Summary We analyzed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, mRNA arrays, microRNA sequencing and reverse phase protein arrays. Our ability to integrate information across platforms provided key insights into previously-defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity. Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at > 10% incidence across all breast cancers; however, there were numerous subtype-associated and novel gene mutations including the enrichment of specific mutations in GATA3, PIK3CA and MAP3K1 with the Luminal A subtype. We identified two novel protein expression-defined subgroups, possibly contributed by stromal/microenvironmental elements, and integrated analyses identified specific signaling pathways dominant in each molecular subtype including a HER2/p-HER2/HER1/p-HER1 signature within the HER2-Enriched expression subtype. Comparison of Basal-like breast tumors with high-grade Serous Ovarian tumors showed many molecular commonalities, suggesting a related etiology and similar therapeutic opportunities. The biologic finding of the four main breast cancer subtypes caused by different subsets of genetic and epigenetic abnormalities raises the hypothesis that much of the clinically observable plasticity and heterogeneity occurs within, and not across, these major biologic subtypes of breast cancer.

Summary Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3 and FOXA1 as ILC enriched features. PTEN loss associated with increased AKT phosphorylation, which was highest in ILC among all breast cancer subtypes. Spatially clustered FOXA1 mutations correlated with increased FOXA1 expression and activity. Conversely, GATA3 mutations and high expression characterized Luminal A IDC, suggesting differential modulation of ER activity in ILC and IDC. Proliferation and immune-related signatures determined three ILC transcriptional subtypes associated with survival differences. Mixed IDC/ILC cases were molecularly classified as ILC-like and IDC-like revealing no true hybrid features. This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options.

Purpose: ASCO projects a shortfall of oncologists in the next decade. The study was designed to address the workforce shortage by exploring collaborative oncology practice models that include nonphysician practitioners (NPPs).Methods: ASCO contracted with Oncology Metrics, a division of Altos Solutions, to conduct a national survey of NPP integration and identify collaborative practice models and services provided by NPPs, as the first phase of the ASCO Study of Collaborative Practice Arrangements. Results of the national survey were used to identify practices for the next phase, in which selected practices participated in a more detailed data survey and satisfaction surveys. Focus groups or interviews were conducted with NPPs to collect additional subjective information to inform the project. Results:The incident-to practice model was the predominant model. Satisfaction was universally high for patients and generally high for physicians and NPPs. In virtually all cases (98%), patients recognized they were seeing an NPP rather than a physician. Practices in which the NPP worked with all practice physicians showed significantly higher productivity than those practices in which the NPP worked exclusively with a specific physician or group of physicians. Conclusion:The use of NPPs in oncology practices increases productivity for the practice and provides high physician and NPP satisfaction. Patients were aware when care was provided by an NPP and were very satisfied with all aspects of the collaborative care that they received. The integration of nonphysician practitioners into oncology practice offers a reliable means to address increased demand for oncology services without adding physicians.

This paper explores the way in which announcers created spectacle in the Eurosport coverage of the men's and women's tennis singles semifinals and finals at the Australian Open 2015. This was an event where gender representations were under global social media scrutiny after two female players were asked to 'twirl' for the audience. We used a two-phase thematic analysis. Semantic thematic analysis showed that more personal descriptions were directed at women than men and these often described off-court features. Descriptions of men included detailed and specific portrayals of physical characteristics, while women's bodies were seldom referred to specifically. Discourse analysis showed that men's games were spoken of as physical clashes between titans. In contrast, women's matches were described in aesthetic rather than physical terms and 'divalike' personalities and relationships were important features of women's game narratives. While male bodies were described in specific detail where relevant to technical features of the game, women's bodies were only described indirectly and non-specifically. For the women's game, this dialogical repression of specific body talk in combination with a strong focus on aesthetic judgements invoked stereotypes by omission, simultaneously reinscribing gender stereotypes and

Whole slide imaging (WSI) is rapidly transforming educational and diagnostic pathology services. Recently, the College of American Pathologists Pathology and Laboratory Quality Center (CAP-PLQC) published recommended guidelines for validating diagnostic WSI. We prospectively evaluated the guidelines to determine their utility in validating pediatric surgical pathology and cytopathology specimens. Our validation included varied pediatric specimen types, including complex or less common diagnoses, in accordance with the guidelines. We completed WSI review of 60 surgical pathology cases and attempted WSI review of 21 cytopathology cases. For surgical pathology cases, WSI diagnoses were highly concordant with glass slide diagnoses; a discordant diagnosis was observed in 1 of 60 cases (98.3% concordance). We found that nucleated red blood cells and eosinophilic granular bodies represented specific challenges to WSI review of pediatric specimens. Cytology specimens were more frequently discordant or failed for technical reasons, with overall concordance of 66.7%. Review of pediatric cytopathology specimens will likely require image capture in multiple focal planes. This study is the first to specifically evaluate WSI review for pediatric specimens and demonstrates that specimens representing the spectrum of pediatric surgical pathology practice can be reviewed using WSI. Our application of the proposed CAP-PLQC guidelines to pediatric surgical pathology specimens is, to our knowledge, the first prospective implementation of the CAP-PLQC guidelines.