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Was zunächst nur als verheißungsvolle Utopie am Zukunftshorizont der Gentechnik aufschien, ist längst dem bioethischen Diskurs entwachsen und konfrontiert uns mit grundlegenden Fragen unseres menschlichen Selbstverständnisses: die Verbesserung und zunehmende Technisierung des Menschen. In diesem Band wird das Thema Enhancement aus sozialphilosophischer und technikphilosophischer Perspektive behandelt. Thomas Zoglauer zeichnet die wesentlichen ethischen Argumentationslinien dieser Debatte nach und setzt sich kritisch mit dem Enhancement unter den Aspekten der Freiheit, sozialen Gerechtigkeit, Chancengleichheit und menschlichen Wohlergehens auseinander. Karsten Weber zeigt wie das Konzept des Cyborgs von der Science-Fiction-Literatur geprägt wurde und als utopisches Leitbild die Medizin- und Neurotechnik beeinflusst hat. Als Folge dieser Entwicklung beginnen sich die Unterschiede zwischen Mensch und Maschine und die damit verbundenen anthropologischen Dichotomien aufzulösen, was auch Konsequenzen für unser Menschenbild und die normative Bewertung des Enhancements hat.

Background In early estrogen receptor (ER)-positive/HER2-negative breast cancer, the decision to administer chemotherapy is largely based on prognostic criteria. The combined molecular/clinical EndoPredict test (EPclin) has been validated to accurately assess prognosis in this population. In this study, the clinical relevance of EPclin in relation to well-established clinical guidelines is assessed. Patients and methods We assigned risk groups to 1702 ER-positive/HER2-negative postmenopausal women from two large phase III trials treated only with endocrine therapy. Prognosis was assigned according to National Comprehensive Cancer Center Network-, German S3-, St Gallen guidelines and the EPclin. Prognostic groups were compared using the Kaplan–Meier survival analysis. Results After 10 years, absolute risk reductions (ARR) between the high- and low-risk groups ranged from 6.9% to 11.2% if assigned according to guidelines. It was at 18.7% for EPclin. EPclin reassigned 58%–61% of women classified as high-/intermediate-risk (according to clinical guidelines) to low risk. Women reclassified to low risk showed a 5% rate of distant metastasis at 10 years. Conclusion The EPclin score is able to predict favorable prognosis in a majority of patients that clinical guidelines would assign to intermediate or high risk. EPclin may reduce the indications for chemotherapy in ER-positive postmenopausal women with a limited number of clinical risk factors.

Gene expression profiles provide important information about the biology of breast tumors and can be used to develop prognostic tests. However, the implementation of quantitative RNA-based testing in routine molecular pathology has not been accomplished, so far. The EndoPredict assay has recently been described as a quantitative RT-PCR-based multigene expression test to identify a subgroup of hormone–receptor-positive tumors that have an excellent prognosis with endocrine therapy only. To transfer this test from bench to bedside, it is essential to evaluate the test–performance in a multicenter setting in different molecular pathology laboratories. In this study, we have evaluated the EndoPredict (EP) assay in seven different molecular pathology laboratories in Germany, Austria, and Switzerland. A set of ten formalin-fixed paraffin-embedded tumors was tested in the different labs, and the variance and accuracy of the EndoPredict assays were determined using predefined reference values. Extraction of a sufficient amount of RNA and generation of a valid EP score was possible for all 70 study samples (100%). The EP scores measured by the individual participants showed an excellent correlation with the reference values, respectively, as reflected by Pearson correlation coefficients ranging from 0.987 to 0.999. The Pearson correlation coefficient of all values compared to the reference value was 0.994. All laboratories determined EP scores for all samples differing not more than 1.0 score units from the pre-defined references. All samples were assigned to the correct EP risk group, resulting in a sensitivity and specificity of 100%, a concordance of 100%, and a kappa of 1.0. Taken together, the EndoPredict test could be successfully implemented in all seven participating laboratories and is feasible for reliable decentralized assessment of gene expression in luminal breast cancer.

