Ordnungstheorie – Ordnungspolitik: Was ist Neoliberalismus?

Der Begriff Neoliberalismus ist angesichts der Finanzkrise in Misskredit geraten. Aber was bedeutet eigentlich Neoliberalismus? Viktor J. Vanberg, Walter Eucken Institut, Freiburg, definiert Ordnungstheorie als das wirtschafts- und rechtswissenschaftliche Forschungsprogramm der Freiburger Schule und ihr verwandter Denkansätze, das das Augenmerk auf die Steuerungswirkungen richtet, die die rechtlich-institutionellen Rah-menbedingungen auf die in ihnen stattfindenden wirtschaftlichen Prozessabläufe aus-üben. Ordnungspolitik ist der angewandte Zweig dieses Forschungsprogramms. Die ordoliberale Ordnungsökonomik richte ihr Forschungsinteresse auf die Frage, wie die institutionellen Rahmenbedingungen, unter denen Individuen agieren und kooperieren, in einer Weise gestaltet werden können, die ihnen bestmögliche Aussichten biete, in wechselseitig kompatibler Freiheit ihre eigenen Zwecke zu verfolgen. Für Wernhard Möschel, Universität Tübingen, ist eine marktwirtschaftliche Ordnung nicht denkbar ohne inhaltliche Normierungen. Auch bei einem neoliberalen Ansatz bleibe Raum für ergänzende und für korrigierende Politiken. Heiner Flassbeck, UNCTAD, und Friederi-ke Spiecker sehen dagegen den Neoliberalismus »mit seiner undifferenzierten Vorstel-lung, den Staat auf ein ordnungspolitisches Minimum zur Organisation des freien Wett-bewerbs auf freien Märkten zu reduzieren«, als gescheitert an. Der Wirtschaftspolitik sollte ein klares Primat gegenüber spekulationsanfälligen Märkten eingeräumt werden. Peter Hampe, Technische Universität Dresden und Münchner Hochschule für Politik, betrachtet die Entstehungsgeschichte des Neoliberalismus und erläutert die Differenz zwischen Neo- und Paleoliberalismus. Hans-Werner Sinn erklärt die Position des Neo-liberalismus anhand eines Fußballspiels.Wirtschaftsliberalismus, Ordnungstheorie, Ordnungspolitik

Der pathologische Exportboom: These und Stellungnahmen

Die deutsche Volkswirtschaft gibt Rätsel auf: Einerseits ist Deutschland Export-(Vize-)Weltmeister, andererseits leidet es unter einer anhaltenden Wachstums- und Beschäftigungsschwäche. Ist das Exportwachstum Ausdruck ungebrochener internationaler Wettbewerbsfähigkeit und die Wachstums- und Beschäftigungsschwäche nur ein konjunkturelles Problem, das sich einem Mangel an privater Binnennachfrage verdankt. Oder deutet das Nebeneinander von Wirtschaftskrise und Exportboom auf ein Standortproblem Deutschlands im Allgemeinen und ein Lohnproblem im Besonderen hin

Der pathologische Exportboom These und Stellungnahmen

Die deutsche Volkswirtschaft gibt Rätsel auf: Einerseits ist Deutschland Export-(Vize-)Weltmeister, andererseits leidet es unter einer anhaltenden Wachstums- und Beschäftigungsschwäche. Ist das Exportwachstum Ausdruck ungebrochener internationaler Wettbewerbsfähigkeit und die Wachstums- und Beschäftigungsschwäche nur ein konjunkturelles Problem, das sich einem Mangel an privater Binnennachfrage verdankt. Oder deutet das Nebeneinander von Wirtschaftskrise und Exportboom auf ein Standortproblem Deutschlands im Allgemeinen und ein Lohnproblem im Besonderen hin?Export, Lohn, Arbeitskosten, Beschäftigung, Wertschöpfung, Arbeitslosigkeit, Deutschland

Clinicopathologic and molecular analysis of embryonal rhabdomyosarcoma of the genitourinary tract: evidence for a distinct DICER1-associated subgroup.

