Circulating neutrophils from patients with early breast cancer have distinct subtype-dependent phenotypes.

PURPOSE: An elevated number of circulating neutrophils is a poor prognostic factor for breast cancer, where evidence of bone marrow cancer-dependent priming is found. However, how early this priming is detectable remains unclear. PATIENTS AND METHODS: Here, we investigate changes in circulating neutrophils from newly diagnosed breast cancer patients before any therapeutic interventions. To do this, we assessed their lifespan and their broader intracellular kinase network activation states by using the Pamgene Kinome assay which measures the activity of neutrophil kinases. RESULTS: We found sub-type specific L-selectin (CD62L) changes in circulating neutrophils as well as perturbations in their overall global kinase activity. Strikingly, breast cancer patients of different subtypes (HR+, HER2+, triple negative) exhibited distinct neutrophil kinase activity patterns indicating that quantifiable perturbations can be detected in circulating neutrophils from early breast cancer patients, that are sensitive to both hormonal and HER-2 status. We also detected an increase in neutrophils lifespan in cancer patients, independently of tumour subtype. CONCLUSIONS: Our results suggest that the tumour-specific kinase activation patterns in circulating neutrophils may be used in conjunction with other markers to identify patients with cancer from those harbouring only benign lesions of the breast. Given the important role neutrophil in breast cancer progression, the significance of this sub-type of specific priming warrants further investigation.

Mapping genetic vulnerabilities reveals BTK as a novel therapeutic target in oesophageal cancer.

OBJECTIVE: Oesophageal cancer is the seventh most common cause of cancer-related death worldwide. Disease relapse is frequent and treatment options are limited. DESIGN: To identify new biomarker-defined therapeutic approaches for patients with oesophageal cancer, we integrated the genomic profiles of 17 oesophageal tumour-derived cell lines with drug sensitivity data from small molecule inhibitor profiling, identifying drug sensitivity effects associated with cancer driver gene alterations. We also interrogated recently described RNA interference screen data for these tumour cell lines to identify candidate genetic dependencies or vulnerabilities that could be exploited as therapeutic targets. RESULTS: By integrating the genomic features of oesophageal tumour cell lines with siRNA and drug screening data, we identified a series of candidate targets in oesophageal cancer, including a sensitivity to inhibition of the kinase BTK in MYC amplified oesophageal tumour cell lines. We found that this genetic dependency could be elicited with the clinical BTK/ERBB2 kinase inhibitor, ibrutinib. In both MYC and ERBB2 amplified tumour cells, ibrutinib downregulated ERK-mediated signal transduction, cMYC Ser-62 phosphorylation and levels of MYC protein, and elicited G1 cell cycle arrest and apoptosis, suggesting that this drug could be used to treat biomarker-selected groups of patients with oesophageal cancer. CONCLUSIONS: BTK represents a novel candidate therapeutic target in oesophageal cancer that can be targeted with ibrutinib. On the basis of this work, a proof-of-concept phase II clinical trial evaluating the efficacy of ibrutinib in patients with MYC and/or ERBB2 amplified advanced oesophageal cancer is currently underway (NCT02884453). TRIAL REGISTRATION NUMBER: NCT02884453; Pre-results.

An Overview of Teaching Communication of Bad News in Medical School: Should a Lecture be Adequate to Address the Topic?

INTRODUCTION: Delivering bad news is very common in medical daily practice. Several studies have shown a lack of effective communication skills amongst medical students, particularly concerning how to deliver bad news. The SPIKES protocol allows communicating bad news in a 6-step method. The aim of this study is to investigate the perspective of students related to this subject. MATERIAL AND METHODS: A 45 minute lecture "Breaking Bad News" was given to 160 students in the fifth and sixth years of the Medicine course, using the SPIKES' protocol training. After the lecture, an online survey was given to all students, and a cross-sectional and descriptive analysis of data extracted from survey was undertaken. RESULTS: Fifty-four students (21% of overall) answered the online survey. Eighty three percent said that theme should have an important role in their further daily medical practice, and most of students rated the physicians' role as challenging. Sixty percent of students expressed that communicating bad news was an integral part of the medical course curriculum. Regarding the SPIKES´ protocol, 48% felt that the first step would be the easiest to put in practice, and 40% felt that the fifth step related to "Emotions" would be the most difficult. DISCUSSION: In general, the students would like to gain competencies in breaking bad news using a practical approach Conclusions: Students highly valued theoretical and practical approaches in teaching of communication of bad news. Therefore, we encourage a combination approach in pre-graduate medical education.

Introdução: A comunicação de más notícias é muito comum na prática médica diária. Vários estudos têm demonstrado um défice de competências por parte dos estudantes de medicina quanto à forma de dar más notícias. Com a aplicação do protocolo SPIKES torna-se possível adquirir treino de competências relacionadas com tal questão em seis etapas. O objetivo deste estudo é investigar a perspetiva dos estudantes sobre o problema. Material e Métodos: Uma palestra de 45 minutos sobre "Comunicação de Más Notícias" visou os 160 estudantes do quinto e sexto ano de Medicina, usando o treino segundo protocolo de SPIKES. Após a palestra, foi implementado um inquérito online a todos os alunos, e foi realizada uma análise transversal e descritiva dos dados extraídos da pesquisa. Resultados: Cinquenta e quatro alunos (21% do total) responderam ao questionário online. Oitenta e três por cento afirmaram que o tema deverá ter um papel importante na sua futura prática médica diária, e a maioria dos estudantes avaliou o papel dos médicos como desafiante. Sessenta por cento dos estudantes expressaram que comunicar más notícias fez parte integrante do currículo do curso de medicina. Em relação ao protocolo de SPIKES, 48% sentiram que o primeiro passo seria o mais fácil de colocar em prática, e 40% sentiram que o quinto passo relacionado com as "Emoções" seria o mais difícil. Discussão: Em geral, os alunos gostariam de se sentir capacitados para obter competências nas más notícias usando uma abordagem prática. Conclusões: Os estudantes valorizam as abordagens teóricas e práticas no ensino da comunicação de más notícias. Deste modo, recomenda-se um modelo pedagógico combinado na educação médica pré-graduada.

Intussusception in gestational choriocarcinoma (not histologically proven), resolving spontaneously with chemotherapy.

We present a rare case of advanced gestational choriocarcinoma with small bowel metastatic involvement and intussusception, which presented acutely as a lower gastrointestinal bleed with symptomatic anaemia and haemoglobin 3.8 g/dL in a young woman. A diagnosis of gestational choriocarcinoma was made without biopsy, using a combination of clinical history, isolated elevated human chorionic gonadotropin markers of 77,000 IU/mL and radiological findings. Surgical intervention was too high risk due to the presence of active bleeding and increased vascularity surrounding the intussusception. Owing to the highly responsive nature of gestational choriocarcinoma to chemotherapy, frontline chemotherapy alone was used to reduce the size of the metastatic small bowel deposits, with subsequent resolution of the bleeding and intussusception. This is the first time chemotherapy alone has been used to successfully resolve small bowel intussusception secondary to metastatic choriocarcinoma that has been documented according to PubMed searches.