Background:Currently, breast cancer during pregnancy (BCP) is not believed to be biologically different from breast cancer unrelated to pregnancy based on limited datasets mainly obtained by immunohistochemistry. However, some groups report that BCP patients have an inferior survival compared to young non-pregnant breast cancer patients. The largest analysis based on the BCP registry by the German Breast Group (GBG) revealed however, no difference between pregnant and non-pregnant breast cancer patients, indicating that treatment rather than biology might be the reason for the inferior survival reported by others. Methods: The BCP study (GBG 29/BIG 03-02) is a multicentre observational study for breast cancer during pregnancy. In tumour tissue collected within this study from pregnant M0 patients we investigated the following genes: AKT1, ATM, BRAF, CBFB, CCND1, CDH1, CDKN2A, CTCF, EGFR, ERBB2, ESR1, FGFR2, GATA3, KRAS, MAP2K4, MAP3K1, MDM2, MED12, MYC, PIK3CA, PIK3R1, PTEN, RB1, RUNX1, and TP53 by massive parallel sequencing (MPS). This included patients with all molecular subtypes: HR+/-, HER2+/-. Sequencing was done on an IonTorrent Proton using a custom designed Breast Cancer Panel (BCPv2). This panel comprises 236 amplicons split into two primer pools and covers hotspot regions of 138 exons of the 25 genes. To test the hypothesis that breast cancer diagnosed during pregnancy is biologically not different from breast cancer diagnosed in young non-pregnant women, we compared the molecular profiles obtained, with genetic data from M0 patients not known to be pregnant from TCGA with age Results: Material from 141 patients from the BCP study was available from which ultimately 109 fully evaluable MPS datasets could be obtained. In the TCGA data set 114 breast cancer patients Exact matching by variables age, HR, HER2 and grade yielded 40 patients from both datasets. In these subcohorts, still divergent mutational rates for TP53 and PIK3CA between pregnant and non-pregnant women were noted, however, the differences failed to reach statistical significance. Conclusions: Overall the mutational landscapes do not seem to be overtly different between pregnant patients and no-pregnant controls, although slight imbalances in mutational rates occurred, which might be partly explained by a selection bias and a small sample size after matching. Further comparisons using other datasets, looking into survival and regarding copy number variation are currently conducted. This research is been funded by the German Cancer Consortium-DKTK and the BANSS Foundation. Citation Format: Loibl S, Pfarr N, Weber K, Neunhöffer T, Villegas S, Stenzinger A, Furlanetto J, Aktas B, Budczies J, Marmé F, Kahmann L, Denkert C, Weichert W. Comparison of the mutational landscape of breast cancer during pregnancy and non-pregnant controls [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-03-09.

Background: The EndoPredict (EP) score is a multigene classifier to predict the likelihood of distant recurrence in ER-positive, HER2−negative breast cancer patients treated with adjuvant endocrine therapy. Two large randomized phase III trials involving endocrine therapy only (n > 1700) demonstrated additional prognostic information of the EP score independent from clinicopathological parameters by classifying 49% as low risk. However, the predictive role of the EP is not clear. Therefore, we examined whether the EP Score also predicts sensitivity towards neoadjuvant chemotherapy in ER-positive, HER2−negative breast cancer patients. Methods: Four publicly available gene expression data sets (Affymetrix HG-U133A) were retrieved from the gene expression omnibus (GEO) data repository. All analyzed breast cancer patients were treated with anthracycline or taxane/anthracycline-based neoadjuvant chemotherapy. Microarray cel files were MAS5 normalized with a global scaling procedure and a target intensity of 500. The analysis was restricted to ER-positive, HER2−negative breast cancer patients according to pre-specified cut-off levels for the respective ESR1/ERBB2 Affymetrix probesets. The EP score was calculated and patients were classified as having low or high risk according to the pre-specified validated cut-off value. Pathological complete response (pCR) — defined as no residual invasive cancer in the breast or lymph nodes — was used as the primary endpoint for the assessment of treatment response. Results: The EP Score was examined in 221 ER-positive, HER2−negative breast cancer patients treated with neoadjuvant therapy. Among the 221 patients, 61 tumors (27.6%) were classified as EP-low-risk, whereas 160 tumors (72.4%) were EP-high-risk. Only one of the EP-low-risk tumors achieved a pCR after neoadjuvant therapy, whereas 24 of the 25 pCR events were classified as EP high risk. The sensitivity of the EP score was 96% and the negative predictive value 98% with an area under the receiver operating characteristic curve of 0.73. Conclusions: The EP Score is a predictor of chemosensitivity in the neoadjuvant setting. The test correctly identified all but one of the patients achieving a pCR suggesting that the benefit of cytotoxic chemotherapy is limited to the EP high risk group. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-06-26.

