Multiomics in primary and metastatic breast tumors from the AURORA US network finds microenvironment and epigenetic drivers of metastasis.

The AURORA US Metastasis Project was established with the goal to identify molecular features associated with metastasis. We assayed 55 females with metastatic breast cancer (51 primary cancers and 102 metastases) by RNA sequencing, tumor/germline DNA exome and low-pass whole-genome sequencing and global DNA methylation microarrays. Expression subtype changes were observed in ~30% of samples and were coincident with DNA clonality shifts, especially involving HER2. Downregulation of estrogen receptor (ER)-mediated cell-cell adhesion genes through DNA methylation mechanisms was observed in metastases. Microenvironment differences varied according to tumor subtype; the ER+/luminal subtype had lower fibroblast and endothelial content, while triple-negative breast cancer/basal metastases showed a decrease in B and T cells. In 17% of metastases, DNA hypermethylation and/or focal deletions were identified near HLA-A and were associated with reduced expression and lower immune cell infiltrates, especially in brain and liver metastases. These findings could have implications for treating individuals with metastatic breast cancer with immune- and HER2-targeting therapies.

Opioid Prescribing and Use Among Cancer Survivors: A Mapping Review of Observational and Intervention Studies.

CONTEXT: Recent years show a sharp increase in research on opioid use among cancer survivors, but evidence syntheses are lacking, leaving knowledge gaps. Corresponding research needs are unclear. OBJECTIVES: To provide an evidence synthesis. METHODS: We searched PubMed and Embase, identifying articles related to cancer, and opioid prescribing/use published through September 2020. We screened resulting titles/abstracts. Relevant studies underwent full-text review. Inclusion criteria were quantitative examination of and primary focus on opioid prescribing or use, and explicit inclusion of cancer survivors. Exclusion criteria included end-of-life opioid use and opioid use as a secondary or downstream outcome (for intervention studies). We extracted information on the opioid-related outcome(s) examined (including definitions and terminology used), study design, and methods. RESULTS: Research returned 16,591 articles; 296 were included. Only 22 of 296 studies evaluated an intervention. There were 105 studies evaluating outcomes indicative of potentially high-risk, nonrecommended, or avoidable opioid use, e.g., continuous use-described as chronic use, prolonged use, and persistent use (n = 17); use after completion of curative-intent treatment-described as chronic opioid use, long-term opioid use, persistent opioid use, prolonged opioid use, continued opioid use, late opioid use, post-treatment opioid use (n = 27); use of opioids concurrent with other potentially high-risk medications (n = 13), and opioid misuse (n = 14). CONCLUSIONS: We found lack of consistency in the measurement of and terms used to describe similar opioid use outcomes, and a lack of interventional research targeting well-documented patterns of potentially nonrecommended, potentially avoidable, or potentially high-risk opioid prescribing or use.

Physician experiences of screen-level features in a prominent electronic health record: Design recommendations from a qualitative study.

The goal of this qualitative study was to assess physicians' perceptions around features of key screens within a prominent commercial EHR, and to solicit end-user recommendations for improved retrieval of high-priority clinical information. We conducted a qualitative, descriptive study of 25 physicians in a medical ICU setting. at a tertiary academic medical center. An in-depth, semi-structured interview guide was developed to elicit physician perceptions on information retrieval as well as favorable and unfavorable features of specific EHR screens. Transcripts were independently coded in a qualitative software management tool by at least two trained coders using a common code book. We successfully obtained vendor permission to map physicians perception's on full Epic© screenshots. Among the 25 physician participants (13 female; 5 attending physicians, 9 fellows, 11 residents), the majority of participants reported experiencing challenges finding clinical information in the EHR. We present the most favorable and unfavorable screen-level features for four central EHR screens: Flowsheet, Notes/Chart Review, Results Review, and Vital Signs. We also compiled participants' recommendations for a comprehensive EHR dashboard screen to better support clinical workflow and information retrieval in the medical ICU through User-Centered Design. ICU physicians demonstrated a mix of positive and negative attitudes toward specific screen-level features in a major vendor-based EHR system. Physician perceptions of information overload emerged as a theme across multiple EHR screens. Our findings underscore the importance of qualitative research and end-user feedback in EHR software design and interface optimization at both the vendor and institutional level.