Clinicopathological features and BRCA1 and BRCA2 mutation status in a prospective cohort of young women with breast cancer

Background Breast cancer in young women is more likely to have higher risk features and be associated with germline BRCA1/BRCA2 mutations. We present the clinicopathologic features of breast cancers in a prospective cohort of young women, and associations between surrogate molecular subtype and BRCA1/BRCA2 mutation status. Methods Histopathological features, biomarker status, tumour stage and BRCA status were collected. Invasive tumours were categorised as luminal A-like (ER + and/or PR + , HER2-, grade 1/2), luminal B-like (ER + and/or PR + , HER2 + , or ER + and/or PR + , HER2-, and grade 3), HER2-enriched (ER/PR-, HER2 + ) or triple-negative. Results In all, 57.3% (654/1143) of invasive tumours were high grade. In total, 32.9% were luminal A-like, 42.4% luminal B-like, 8.3% HER2-enriched, and 16.4% triple-negative. Among different age groups, there were no differences in molecular phenotype, stage, grade or histopathology. 11% (131) of tumours were from BRCA mutation carriers; 64.1% BRCA1 (63.1% triple-negative), and 35.9% BRCA2 (55.3% luminal B-like). Discussion The opportunity to provide comparisons across young age groups, BRCA mutation status, surrogate molecular phenotype, and the identification of more aggressive hormone receptor-positive phenotypes in this population provides direction for future work to further understand and improve disparate outcomes for young women with luminal B-like cancers, particularly BRCA2-associated cancers, with potential implications for tailored prevention and treatment

Deep brain stimulation in early Parkinson’s disease: Enrollment experience from a pilot trial

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus is an accepted therapy for advanced Parkinson’s disease (PD). In animal models, pharmacologic ablation and stimulation of the subthalamic nucleus have resulted in clinical improvement and, in some cases, improved survival of dopaminergic neurons. DBS has not been studied in the early stages of PD, but early application should be explored to evaluate safety, efficacy, and the potential to alter disease progression. METHODS: We are conducting a prospective, randomized, single-blind clinical trial of optimal drug therapy (ODT) compared to medication plus DBS (ODT + DBS) in subjects with Hoehn & Yahr Stage II idiopathic PD who are without motor fluctuations or dementia. We report here subject screening, enrollment, baseline characteristics, and adverse events. RESULTS: 30 subjects (average age 60 ± 6.9 years, average duration of medicine 2.1 ± 1.3 years, average UPDRS-III scores 14.9 on medication and 27.0 off medication) are enrolled in the ongoing study. Twelve of 15 subjects randomized to DBS experienced perioperative adverse events, the majority of which were related to the procedure or device and resolved without sequelae. Frequently reported adverse events included wound healing problems, headache, edema, and confusion. CONCLUSION: This report demonstrates that subjects with early stage PD can be successfully recruited, consented and retained in a long term clinical trial of DBS. Our ongoing pilot investigation will provide important preliminary safety and tolerability data concerning the application of DBS in early stage PD

Das Gleichwertigkeitsaudit

Becker J, Franke K, Gelöz O, et al. Das Gleichwertigkeitsaudit. In: Reflektieren. Erkennen. Verändern. Was tun gegen Gruppenbezogene Menschenfeindlichkeit?. Berlin: Amadeu Antonio Stiftung; 2007: 18-15

An Extraterritorial FDA: Could the Food and Drug Administration Apply Its Informed Consent Requirement Abroad Consistent with International Law?

This paper addresses the regulatory challenges wrought by the increasing amount of human subject drug testing conducted in developing countries in support of new drug applications to the Food and Drug Administration. Specifically, it examines the difficulty of enforcing the “informed consent” requirement for ethical scientific research performed in foreign territory. In poorer regions, a lack of government oversight, lower regulatory standards, and barriers to communication have too frequently resulted in allegations of human experimentation performed without its participants’ informed consent. In order to solve this problem, some commentators have suggested that the FDA could apply its human subject protections to foreign clinical research, and enforce them through injunctions or criminal prosecutions. However, the international legal limits on states’ prescriptive jurisdiction may prohibit this exercise of extraterritoriality. After analyzing the proposed extraterritorial regulation of foreign drug testing under the traditional bases and limitations of prescriptive jurisdiction, this paper concludes that such regulation would likely violate international law. However, because nonconsensual clinical research has previously been regarded as a crime against humanity, the FDA might be able to bring criminal prosecutions under the principal of “universal jurisdiction” against investigators or sponsors who conducted studies without their subjects’ informed consent. This analysis offers both positive and normative conclusions regarding the international legal system and the human rights regime