Embryonal rhabdomyosarcoma (ERMS) of the uterus has recently been shown to frequently harbor DICER1 mutations. Interestingly, only rare cases of extrauterine DICER1-associated ERMS, mostly located in the genitourinary tract, have been reported to date. Our goal was to study clinicopathologic and molecular profiles of DICER1-mutant (DICER1-mut) and DICER1-wild type (DICER1-wt) ERMS in a cohort of genitourinary tumors. We collected a cohort of 17 ERMS including nine uterine (four uterine corpus and five cervix), one vaginal, and seven urinary tract tumors. DNA sequencing revealed mutations of DICER1 in 9/9 uterine ERMS. All other ERMS of our cohort were DICER1-wt. The median age at diagnosis of patients with DICER1-mut and DICER1-wt ERMS was 36 years and 5 years, respectively. Limited follow-up data (available for 15/17 patients) suggested that DICER1-mut ERMS might show a less aggressive clinical course than DICER1-wt ERMS. Histological features only observed in DICER1-mut ERMS were cartilaginous nodules (6/9 DICER1-mut ERMS), in one case accompanied by foci of ossification. Recurrent mutations identified in both DICER1-mut and DICER1-wt ERMS affected KRAS, NRAS, and TP53. Copy number analysis revealed similar structural variations with frequent gains on chromosomes 2, 3, and 8, independent of DICER1 mutation status. Unsupervised hierarchical clustering of array-based whole-genome DNA methylation data of our study cohort together with an extended methylation data set including different RMS subtypes from genitourinary and extra-genitourinary locations (n = 102), revealed a distinct cluster for DICER1-mut ERMS. Such tumors clearly segregated from the clusters of DICER1-wt ERMS, alveolar RMS, and MYOD1-mutant spindle cell and sclerosing RMS. Only one tumor, previously diagnosed as ERMS arising in the maxilla of a 6-year-old boy clustered with DICER1-mut ERMS of the uterus. Subsequent sequencing analysis identified two DICER1 mutations in the latter case. Our results suggest that DICER1-mut ERMS might qualify as a distinct subtype in future classifications of RMS

Obesity as risk factor for subtypes of breast cancer: results from a prospective cohort study

Background: Earlier epidemiological studies indicate that associations between obesity and breast cancer risk may not only depend on menopausal status and use of exogenous hormones, but might also differ by tumor subtype. Here, we evaluated whether obesity is differentially associated with the risk of breast tumor subtypes, as defined by 6 immunohistochemical markers (ER, PR, HER2, Ki67, Bcl-2 and p53, separately and combined), in the prospective EPIC-Germany Study (n = 27,012). Methods: Formalin-fixed and paraffin-embedded (FFPE) tumor tissues of 657 incident breast cancer cases were used for histopathological analyses. Associations between BMI and breast cancer risk across subtypes were evaluated by multivariable Cox regression models stratified by menopausal status and hormone therapy (HT) use. Results: Among postmenopausal non-users of HT, higher BMI was significantly associated with an increased risk of less aggressive, i.e. ER+, PR+, HER2-, Ki67low, Bcl-2+ and p53- tumors (HR per 5 kg/m2: 1.44 [1.10, 1.90], p = 0.009), but not with risk of more aggressive tumor subtypes. Among postmenopausal users of HT, BMI was significantly inversely associated with less aggressive tumors (HR per 5 kg/m2: 0.68 [0.50, 0.94], p = 0.018). Finally, among pre- and perimenopausal women, Cox regression models did not reveal significant linear associations between BMI and risk of any tumor subtype, although analyses by BMI tertiles showed a significantly lower risk of less aggressive tumors for women in the highest tertile (HR: 0.55 [0.33, 0.93]). Conclusion: Overall, our results suggest that obesity is related to risk of breast tumors with lower aggressiveness, a finding that requires replication in larger-scale analyses of pooled prospective data

Prognosis of breast cancer molecular subtypes in routine clinical care: A large prospective cohort study

Background: In Germany, most breast cancer patients are treated in specialized breast cancer units (BCU), which are certified, and routinely monitored. Herein, we evaluate up-to-date oncological outcome of breast cancer (BC) molecular subtypes in routine clinical care of a specialized BCU. Methods: The study was a prospectively single-center cohort study of 4102 female cases with primary, unilateral, non-metastatic breast cancer treated between 01 January 2003 and 31 December 2012. The five routinely used molecular subtypes (Luminal A-like, Luminal B/HER2 negative-like, Luminal B/HER2 positive-like, HER2-type, Triple negative) were analyzed. The median follow-up time of the whole cohort was 55 months. We calculated estimates for local control rate (LCR), disease-free survival (DFS), distant disease-free survival (DDFS), overall survival (OS), and relative overall survival (ROS). Results: Luminal A-like tumors were the most frequent (44.7%) and showed the best outcome with LCR of 99.1% (95% CI 98.5; 99.7), OS of 95.1% (95% CI 93.7; 96.5), and ROS of 100.0% (95% CI 98.5; 101.5). Triple negative tumors (12.3%) presented the poorest outcome with LCR of 89.6% (95% CI 85.8; 93.4), OS of 78.5% (95% CI 73.8; 83.3), and ROS of 80.1% (95% CI 73.8; 83.2). Conclusions: Patients with a favorable subtype can expect an OS above 95% and an LCR of almost 100% over 5 years. On the other hand the outcome of patients with HER2 and Triple negative subtypes remains poor, thus necessitating more intensified research and care

