A randomized trial of three videos that differ in the framing of information about mammography in women 40 to 49 years old

OBJECTIVE: To assess the effect of providing structured information about the benefits and harms of mammography in differing frames on women’s perceptions of screening. DESIGN: Randomized control trial. SETTING: General internal medicine academic practice. PARTICIPANTS: One hundred seventy-nine women aged 35 through 49. INTERVENTION: Women received 1 of 3 5-minute videos about the benefits and harms of screening mammography in women aged 40 to 49. These videos differed only in the way the probabilities of potential outcomes were framed (positive, neutral, or negative). MEASUREMENTS AND MAIN RESULTS: We measured the change in accurate responses to questions about potential benefits and harms of mammography, and the change in the proportion of participants who perceived that the benefits of mammography were more important than the harms. Before seeing the videos, women’s knowledge about the benefits and harms of mammography was inaccurate (82% responded incorrectly to all 3 knowledge questions). After seeing the videos, the proportion that answered correctly increased by 52%, 43%, and 30% for the 3 knowledge questions, respectively, but there were no differences between video frames. At baseline, most women thought the benefits of mammography outweighed the harms (79% positive frame, 80% neutral frame, and 85% negative frame). After the videos, these proportions were similar among the 3 groups (84%, 81%, 83%, P = .93). CONCLUSIONS: Women improved the accuracy of their responses to questions about the benefits and harms of mammography after seeing the videos, but this change was not affected by the framing of information. Women strongly perceived that the benefits of mammography outweighed the harms, and providing accurate information had no effect on these perceptions, regardless of how it was framed

Proteome Profiling Outperforms Transcriptome Profiling for Coexpression Based Gene Function Prediction

Coexpression of mRNAs under multiple conditions is commonly used to infer cofunctionality of their gene products despite well-known limitations of this “guilt-by-association” (GBA) approach. Recent advancements in mass spectrometry-based proteomic technologies have enabled global expression profiling at the protein level; however, whether proteome profiling data can outperform transcriptome profiling data for coexpression based gene function prediction has not been systematically investigated. Here, we address this question by constructing and analyzing mRNA and protein coexpression networks for three cancer types with matched mRNA and protein profiling data from The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC). Our analyses revealed a marked difference in wiring between the mRNA and protein coexpression networks. Whereas protein coexpression was driven primarily by functional similarity between coexpressed genes, mRNA coexpression was driven by both cofunction and chromosomal colocalization of the genes. Functionally coherent mRNA modules were more likely to have their edges preserved in corresponding protein networks than functionally incoherent mRNA modules. Proteomic data strengthened the link between gene expression and function for at least 75% of Gene Ontology (GO) biological processes and 90% of KEGG pathways. A web application Gene2Net (http://cptac.gene2net.org) developed based on the three protein coexpression networks revealed novel gene-function relationships, such as linking ERBB2 (HER2) to lipid biosynthetic process in breast cancer, identifying PLG as a new gene involved in complement activation, and identifying AEBP1 as a new epithelial-mesenchymal transition (EMT) marker. Our results demonstrate that proteome profiling outperforms transcriptome profiling for coexpression based gene function prediction. Proteomics should be integrated if not preferred in gene function and human disease studies

Documentation of preventive screening interventions by general practitioners: a retrospective chart audit

<p>Abstract</p> <p>Background</p> <p>Screening and early diagnosis has been shown to reduce the morbidity and mortality associated with certain conditions such as cervical cancer. The role of general practitioners in promoting primary prevention of diseases is particularly important given that they have frequent contact with a large proportion of the population. This study assessed the extent to which general practitioners documented recommended preventive screening interventions among eligible patients.</p> <p>Methods</p> <p>We used a retrospective chart audit to assess patient visits to primary care clinics in Calgary, Canada from 2002-2004. We included fee for service physicians who practiced ≥ 2 days per week at their current location and excluded those whose primary practice was at walk-in clinics, community health centers, hospitals or emergency rooms. We included charts of patients who during the study period were age 35 years or older and had at least 2 visits to a clinic. We randomly selected and reviewed charts (N = 600) from 12 primary care clinics and abstracted information on 6 conditions recommended for preventive screening. Opportunities for preventive screening were determined based on recommendations of the Canadian Task Force on Preventive Health Care, the American College of Physicians, and the Canadian Cancer Society. Our main outcome measures included cancer screening (mammography and pap smears), immunization (influenza and pneumococcal), and risk factor assessment (cholesterol measurement and smoking cessation consultation).</p> <p>Results</p> <p>Patient visits to GP clinics present opportunities for preventive screening. However, we found that documentation of interventions was low, ranging from 40.3% (cholesterol measurement) to 0.9% (pneumococcal vaccination) within 1 year, and from 67.4% to 1.8% within the prior 3 years.</p> <p>Conclusions</p> <p>Documentation of preventive screening interventions by general practitioners was relatively low compared to the number of patients eligible for preventive screening. Some physicians opt to screen for PSA and DRE which is not recommended by the Canadian Task Force on Preventive HealthCare.</p