The development of optimized therapy strategies against malignant tumors is critically dependent on the assessment of tissue-based biomarkers in routine diagnostic tissue samples. We investigated a novel, fully automated, and xylene-free method for RNA isolation and biomarker determination using formalin-fixed paraffin-embedded (FFPE) tissue. The aim was to show that this approach is feasible and gives results that are comparable to the current gold standards. Expression of the breast cancer biomarkers ESR1, PGR, and HER2 was measured in a total of 501 FFPE tissue samples from 167 breast carcinomas, which had been stored for up to 21 years. Total RNA was extracted from tissue sections and biomarker expression was measured by kinetic RT-PCR (RT-kPCR). The results of the new method were compared with immunohistochemistry as the current gold standard.RNA was successfully isolated from all samples, with a mean yield of 1.4 μg/sample and fragment lengths of at least 150 bp in 99% of samples. RT-kPCR analysis of ESR1, PGR, and HER2 was possible in all samples. Comparing RT-kPCR results with standard IHC, we found a good concordance for ESR1 (agreement: 98.4%), PGR (84.4%), and HER2 (89.8%). We observed a low section-to-section variability of kPCR results for all 3 biomarkers (root of mean squared errors: 0.2 to 0.5 Ct values). The new approach is a reliable high-throughput instrument for standardized testing of biomarkers in clinical routine and for research studies on archived FFPE material up to 21 years old. For the assessment of ESR1, PGR, and HER2 the results are comparable to the current gold-standard.

Background: Molecular tests predicting outcome of breast cancer patients may be useful for treatment decisions in addition to standard clinicopathologic features. Methods: Using human genome HG-U133A array and qRT-PCR datasets, we developed and validated a gene-expression signature predicting the likelihood of distant recurrence in postmenopausal, early-stage breast cancer patients with estrogen receptor-positive, HER2-negative tumors treated with adjuvant endocrine therapy. RNA levels assessed by qRT-PCR in formalin-fixed paraffin-embedded tumor specimens were used to calculate a risk score (T5) and to determine a risk group (low or high) for each patient. The prospectively defined T5 risk score was then validated independently in patients from two large randomized phase III trials. Distant recurrence-free survival and overall survival were analyzed with Cox models adjusted for clinicopathological factors. The primary endpoint was time to distant recurrence. Results: In a training set of 964 tumors, we identified a gene-expression signature consisting of three proliferation-related genes (BIRC5, UBE2C, DHCR7), five estrogen-regulated genes (RBBP8, IL6ST, AZGP1, MGP, STC2), and three reference genes (CALM2, OAZ1, RPL37A). For the validation, RNA analysis was possible in 1702 of 1725 (99%) tumors of both validation sets. Women were classified as having low risk (n=832; 49%) or high risk (n=870; 51%) by the T5 risk score. The T5 risk score provided prognostic information independent from clinicopathologic risk as estimated by Adjuvant!Online or Ki67 labeling index. Patients with a higher T5 risk score had a significantly shorter time to distant recurrence (adjusted hazard ratio, 1.24; 95% confidence interval [CI], 1.15 to 1.33; P Conclusions: Using formalin-fixed paraffin-embedded tumor specimens, the multigene T5 risk score provides prognostic information independent of Adjuvant!Online or Ki67 labeling index. By combining the T5 risk score with clinicopathological risk, we were able to accurately identify breast cancer patients with low risk or high risk for distant recurrence. Using this new easy-to-use multigene tool in clinical practice will assist in optimizing adjuvant therapy by reducing both undertreatment and overtreatment and thus improves outcome and quality of life of patients with early-stage breast cancer. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-07.

