“It was an important part of my treatment”: a qualitative study of Norwegian breast Cancer patients’ experiences with mainstreamed genetic testing

Background In South-Eastern Norway, genetic testing for BRCA1 and BRCA2 is offered to breast cancer patients by their treating surgeon or oncologist. Genetic counselling from a geneticist or a genetic counsellor is offered only to those who test positive for a pathogenic variant or have a family history of cancer. This practice is termed “mainstreamed genetic testing”. The aim of this study was to learn about patients’ experience of this healthcare service. Methods Qualitative in-depth interviews were conducted with 22 breast cancer patients who had been diagnosed during the first half of 2016 or 2017 at one regional and one university hospital and who had been offered testing by their treating physician. A six-phase thematic approach was used to analyse the data. Results The participants had varied experiences of how and when testing was offered. Three main themes emerged from the analysis: 1. informational and communicational needs and challenges during a chaotic time, 2. the value of genetic testing and 3. the importance of standardised routines for mainstreamed genetic testing. Conclusions Despite the shock of their diagnosis and the varying experiences they had in respect of how and when testing was offered, all of the participants emphasised that genetic testing had been an important part of their diagnosis and treatment. Our results indicate that there is a need for continuous collaboration between geneticists, surgeons, oncologists and laboratory specialists in order to establish simple and robust routines so as to ensure that all eligible breast cancer patients are offered testing at a point when the test result can have an impact on treatment

“It was an important part of my treatment”: a qualitative study of Norwegian breast Cancer patients’ experiences with mainstreamed genetic testing

Background: In South-Eastern Norway, genetic testing for BRCA1 and BRCA2 is offered to breast cancer patients by their treating surgeon or oncologist. Genetic counselling from a geneticist or a genetic counsellor is offered only to those who test positive for a pathogenic variant or have a family history of cancer. This practice is termed “mainstreamed genetic testing”. The aim of this study was to learn about patients’ experience of this healthcare service. Methods: Qualitative in-depth interviews were conducted with 22 breast cancer patients who had been diagnosed during the first half of 2016 or 2017 at one regional and one university hospital and who had been offered testing by their treating physician. A six-phase thematic approach was used to analyse the data. Results: The participants had varied experiences of how and when testing was offered. Three main themes emerged from the analysis: 1. informational and communicational needs and challenges during a chaotic time, 2. the value of genetic testing and 3. the importance of standardised routines for mainstreamed genetic testing. Conclusions: Despite the shock of their diagnosis and the varying experiences they had in respect of how and when testing was offered, all of the participants emphasised that genetic testing had been an important part of their diagnosis and treatment. Our results indicate that there is a need for continuous collaboration between geneticists, surgeons, oncologists and laboratory specialists in order to establish simple and robust routines so as to ensure that all eligible breast cancer patients are offered testing at a point when the test result can have an impact on treatment

Impact of Prosigna test on adjuvant treatment decision in lymph node-negative early breast cancer—a prospective national multicentre study (EMIT-1)

Background: EMIT-1 is a national, observational, single-arm trial designed to assess the value of the Prosigna, Prediction Analysis of Microarray using the 50 gene classifier (PAM50)/Risk of Recurrence (ROR), test as a routine diagnostic tool, examining its impact on adjuvant treatment decisions, clinical outcomes, side-effects and cost-effectiveness. Here we present the impact on treatment decisions. Patients and methods: Patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative pT1-pT2 lymph node-negative early breast cancer (EBC) were included. The Prosigna test and standard histopathology assessments were carried out. Clinicians’ treatment decisions were recorded before (pre-Prosigna) and after (postProsigna) the Prosigna test results were disclosed. Results: Of 2217 patients included, 2178 had conclusive Prosigna results. The pre-Prosigna treatment decisions were: no systemic treatment (NT) in 27% of patients, endocrine treatment alone (ET) in 38% and chemotherapy (CT) followed by ET (CT þ ET) in 35%. Post-Prosigna treatment decisions were 25% NT, 51% ET and 24% CT þ ET, respectively. Adjuvant treatment changed in 28% of patients, including 21% change in CT use. Among patients assigned to CT þ ET preProsigna, 45% were de-escalated to ET post-Prosigna. Of patients assigned to ET, 12% were escalated to CT þ ET and 8% were de-escalated to NT; of those assigned to NT, 18% were escalated to ET/CT þ ET. CT was more frequently recommended for patients aged 50 years. In the subgroup with pT1c-pT2 G2 and intermediate Ki67 (0.5- 1.5 local laboratory median Ki67 score), the pre-Prosigna CT treatment decision varied widely across hospitals (3%- 51%). Post-Prosigna, the variability of CT use was markedly reduced (8%-24%). The correlation between Ki67 and ROR score within this subgroup was poor (r ¼ 0.25-0.39). The median ROR score increased by increasing histological grade, but the ROR score ranges were wide (for G1 0-79, G2 0-90, G3 16-94). Conclusion: The Prosigna test result changed adjuvant treatment decisions in all EBC clinical risk groups, markedly decreased the CT use for patients categorized as higher clinical risk pre-Prosigna and reduced treatment decision discrepancies between hospitals

Combined sequence-based and genetic mapping analysis of complex traits in outbred rats

<p>Genetic mapping on fully sequenced individuals is transforming understanding of the relationship between molecular variation and variation in complex traits. Here we report a combined sequence and genetic mapping analysis in outbred rats that maps 355 quantitative trait loci for 122 phenotypes. We identify 35 causal genes involved in 31 phenotypes, implicating new genes in models of anxiety, heart disease and multiple sclerosis. The relationship between sequence and genetic variation is unexpectedly complex: at approximately 40% of quantitative trait loci, a single sequence variant cannot account for the phenotypic effect. Using comparable sequence and mapping data from mice, we show that the extent and spatial pattern of variation in inbred rats differ substantially from those of inbred mice and that the genetic variants in orthologous genes rarely contribute to the same phenotype in both species.</p>

Homomorphisms and Ramsey properties of antimatroids

SIGLEBibliothek Weltwirtschaft Kiel C132,202 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

haplotype_dosages_Rnor50.tar.gz

Probabilities of descent (haplotype dosages) of 1,407 Heterogenous Stock rat from each of the eight progenitors of the Stock, at each locus in the genom

measures.txt

216 phenotypes and experimental covariates measured in 2,006 NIH Heterogeneous Stock rat

merge_factors.RData

sequence variants (SNPs and indels) in all eight founder strains of the Heterogeneous Stock, formatted in an R object for merge analysi

Supplementary Table 2. Results of phosphoprotein measurements in primary normal human bronchial epithelial cells (NHBE) and normal rat bronchial epithelial cells (NRBE) using antibody-bead based assays for the experimental screening of 270 stimuli.

Supplementary Table 2. Results of phosphoprotein measurements in primary normal human bronchial epithelial cells (NHBE) and normal rat bronchial epithelial cells (NRBE) using antibody-bead based assays for the experimental screening of 270 stimuli. After an exposure of 5 minutes to each stimulus, cells were lysed and used to measure phosphoproteins. Data were analyzed and a final selection of 52 stimuli used for the main experiment was performed (Data deposited in the figshare public repository)