Outcome of ovarian cancer after breast cancer in BRCA1 and BRCA2 mutation carriers

Background: It is unknown whether a history of breast cancer (BC) affects the outcome of BRCA1/2-associated epithelial ovarian cancer (EOC). This was investigated in the current analysis. Methods: We included 386 BRCA1/2-associated EOC patients diagnosed between 1980 and 2015. Progression-free survival (PFS), progression-free interval (PFI), overall survival (OS) and ovarian cancer-specific survival (OCSS) were compared between EOC patients with and without previous BC. Results: BRCA-associated EOC patients with, vs without, a BC history had a significantly worse PFS and PFI (multivariate hazard ratio (HRmult) 1.47; 95% confidence interval (CI) 1.03-2.08 and HRmult 1.43; 95% CI 1.01-2.03), and a non-significantly worse OS (HRmult 1.15; 95% CI 0.84-1.57) and OCSS (HRmult 1.18; 95% CI 0.85-1.62). Ovarian cancer-specific survival was significantly worse for the subgroup treated with adjuvant chemotherapy for BC (HRmult 1.99; 95% CI 1.21-3.31). Conclusions: Our results suggest that BRCA1/2-associated EOC patients with a previous BC have a worse outcome than EOC patients without BC, especially when treated with adjuvant chemotherapy

Sex differences in oncogenic mutational processes.

Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research

Reputational risk as a logic of organizing in late modernity

Post-print version. Final version published by Sage; available online at http://oss.sagepub.com/This paper argues that it is useful to regard `reputational risk' as a pervasive logic of organizing and organizational attention. First, we suggest that the risk management agenda has expanded from its roots in technical analysis to become a cornerstone of good governance and responsible actorhood. We illustrate this claim in the context of English universities. Second, we suggest that this expansion in the reach and significance of risk management has increased organizational orientations to reputational risk and to more defensively and legalistically framed forms of asset management. Specifically, organizations are responding to the growth of external bodies which evaluate and rank, and thereby generate reputational risk. In the context of universities, we argue that this leads both to specific transformations in organizational practices in response to ranking systems, and also to an increased generalized concern with reputational risk, which is a symptom of late modern insecurity

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

The wall street journal on marketing/ Alsop

x, 294 hal. ; 23 c

The wall street journal on marketing/ Alsop

x, 294 hal. ; 23 c