Within the information ethics community one can observe a mainstream discussion including some fundamental presuppositions which appear to be something like dogmas. The most important of these dogmas seems to be that we must create a new kind of intercultural information ethics. It is often argued that (comparative) studies have shown that different cultures, according to culturally determined norms and values, react in different ways to the impacts of ICT; it is stressed that an intercultural information ethics must take these cultural particularities into account. But in the paper at hand it shall be argued that taking cultural differences into consideration does not create a necessity to invent a new intercultural information ethics. On the contrary it shall be claimed that we already know several intercultural ethics which only have to be applied to ICT and its impact to societies.

Background: Targeted next-generation sequencing (NGS) enables investigation of key molecular events in breast cancer (BC) and driver genes. In this study we evaluated the relevance of mutations in 15 cancer genes and copy number amplifications in 8 cancer genes for response to neoadjuvant therapy in the GeparSepto cohort. The pCR rate was significantly higher in patients treated with nab-paclitaxel (nP) instead of paclitaxel (P). Methods: A total of 851 pretherapeutic formalin-fixed paraffin embedded (FFPE) core biopsies including luminal/HER2- (n=397), HER2+ (n=295) and TNBC (n=159) tumors from the neoadjuvant GeparSepto trial were analysed by targeted NGS. We used a panel of 21 genes including 15 genes selected for mutation analysis (AKT1, ATM, CCND1, CDH1, EGFR, ERBB2, FBXW7, FGFR2, HRAS, KRAS, NRAS, PIK3CA, PTEN, SF3B1, TP53) and 8 genes selected for amplifications (CCND1, ERBB2, FGFR1, PAK1, PIK3CA, TOP2A, TP53, ZNF703). Results: The most prevalent mutations were in TP53 (38.4%), ATM (27.7%) and PIK3CA (21.5%) genes; the amplification frequencies were TOP2a (34.9%), ERBB2 (30.6%), ZNF703 (30.1%), PIK3CA (24.1%), TP53 (21.9%), CCND1 (17.7%), PAK1 (14.9%) and FGFR1 (12.6%). Amplification of ERBB2 was observed in 84.7% of HER2+ BC, but only in 1.5% of luminal/HER2- BC and 2.5% of TNBC (p Conclusion: NGS sequencing of FFPE samples from clinical trials is feasible, detects mutations and copy number alterations, and reveals high molecular heterogeneity indifferent BC types. Our results points to PIK3CA as a major mechanism of therapy resistance in BC, which might also be relevant for response to nP vs standard P. In general, NGS holds promise to identify markers of therapy resistance as a basis for individualized and new molecular-targeted BC therapies. Citation Format: Sibylle Loibl, Denise Treue, Jan Budczies, Karsten Weber, Albrecht Stenzinger, Wolfgang D. Schmitt, Wilko Weichert, Paul Jank, Jenny Furlanetto, Frederick Klauschen, Thomas Karn, Nicole Pfarr, Gunter von Minckwitz, Annika Lehmann, Christian Jackisch, Christine Sers, Andreas Schneeweiss, Peter A. Fasching, Christian Schem, Michael Hummel, Marion van Mackelenbergh, Valentina Nekljudova, Michael Untch, Carsten Denkert. Mutational diversity and therapy response in breast cancer-a sequencing analysis in the neoadjuvant GeparSepto trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-027.

527Background: Immunogenic infiltrate in breast cancer (BC) may influence the prognosis and response to systemic therapies. The association and prognostic role of tumor infiltrating lymphocytes (TI...

