J. , Quinn L. , Dunne B. , Griffin M. , Kennedy J. , Boyle T. , Connolly E. 
Published: December 2010

Abstract
IntroductionBreast cancer in younger patients is a unique disease entity, associated with aggressive biologic phenotype and poorer prognosis. The aim of this study was to analyse age as a prognostic factor in pre-menopausal breast cancer specifically in regards to pre-menopausal patients under the age of 35.MethodsA 7 year prospective audit of pre-menopausal patients presenting to the symptomatic breast clinic in St. James's Hospital between 2001 and 2008 was conducted. The Clinico-pathological features of pre-menopausal patients presenting under the age of 35 versus over 35 where compared. All cancer diagnoses were discussed at the breast multidisciplinary conference, and all clinico-pathological treatment details and follow-up information were entered by a full-time data manager.ResultsPre-menopausal patients under the age of 35 (n=55) were more likely to present with higher grade (p&lt;0.05), oestrogen receptor negative (p&lt;0.05), HER-2 receptor negative (p&lt;0.05) and stage IV disease (p&lt;0.05) relative to the older premenopausal group (n=250). This group also had a non-significant increased rate of lymphovascular invasion and negative progesterone receptor status compared to the older premenopausal group (p&gt; 0.05). Pre-menopausal patients over the age of 35 were twice as likely to have lobular carcinoma as opposed to their younger counterparts. Tumour size, nodal status and axillary node burden was not significantly different between groups. Patients under-35 with breast cancer were more likely to be nulliparous.ConclusionThis data demonstrates that breast cancer in pre-menopausal patients under the age of 35 is associated with adverse clinicopathological features relative to the older pre-menopausal patients. Further studies should be aimed at assessing the prognosis, disease recurrence, disease free survival and distinct genetic profile in age related breast cancer.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3043.
Metabolic Profile (Blood Pressure, Lipids and Body Mass Index) in Relation to Breast Cancer Mortality.
Authors: Emaus A. , Veierød M. , Tretli S. , Finstad S. , Selmer R. , Furberg A. , Bernstein L. , Schlichting E. , Thune I. 
Published: December 2010

Abstract
Background: Metabolic profile (body mass, blood pressure, lipids) may affect biological mechanisms of importance for breast cancer. In the present study we have studied whether these factors are related to breast cancer mortality.Material and Methods: Within the Norwegian Counties Study, a population-based study (1974-2005), we identified 1364 female invasive breast cancer cases.Results: The 1364 cases had a mean age at diagnosis 57.5 years (range 27.1-79.4 years), mean body mass index (BMI) was 24.0 kg/m2, mean systolic blood pressure was 128.1 mmHg, mean diastolic blood pressure 78.6 mmHg, mean serum cholesterol was 6.17 mmol/L and mean HDL-cholesterol was 1.45 mmol/L. A total of 429 cases died during a mean follow-up of 8.2 years. Those with a BMI ≥30 kg/m2 had a 1.45 (CI, 1.07 to 1.95) higher risk of dying during the follow-up than women with a BMI of 18.5–25 kg/m2. Women in the highest tertile of blood pressure had a 43% increase in mortality compared to women in the lowest tertile of blood pressure (HR=1.43, 95% CI, 1.10 to 1.85). Additionally, women in the highest tertile of total cholesterol had a 29% increase in mortality compared to women in the lowest tertile (HR=1.29, 95% CI, 1.01 to 1.65).Conclusion: Our study supports a relationship between total mortality among breast cancer patients and metabolic profile.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3047.
Comparative Validation of the SP6 and MIB1 Antibodies to Ki67 and Their Use in Tissue Microarray (TMA) and Image Analysis for Breast Cancer.
Authors: Zabaglo L. , Zabaglo L. , Salter J. , Salter J. , Anderson H. , Anderson H. , Hills M. , A'Hern R. , Dowsett M. , Dowsett M. 
Published: December 2010