AGO Recommendations for the Diagnosis and Treatment of Patients with Locally Advanced and Metastatic Breast Cancer: Update 2022

The Breast Committee of the Arbeitsgemeinschaft Gynakologische Onkologie (German Gynecological Oncology Group, AGO) presents the 2022 update of the evidence-based recommendations for the diagnosis and treatment of patients with locally advanced and metastatic breast cancer

HER2 and ESR1 mRNA expression levels and response to neoadjuvant trastuzumab plus chemotherapy in patients with primary breast cancer

Introduction: Recent data suggest that benefit from trastuzumab and chemotherapy might be related to expression of HER2 and estrogen receptor (ESR1). Therefore, we investigated HER2 and ESR1 mRNA levels in core biopsies of HER2-positive breast carcinomas from patients treated within the neoadjuvant GeparQuattro trial. Methods: HER2 levels were centrally analyzed by immunohistochemistry (IHC), silver in-situ hybridization (SISH) and qRT-PCR in 217 pretherapeutic formalin-fixed, paraffin-embedded (FFPE) core biopsies. All tumors had been HER2-positive by local pathology and had been treated with neoadjuvant trastuzumab/ chemotherapy in GeparQuattro. Results: Only 73% of the tumors (158 of 217) were centrally HER2-positive (cHER2-positive) by IHC/SISH, with cHER2-positive tumors showing a significantly higher pCR rate (46.8% vs. 20.3%, p<0.0005). HER2 status by qRT-PCR showed a concordance of 88.5% with the central IHC/SISH status, with a low pCR rate in those tumors that were HER2-negative by mRNA analysis (21.1% vs. 49.6%, p<0.0005). The level of HER2 mRNA expression was linked to response rate in ESR1-positive tumors, but not in ESR1-negative tumors. HER2 mRNA expression was significantly associated with pCR in the HER2-positive/ESR1-positive tumors (p=0.004), but not in HER2-positive/ESR1-negative tumors. Conclusions: Only patients with cHER2-positive tumors - irrespective of the method used - have an increased pCR rate with trastuzumab plus chemotherapy. In patients with cHER2-negative tumors the pCR rate is comparable to the pCR rate in the non-trastuzumab treated HER-negative population. Response to trastuzumab is correlated to HER2 mRNA levels only in ESR1-positive tumors. This study adds further evidence to the different biology of both subsets within the HER2-positive group

Clinical response after two cycles compared to HER2, Ki-67, p53, and bcl-2 in independently predicting a pathological complete response after preoperative chemotherapy in patients with operable carcinoma of the breast

Introduction To investigate the predictive value of clinical and biological markers for a pathological complete remission after a preoperative dose-dense regimen of doxorubicin and docetaxel, with or without tamoxifen, in primary operable breast cancer. Methods Patients with a histologically confirmed diagnosis of previously untreated, operable, and measurable primary breast cancer (tumour (T), nodes (N) and metastases (M) score: T2-3(>= 3 cm) N0-2 M0) were treated in a prospectively randomised trial with four cycles of dose-dense (bi-weekly) doxorubicin and docetaxel (ddAT) chemotherapy, with or without tamoxifen, prior to surgery. Clinical and pathological parameters (menopausal status, clinical tumour size and nodal status, grade, and clinical response after two cycles) and a panel of biomarkers (oestrogen and progesterone receptors, Ki-67, human epidermal growth factor receptor 2 (HER2), p53, bcl-2, all detected by immunohistochemistry) were correlated with the detection of a pathological complete response (pCR). Results A pCR was observed in 9.7% in 248 patients randomised in the study and in 8.6% in the subset of 196 patients with available tumour tissue. Clinically negative axillary lymph nodes, poor tumour differentiation, negative oestrogen receptor status, negative progesterone receptor status, and loss of bcl-2 were significantly predictive for a pCR in a univariate logistic regression model, whereas in a multivariate analysis only the clinical nodal status and hormonal receptor status provided significantly independent information. Backward stepwise logistic regression revealed a response after two cycles, with hormone receptor status and lymph-node status as significant predictors. Patients with a low percentage of cells stained positive for Ki-67 showed a better response when treated with tamoxifen, whereas patients with a high percentage of Ki-67 positive cells did not have an additional benefit when treated with tamoxifen. Tumours overexpressing HER2 showed a similar response to that in HER2-negative patients when treated without tamoxifen, but when HER2-positive tumours were treated with tamoxifen, no pCR was observed. Conclusion Reliable prediction of a pathological complete response after preoperative chemotherapy is not possible with clinical and biological factors routinely determined before start of treatment. The response after two cycles of chemotherapy is a strong but dependent predictor. The only independent factor in this subset of patients was bcl-2. Trial registration number NCT0054382