574Background: Different mutational processes act over the evolutionary history of a malignant tumor, driven by e.g. abnormal DNA editing, mutagens or age-related DNA alterations. Many of these pro...

A difference in pressure is generated between the two sides of a filter medium (1) so that the liquid (2) charged with biopolymers (3), for instance xanthan, that is fed through the inlet (5) goes through the filter medium (1), wherein the biopolymers (3) are retained by the filter medium (1). As opposed to crossflow filtration, the main direction of movement (4) of the liquid (2) is determined by the difference in transmembrane pressure. A cathode (7) is arranged under the filter membrane (1). A membrane serving as anode (8) is arranged on the opposite side of the process chamber (9). An electrical field is built up between the electrodes (7, 8). Due to the fact that the biopolymer components (3) carry a negative surface charge, a force moving in the direction of the anode (8), and, hence, against the main direction of movement (4) of the liquid (2), impinges upon said components in the electrical field (8), whereby the concentration of biopolymers is reduced in the surroundings of the filter medium (1) and filtration speed is increased. A surprising, additional effect is that the electrical field leads to reinforced coagulation tendency of the biopolymers (3) which further favors filtration by the formation of agglomerates.

Simulation in the Social Sciences. Computer simulation—hereafter just called ‘simulation’— more and more is getting an important tool in scientific research and development. Simulations provide powerful means for quite different scientific disciplines, for instance for cosmology as well as for economics, and it seems that they can help to extend the borderline of science. However, from a methodological point of view, besides their benefits one can identify several theoretical problems which can occur in the process of scientific research. Some of these problems shall be discussed and consequences of these problems for the use of simulations shall be outlined.

After a brief introduction of definitions and causes of the digital divide, particularly with regard to developing countries, the so-called “Simputer” and “One Laptop per Child” projects, which were designed to close the digital divide in developing countries, will be presented. It shall be argued that both projects are flawed by technological determinism and false assumptions about the impact of technology on social problems. As a conclusion it shall be predicted that the “One Laptop per Child” project is very likely to fail as the “Simputer” project already has failed.

Background: Mutations in BRCA1 and BRCA2 influence the molecular pathogenesis of breast cancer. However, little is known about the association between mutations, response to therapy, and prognosis. We therefore analysed these associations in triple negative breast cancer (TNBC) patients in the neoadjuvant GeparQuinto Study. Methods: The GeparQuinto study recruited 1956 patients with HER2 negative disease including a prespecified group of 671 TNBC patients with untreated breast cancer. Patients were randomized to receive four cycles EC (90/600 mg/m2; q3w) followed by four cycles docetaxel (100 mg/m2; q3w), with or without bevacizumab (15 mg/kg). Here we present the analysis for both randomization arms combined. Sufficient blood was available of 482 TNBC patients. BRCA1 and BRCA2 genotyping was successful in 469 patients with available germline DNA and was conducted by SureSelect custom capture and sequencing on HiSeq 2500. Mutation status was correlated with pathological complete response rates (pCR) and disease free survival (DFS). Results: A total of 74 (15.8%) mutations in BRCA1 (n=61) and BRCA2 (n=13) were detected after initial sequencing. A pCR (ypT0/ypN0) was observed in 50% (n=37) of mutation carriers but only 31.1% (n=123) of patients without mutations (p=0.002). Similar results were observed for pCR (pT0is/pN0) (52.7% vs. 36.5%; p=0.010). pCR (ypT0/ypN0) was predictive of disease free survival (DFS) in all patients (Hazard Ratio, HR=0.23; 95%CI: 0.15-0.37; p Conclusion: TNBC Patients with BRCA mutations showed a higher frequency of pCR than patients without BRCA mutations after treatment with epirubicin, cyclophosphamide and docetaxel (+/ bevacizumab), suggesting that BRCA mutations may influence pCR in response to treatment regimens that do not include platin chemotherapy. pCR as a surrogate marker for DFS was also confirmed in patients without BRCA mutations. In addition, the effect of pCR on prognosis seemed to be smaller among the mutation carriers, although the number of mutation carriers was too low to test for differences between mutation carriers and wildtype patients. The project has partly been funded within NIH-NIGMS U19 GM61388 and the Breast Cancer Research Foundation. Citation Format: Fasching PA, Loibl S, Eidtmann H, Tesch H, Untch M, Hilfrich J, Schem C, Rezai M, Gerber B, Costa SD, Blohmer JU, Fehm TN, Huober J, Liedtke C, Müller V, Nekljudova V, Weber K, Rack B, Rübner M, Wang L, Ingle JN, Weinshilboum RM, von Minckwitz G, Couch F. BRCA mutations, therapy response and prognosis in the neoadjuvant GeparQuinto study. [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 S5-06.

