2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial

BACKGROUND Trastuzumab has established efficacy against breast cancer with overexpression or amplification of the HER2 oncogene. The standard of care is 1 year of adjuvant trastuzumab, but the optimum duration of treatment is unknown. We compared 2 years of treatment with trastuzumab with 1 year of treatment, and updated the comparison of 1 year of trastuzumab versus observation at a median follow-up of 8 years, for patients enrolled in the HERceptin Adjuvant (HERA) trial. METHODS The HERA trial is an international, multicentre, randomised, open-label, phase 3 trial comparing treatment with trastuzumab for 1 and 2 years with observation after standard neoadjuvant chemotherapy, adjuvant chemotherapy, or both in 5102 patients with HER2-positive early breast cancer. The primary endpoint was disease-free survival. The comparison of 2 years versus 1 year of trastuzumab treatment involved a landmark analysis of 3105 patients who were disease-free 12 months after randomisation to one of the trastuzumab groups, and was planned after observing at least 725 disease-free survival events. The updated intention-to-treat comparison of 1 year trastuzumab treatment versus observation alone in 3399 patients at a median follow-up of 8 years (range 0-10) is also reported. This study is registered with ClinicalTrials.gov, number NCT00045032. FINDINGS We recorded 367 events of disease-free survival in 1552 patients in the 1 year group and 367 events in 1553 patients in the 2 year group (hazard ratio [HR] 0·99, 95% CI 0·85-1·14, p=0·86). Grade 3-4 adverse events and decreases in left ventricular ejection fraction during treatment were reported more frequently in the 2 year treatment group than in the 1 year group (342 [20·4%] vs 275 [16·3%] grade 3-4 adverse events, and 120 [7·2%] vs 69 [4·1%] decreases in left ventricular ejection fraction, respectively). HRs for a comparison of 1 year of trastuzumab treatment versus observation were 0·76 (95% CI 0·67-0·86, p<0·0001) for disease-free survival and 0·76 (0·65-0·88, p=0·0005) for overall survival, despite crossover of 884 (52%) patients from the observation group to trastuzumab therapy. INTERPRETATION 2 years of adjuvant trastuzumab is not more effective than is 1 year of treatment for patients with HER2-positive early breast cancer. 1 year of treatment provides a significant disease-free and overall survival benefit compared with observation and remains the standard of care. FUNDING F Hoffmann-La Roche (Roche).

Michael Salomon Alexander der erste evangelische Bischof in Jerusalem : ein Beitrag zur orientalischen Frage

von J. F. A. de Le Roi

Discontinuity in the responses of ecosystem processes and multifunctionality to altered soil community composition

Ecosystem management policies increasingly emphasize provision of multiple, as opposed to single, ecosystem services. Management for such "multifunctionality" has stimulated research into the role that biodiversity plays in providing desired rates of multiple ecosystem processes. Positive effects of biodiversity on indices of multifunctionality are consistently found, primarily because species that are redundant for one ecosystem process under a given set of environmental conditions play a distinct role under different conditions or in the provision of another ecosystem process. Here we show that the positive effects of diversity (specifically community composition) on multifunctionality indices can also arise from a statistical fallacy analogous to Simpson's paradox (where aggregating data obscures causal relationships). We manipulated soil faunal community composition in combination with nitrogen fertilization of model grassland ecosystems and repeatedly measured five ecosystem processes related to plant productivity, carbon storage, and nutrient turnover. We calculated three common multifunctionality indices based on these processes and found that the functional complexity of the soil communities had a consistent positive effect on the indices. However, only two of the five ecosystem processes also responded positively to increasing complexity, whereas the other three responded neutrally or negatively. Furthermore, none of the individual processes responded to both the complexity and the nitrogen manipulations in a manner consistent with the indices. Our data show that multifunctionality indices can obscure relationships that exist between communities and key ecosystem processes, leading us to question their use in advancing theoretical understanding-and in management decisions-about how biodiversity is related to the provision of multiple ecosystem services.

Glauben als Grundlage - Die Rezeption Michael Polanyis im Gespräch von Theologie und Naturwissenschaften

Das Konzept des „Glaubens“ ist eine zentrale Grundlage von Polanyis Wissenschaftstheorie, und schon früh hat er sich explizit mit dem Verhältnis von Religion und Wissenschaft beschäftigt. Entsprechend wohlwollend ist seine Philosophie im Gespräch von Theologie und Naturwissenschaften aufgenommen worden. Seine deutschsprachige Rezeption blieb dabei bislang recht spärlich, während er in dem angelsächsischen Gespräch der Wissenschaften früh reiche Wirkung entfaltet und nahezu paradigmatische Bedeutung gewonnen hat. Die 2005 erschienene umfangreiche Polanyibiographie von William T. Scott und Martin X. Moleski, S.J. informiert auch über die Facetten von Polanyis eigenen Glauben. Sie stellt damit eine wesentliche Interpretationshilfe da, wie man eine Streitfrage der angelsächsischen Polanyi-Rezeption betreffs der Realität des Gegenstandes der Religion in seiner Philosophie beurteilen kann. Es ist davon auszugehen, dass er mit Tillich den Existenzbegriff in seiner Anwendung auf Gott abgelehnt hat und die Gelwick/Torrance-Prosch-Debatte, die um die Frage der unabhängigen Existenz Gottes in Polanyis Denken kreist, deswegen mehr oder weniger sinnlos ist.

Über Aus- und Rückwanderung : Vortrag, geh. am Mittwoch, 17. Sept. 1902 in d. Henry Jones-Loge in Hamburg

von Paul Laskar