Abstract
Aim: To compare SP6 and MIB1 antibodies against Ki67 for use with visual scoring, image analysis and TMA (tissue microarray) analysis.Background: Immunohistochemical detection of Ki67 has been widely used in assessing the proliferation fraction in breast cancer. Neoadjuvant studies revealed that changes in Ki67 predict benefit from endocrine treatment, and that on-treatment Ki67 measurements are better predictors of long-term outcome than pretreatment levels (Dowsett at al, JNCI 2007; 99:167-170). As a result Ki67 is the primary end-point for some pre-surgical trials. MIB-1 has been the preferred Ki67 antibody for over 10 years. A rabbit monoclonal antibody, SP6, has become available with apparently improved performance, e.g. reduced background non-nuclear staining. The importance of Ki67 led us to conduct a systematic series of studies to validate SP6 in comparison to MIB1.Methods: We used TMAs constructed from (i) 177 archival FFPE blocks of primary or locally recurrent breast tumours from women treated with an aromatase inhibitor (AI) for advanced disease (AI TMAs) and (ii) one set of replicate blocks (200 tumours) from the TransATAC program. The TMAs were of 600µm cores. Three replicate TMAs (A, B, C) were used. Staining was performed using DAKO Autostainer and DAKO REAL Kit Detection System. MIB-1 antibody (DAKO) was used at a dilution of 1:40, whereas 1:100 dilution was used for SP6 antibody (Abcam). Stained sections were examined either visually or using the Ariol image analysis system (Genetix Ltd.).Results: There was a strong correlation between the antibodies in AI TMAs scored manually (n=161, r=0.93, p&lt;0.0001). Coefficient of variation was calculated in all cases with ≥2 available cores. MIB1 showed higher median CV [%] compared with SP6 (43.7 vs. 36.7, respectively) in AI TMAs, but a lower CV in TransATAC TMAs (42.0 vs. 51.4, respectively). In a univariate analysis of manual scores from AI TMAs there was a similar association of Ki67 with time to treatment failure (TTF) with the two antibodies (HR: 1.15; 95% CI: 1.00-1.33; p=0.052 and HR: 1.19; 95% CI: 1.00-1.43; p=0.045 for MIB1 and SP6 respectively). Correlation between manual and image analysis scores was markedly better with the SP6 antibody (r=0.71 and r=0.88 for MIB1 and SP6, respectively).Conclusions: SP6 and MIB1 provide highly comparable measures of Ki67 that predict progression of advanced disease similarly. SP6 is substantially better suited than MIB1 to image analysis, and is now our preferred antibody for future studies.Funded by Breakthrough Breast Cancer and The Mary-Jean Mitchell Green Foundation.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3048.
Outcome of Isolated Sternal Recurrence in Breast Cancer.
Authors: Astrow A. , Desani J. , Sonnenschine M. , Patsiornik Y. , Huang Y. , Klein P. , Citron M. , Reichman B. 
Published: December 2010

Abstract
Introduction: Metastatic breast cancer to sternum is rare and its natural history and prognosis are not fully understood. Metastasis to sternum is considered as stage IV, but may represent local extension from internal mammary nodes. Here we present a case series of 7 patients with metastatic breast cancer to sternum with and without internal mammary node involvement.Method: Seven patients were identified by 5 medical oncologists from New York area with busy breast cancer practices, from 1991 to 2008. Patients chart were reviewed and information regarding age, menopausal status, hormone receptor status, Her2/neu status, initial treatment, time to sternal recurrence and treatment of metastatic disease were obtained.Results: Out of 7 patients with stages I to III at diagnosis, 4 were premenopausal. Two patients had triple negative tumors, 3 were ER/PR positive and 2 were Her2 positive. All patients received loco-regional treatment of the primary site with surgery and/or radiation. Five patients received adjuvant or neoadjuvant chemotherapy. Median time to sternal recurrence was 3 years. Two patients had biopsy confirmed metastasis to internal mammary nodes at relapse. All patients with recurrence received either chemotherapy, radiation or hormonal therapy. One patient received autologous bone marrow transplant after sternal recurrence. All 7 patients are alive, 5 of them in remission and 2 patients with stable disease. Median DFS in 5 patients with CR was 7.8 years.Conclusion: Isolated sternal recurrence with/without internal mammary node involvement is relatively uncommon and is classified as stage IV. On our review of 7 cases, 5 remain in continuous remission at a median of 8 years from recurrence. The other two patients have stable disease. These sternal lesions could possibly represent loco-regional recurrence rather than systemic relapse. Hence, isolated sternal recurrence from breast cancer may need to be stratified separately in studies of stage IV disease.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3054.