This paper presents a possibility of calculating the zeta potentiel of a filter cake from permeation experiments by considering the influence of an electric field.

The need to dehydrate finely dispersed products is increasing worldwide. The electrofiltration potential increases with the particle surface area. Therefore the combination of mechanical and electrical filtration seems to be an effective method to enhance filtration kinetics. The attemps at pressure electrofiltration attempted in this work showed, that the residual moisture could only be lowered slightly by the electrical field, which itself is due to the electrolytic gas generated.

AimThis study compared the perfomance of the RNA-based EndoPredict multigene test on core biopsies and surgical breast cancer specimens and analysed the influence of biopsy-induced tissue injuries on the test result.Methods80 formalin-fixed paraffin-embedded samples comprising paired biopsies and surgical specimens from 40 ER-positive, HER2-negative patients were evaluated. Total RNA was extracted and the EndoPredict score was determined.ResultsRNA yield was considerably lower in core biopsies, but sufficient to measure the assay in all samples. The EndoPredict score was highly correlated between paired samples (Pearson r=0.92), with an excellent concordance of classification into a low or high risk of metastasis (overall agreement 95%).ConclusionsThe measurements are comparable between core biopsies and surgical sections, which suggest that the EndoPredict assay can be performed on core biopsy tissue. Inflammatory changes induced by presurgical biopsies had no significant effect on the RNA-based risk assessment in surgical specimens.

The requirement to dewater finely dispersed products is rising world-wide. Because the flow resistance increases with decreasing particle size, the mechanical dewatering of fine particle suspensions is time-consuming. The electrofiltration potential increases with the particle surface area. Therefore the combination of mechanical and electrical filtration seems to be an effective method to enhance the filtration kinetics. Experiments at the Institute of Mechanical Process Engineering and Mechanics (MVM) at the University of Karlsruhe (TH) showed that this combination results in an acceleration of the filtration kinetics. Thus the filtration time was less than half compared to traditional pressure filtration. If an electric field is applied in addition to pressure dewatering, four additional effects occur. On the one hand, the electrokinetic effects of electroosmosis and electrophoresis benefit filtration. The electrophoresis decreases the migration velocity of the particles. The electroosmosis moves the surrounding diffusive layer of the particles and promotes the filtration flow. On the other hand, electrolysis and a decrease in thermal viscosity occur. As a result of the applied electric field, the fluid is electrolytically decomposed and electrolytic gas is generated. This gas displaces water but also increases the electric resistance between the electrodes. The electric resistance of the bulk converts electrical energy into thermal energy, resulting in a temperature rise of the suspension or filter cake. An increasing temperature causes a lower viscosity and easier dewatering. These single effects and their influence on the process have to be known in order to succeed in industrial implementation of the process. The dewatering effect of the generated electrolytic gas can be calculated by a continuity balance. The change in viscosity can be eliminated by knowledge of the temperature. Based on the root equation of cake building filtration, Yukawa developed an equation for pressure electrofiltration. The electrokinetic effects can be separated using this equation. The electroosmotic pressure and the electrophoretic coefficient can then be calculated if the filter media and bulk resistance are known. Experiments on a specially constructed pressure/electro filter showed that the acceleration of the filtration kinetics is mainly caused by electrophoresis. Electroosmosis only has a little effect. The bulk resistance, which mainly influences the filtration kinetics, will be abated by the electrophoretically reduced particle velocity.