Reproducibility of differential proteomic technologies in CPTAC fractionated xenografts

The NCI Clinical Proteomic Tumor Analysis Consortium (CPTAC) employed a pair of reference xenograft proteomes for initial platform validation and ongoing quality control of its data collection for The Cancer Genome Atlas (TCGA) tumors. These two xenografts, representing basal and luminal-B human breast cancer, were fractionated and analyzed on six mass spectrometers in a total of 46 replicates divided between iTRAQ and label-free technologies, spanning a total of 1095 LC-MS/MS experiments. These data represent a unique opportunity to evaluate the stability of proteomic differentiation by mass spectrometry over many months of time for individual instruments or across instruments running dissimilar workflows. We evaluated iTRAQ reporter ions, label-free spectral counts, and label-free extracted ion chromatograms as strategies for data interpretation (source code is available from http://homepages.uc.edu/~wang2x7/Research.htm). From these assessments, we found that differential genes from a single replicate were confirmed by other replicates on the same instrument from 61 to 93% of the time. When comparing across different instruments and quantitative technologies, using multiple replicates, differential genes were reproduced by other data sets from 67 to 99% of the time. Projecting gene differences to biological pathways and networks increased the degree of similarity. These overlaps send an encouraging message about the maturity of technologies for proteomic differentiation

Proteogenomic analysis of human colon cancer reveals new therapeutic opportunities

We performed the first proteogenomic study on a prospectively collected colon cancer cohort. Comparative proteomic and phosphoproteomic analysis of paired tumor and normal adjacent tissues produced a catalog of colon cancer-associated proteins and phosphosites, including known and putative new biomarkers, drug targets, and cancer/testis antigens. Proteogenomic integration not only prioritized genomically inferred targets, such as copy-number drivers and mutation-derived neoantigens, but also yielded novel findings. Phosphoproteomics data associated Rb phosphorylation with increased proliferation and decreased apoptosis in colon cancer, which explains why this classical tumor suppressor is amplified in colon tumors and suggests a rationale for targeting Rb phosphorylation in colon cancer. Proteomics identified an association between decreased CD8 T cell infiltration and increased glycolysis in microsatellite instability-high (MSI-H) tumors, suggesting glycolysis as a potential target to overcome the resistance of MSI-H tumors to immune checkpoint blockade. Proteogenomics presents new avenues for biological discoveries and therapeutic development

Australian clinicians and chemoprevention for women at high familial risk for breast cancer

<p>Abstract</p> <p>Objectives</p> <p>Effective chemoprevention strategies exist for women at high risk for breast cancer, yet uptake is low. Physician recommendation is an important determinant of uptake, but little is known about clinicians' attitudes to chemoprevention.</p> <p>Methods</p> <p>Focus groups were conducted with clinicians at five Family Cancer Centers in three Australian states. Discussions were recorded, transcribed and analyzed thematically.</p> <p>Results</p> <p>Twenty three clinicians, including genetic counselors, clinical geneticists, medical oncologists, breast surgeons and gynaecologic oncologists, participated in six focus groups in 2007. The identified barriers to the discussion of the use of tamoxifen and raloxifene for chemoprevention pertained to issues of evidence (evidence for efficacy not strong enough, side-effects outweigh benefits, oophorectomy superior for mutation carriers), practice (drugs not approved for chemoprevention by regulatory authorities and not government subsidized, chemoprevention not endorsed in national guidelines and not many women ask about it), and perception (clinicians not knowledgeable about chemoprevention and women thought to be opposed to hormonal treatments).</p> <p>Conclusion</p> <p>The study demonstrated limited enthusiasm for discussing breast cancer chemoprevention as a management option for women at high familial risk. Several options for increasing the likelihood of clinicians discussing chemoprevention were identified; maintaining up to date national guidelines on management of these women and education of clinicians about the drugs themselves, the legality of "off-label" prescribing, and the actual costs of chemopreventive medications.</p

Proteogenomic integration reveals therapeutic targets in breast cancer xenografts

Recent advances in mass spectrometry (MS) have enabled extensive analysis of cancer proteomes. Here, we employed quantitative proteomics to profile protein expression across 24 breast cancer patient-derived xenograft (PDX) models. Integrated proteogenomic analysis shows positive correlation between expression measurements from transcriptomic and proteomic analyses; further, gene expression-based intrinsic subtypes are largely re-capitulated using non-stromal protein markers. Proteogenomic analysis also validates a number of predicted genomic targets in multiple receptor tyrosine kinases. However, several protein/phosphoprotein events such as overexpression of AKT proteins and ARAF, BRAF, HSP90AB1 phosphosites are not readily explainable by genomic analysis, suggesting that druggable translational and/or post-translational regulatory events may be uniquely diagnosed by MS. Drug treatment experiments targeting HER2 and components of the PI3K pathway supported proteogenomic response predictions in seven xenograft models. Our study demonstrates that MS-based proteomics can identify therapeutic targets and highlights the potential of PDX drug response evaluation to annotate MS-based pathway activities