Technology penetrates into all areas of our everyday and individual life and changes it in a considerable speed. This applies particularly to developments of information and communication technology since this technology shows its effects not only at our workplaces but transforms and sometimes determines the social behavior of people. Unfortunately, development and use of technology certainly doesn't go hand into hand with the acceptance of responsibility for consequences of effects of developing and using technology. Instead, the opposite behavior is quite common. If this process of the rejection of responsibility shall be stopped, the sensibility of developers and users of technology for consequences of their own behavior have to be aroused and strengthened. In the following text at first I will describe some reasons to formulate ethical guidelines. After this, with the example of the ethical guidelines of the German Gesellschaft für Informatik e. V. (GI), I will discuss, whether such ethical guidelines are ethical in the strict sense of the word and whether they actually can be a contribution to accomplish the striven aim of assignment of responsibility for the results of developing and using technolog

Introduction: EndoPredict (EP) is an RNA-based multigene test that predicts the likelihood of distant recurrence in patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC) who are being treated with adjuvant endocrine therapy. Herein we report the prospective-retrospective clinical validation of EP in the node-positive, chemotherapy-treated, ER+/HER2- BC patients in the GEICAM 9906 trial. Methods: The patients (N = 1,246) were treated either with six cycles of fluorouracil, epirubicin and cyclophosphamide (FEC) or with four cycles of FEC followed by eight weekly courses of paclitaxel (FEC-P), as well as with endocrine therapy if they had hormone receptor-positive disease. The patients were assigned to EP risk categories (low or high) according to prespecified cutoff levels. The primary endpoint in the clinical validation of EP was distant metastasis-free survival (MFS). Metastasis rates were estimated using the Kaplan-Meier method, and multivariate analysis was performed using Cox regression. Results: The molecular EP score and the combined molecular and clinical EPclin score were successfully determined in 555 ER+/HER2- tumors from the 800 available samples in the GEICAM 9906 trial. On the basis of the EP, 25% of patients (n = 141) were classified as low risk. MFS was 93% in the low-risk group and 70% in the high-risk group (absolute risk reduction = 23%, hazard ratio (HR) = 4.8, 95% confidence interval (CI) = 2.5 to 9.5; P < 0.0001). Multivariate analysis showed that, in this ER+/HER2- cohort, EP results are an independent prognostic parameter after adjustment for age, grade, lymph node status, tumor size, treatment arm, ER and progesterone receptor (PR) status and proliferation index (Ki67). Using the predefined EPclin score, 13% of patients (n = 74) were assigned to the low-risk group, who had excellent outcomes and no distant recurrence events (absolute risk reduction vs high-risk group = 28%; P < 0.0001). Furthermore, EP was prognostic in premenopausal patients (HR = 6.7, 95% CI = 2.4 to 18.3; P = 0.0002) and postmenopausal patients (HR = 3.3, 95% CI = 1.3 to 8.5; P = 0.0109). There were no statistically significant differences in MFS between treatment arms (FEC vs FEC-P) in either the high-or low-risk groups. The interaction test results between the chemotherapy arm and the EP score were not significant. Conclusions: EP is an independent prognostic parameter in node-positive, ER+/HER2- BC patients treated with adjuvant chemotherapy followed by hormone therapy. EP did not predict a greater efficacy of FEC-P compared to FEC alone.

In den zuruckliegenden Jahren sind zahlreiche prognostische und pradiktive Multiparameteralgorithmen, basierend auf der Analyse von messenger-Ribonukleinsaure (mRNA), veroffentlich worden. Viele dieser Algorithmen erfordern RNA, die aus Frischgewebe bzw. frisch eingefrorenem Gewebe isoliert werden muss. Fur die klinische Routine ist formalinfixiertes Gewebe jedoch ein weitaus geeigneteres Ausgangsmaterial. Siemens Healthcare Diagnostics entwickelt deswegen eine robotergestutzte, vollautomatische Methode fur die Extraktion von mRNA und Desoxyribonukleinsaure (DNA) aus formalinfixiertem sowie paraffineingebettetem Gewebe fur das Pathologielabor. Die Methode soll erstmals als Teil eines Prognosetests fur das Metastase- und Todesrisiko von Patientinnen mit nodal-negativem Brustkrebs Anwendung finden, der sich ebenfalls bei Siemens Healthcare Diagnostics in der Produktentwicklung befindet.

In his remarkable article “Imposing Genetic Diversity” (2015) the author Robert Sparrow, by using several thought experiments to support his arguments, claims that with regard to human beings it is...

This paper shall give a review of some recently published and some older books, which were published as second or third edition, on Information Ethics and Internet related topics: - Brennan, Linda L. & Victoria E. Johnson (eds.): Social, Ethical, and Policy Implications of Information Technology. Hershey, PA: Information Science Publishing, 2004. – 304 pages, paperback, $59.95 - Capurro, Rafael: Ethik im Netz. Wiesbaden: Franz Steiner, 2003. 278 pages, paperback, €26.00 - Cavalier, Robert J. (ed.): The impact of the Internet on our moral lives. Albany, NY: State University of New York Press, 2005. – 249 pages, paperback, $26.95 - Johnson, Deborah G.: Computer Ethics. Upper Saddle River, NJ: Prentice Hall, third edition, 2001. – 240 pages, paperback, $40.67 - Kuhlen, Rainer: Informationsethik. Umgang mit Wissen und Informationen in elektronischen Räumen. Konstanz: UVK (UTB), 2004. – 444 pages, paperback, €24.95 - Nyíri, Kristóf: Vernetztes Wissen. Philosophie im Zeitalter des Internets. Wien: Passagen Verlag, 2004. – 179 pages, paperback, €19.95 - Spinello, Richard A.: Case Studies in Information Technology Ethics. Upper Saddle River, NJ: Prentice Hall, second edition, 2003. – 252 pages, paperback, $54.67 - Spinello, Richard A. & Herman T. Tavani (eds.): Readings in Cyberethics. Sudbury, NJ: Jones and Bartlett Publishers, second edition, 2004. – 697 pages, paperback, $54.95 - Tavani, Herman T.: Ethics & Technology. Ethical Issues in an Age of Information and Communication Technology. Hoboken, NJ: John Wiley and Sons, 2004. 344 pages, paperback, $53.95

Given that people living in western-style democracies actually have almost unrestricted and unlimited access to information it could be asked whether this access really can fulfill all the promises and hopes often stated with regard to the so-called information age: people will be much better informed, have much greater knowledge, will have much more opportunities to take part in political decision-making processes, and for the first time in history really can enjoy freedom of expression and freedom to inform themselves. And there are even more promises: the power of governments and state authorities as well as of private media companies will be pushed back, private media companies’ role as gatekeepers will be obsolete and therefore they would not be able to set the political agenda any longer. Besides those more or less political issues there are a lot of other hopes concerning the Internet and its impact to society, mostly economic expectations. In the my paper evidence will be presented that most if not all of the above mentioned expectations – particularly those concerning better knowledge and political participation and deliberation – were in vain. It will be claimed that although people in western-style democracies have almost all information at their fingertips they are not really better informed, they do not take part in political decision-making processes in larger numbers, and they still rather consume information than producing it. Additionally, many people tend to take into account only information that confirms their previous knowledge and their already existing prejudice. Therefore, based on the analysis of empirical research, itI shall be claimed that one – and maybe the most eminent – effect of ubiquitous access to information is the fragmentation of knowledge and therefore of society. The hope that the global dissemination of information and communication technology itself could increase social cohesion actually was badly disappointed.