Background HER2-low breast cancer (BC) is currently an area of active interest. This study evaluated the impact of low expression of HER2 on survival outcomes in HER2-negative non-metastatic breast cancer (BC). Methods Patients with HER2-negative non-metastatic BC from 6 centres within the Asian Breast Cancer Cooperative Group (ABCCG) (n = 28,280) were analysed. HER2-low was defined as immunohistochemistry (IHC) 1+ or 2+ and in situ hybridization non-amplified (ISH−) and HER2-zero as IHC 0. Relapse-free survival (RFS) and overall survival (OS) by hormone receptor status and HER2 IHC 0, 1+ and 2+ ISH− status were the main outcomes. A combined TCGA-BRCA and METABRIC cohort (n = 1967) was also analysed to explore the association between HER2 expression, ERBB2 copy number variation (CNV) status and RFS. Results ABCCG cohort median follow-up was 6.6 years; there were 12,260 (43.4%) HER2-low BC and 16,020 (56.6%) HER2-zero BC. The outcomes were better in HER2-low BC than in HER2-zero BC (RFS: centre-adjusted hazard ratio (HR) 0.88, 95% CI 0.82–0.93, P < 0.001; OS: centre-adjusted HR 0.82, 95% CI 0.76–0.89, P < 0.001). On multivariable analysis, HER2-low status was prognostic (RFS: HR 0.90, 95% CI 0.85–0.96, P = 0.002; OS: HR 0.86, 95% CI 0.79–0.93, P < 0.001). These differences remained significant in hormone receptor-positive tumours and for OS in hormone receptor-negative tumours. Superior outcomes were observed for HER2 IHC1+ BC versus HER2-zero BC (RFS: HR 0.89, 95% CI 0.83–0.96, P = 0.001; OS: HR 0.85, 95% CI 0.78–0.93, P = 0.001). No significant differences were seen between HER2 IHC2+ ISH− and HER2-zero BCs. In the TCGA-BRCA and METABRIC cohorts, ERBB2 CNV status was an independent RFS prognostic factor (neutral versus non-neutral HR 0.71, 95% CI 0.59–0.86, P < 0.001); no differences in RFS by ERBB2 mRNA expression levels were found. Conclusions HER2-low BC had a superior prognosis compared to HER2-zero BC in the non-metastatic setting, though absolute differences were modest and driven by HER2 IHC 1+ BC. ERBB2 CNV merits further investigation in HER2-negative BC.

Breast metastases from non-breast primaries are rare in female patients and exceedingly rare in male patients, with only a handful of cases described. Lymphoma, metastatic melanoma and bronchial carcinoma are the primary sites for the majority of breast metastases. Breast metastases from colorectal carcinoma have been described previously in only a small number of cases in the literature. Here, we report a further two patients with biopsy-proven colorectal carcinoma metastases to both breasts, who demonstrate contrasting unusual and atypical imaging features that have not been reported previously. In one case, the imaging appearances mimic a multifocal primary breast carcinoma. Metastatic disease in the breast is a marker for disseminated metastatic spread, with a correspondingly poor prognosis. Therefore, we review the imaging features that differentiate metastatic breast disease from multifocal breast primaries, which are important to recognize because the management options for these patients differ greatly.

Background: Heralded as a teaching, assessment and reflective tool, and increasingly as a longitudinal and holistic perspective of the educator’s development, medical educator’s portfolios (MEP)s are increasingly employed to evaluate progress, assess for promotions and career switches, used as a reflective tool and as a means of curating educational activities. However, despite its blossoming role, there is significant dissonance in the content and structure of MEPs. As such, a systematic scoping review (SSR) is proposed to identify what is known of MEPs and its contents. Methods: Krishna’s Systematic Evidenced Based Approach (SEBA) was adopted to structure this SSR in SEBA of MEPs. SEBA’s constructivist approach and relativist lens allow data from a variety of sources to be considered to paint a holistic picture of available information on MEPs. Results: From the 12 360 abstracts reviewed, 768 full text articles were evaluated, and 79 articles were included. Concurrent thematic and content analysis revealed similar themes and categories including: (1) Definition and Functions of MEPs, (2) Implementing and Assessing MEPs, (3) Strengths and limitations of MEPs and (4) electronic MEPs. Discussion: This SSR in SEBA proffers a novel 5-staged evidence-based approach to constructing MEPs which allows for consistent application and assessment of MEPs. This 5-stage approach pivots on assessing and verifying the achievement of developmental milestones or ‘micro-competencies’ that facilitate micro-credentialling and effective evaluation of a medical educator’s development and entrust-ability. This allows MEPs to be used as a reflective and collaborative tool and a basis for career planning.

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Objectives: To develop a paediatric radiology themed escape room session for undergraduate education and secondly, to determine participant satisfaction and improvement in knowledge. Methods: A paediatric radiology escape room with accompanying tutorial was developed around key learning objectives set within the RCR and ESR undergraduate curriculum. Students were recruited from two different universities and undertook the escape room themed teaching. An 8-question single best answer (SBA) test was completed before, immediately after and at 2 weeks post-teaching to determine participant improvement and retention of knowledge. The general feedback was also collected. Results: The escape room sessions were held three times, for 19 students (6-7 students per session). All groups completed the escape room in ≤ 20 min. Students enjoyed the experience, assigning an average satisfaction score of 9.4/10 (range 7-10). The majority (17/19, 89.5%) preferred this method of teaching to a lecture-based tutorial alone, although all said they found the tutorial component useful. For the SBA test, there was an average increase in 3.6 marks (range 1-6 marks) per participant between before and after the escape room. This improved knowledge was mostly sustained after 2 weeks, with an average increase of 3.4 marks difference (range 1 to 6) per participant compared to before the teaching. Conclusions: A paediatric radiology themed escape room is a feasible teaching method, enjoyed by participants and associated with an increase in radiological knowledge. Further work with larger sample size and direct comparison with other traditional teaching methods is required.A paediatric radiology themed escape room is a feasible teaching method. Students enjoyed the escape room, and most preferred it over didactic lectures. Improvement in paediatric radiology knowledge was maintained after the teaching.

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Background & Aims Most patients develop recurrent disease despite curative surgery for hepatocellular carcinoma (HCC). No standard adjuvant therapy is available and molecular predictors of outcome are poorly understood. Methods We conducted a multicentre pilot study on patients with localized HCC following surgical resection. Patients received up to 6 months of oral gefitinib as adjuvant therapy. Clinical end points included recurrence‐free survival (RFS) and overall survival (OS), and exploratory analyses were conducted from whole exome sequencing data. Results A total of 65 patients were screened for the study, of which 40 were eligible. The median age was 63 years (range, 44‐80). Most patients (80%) were positive for hepatitis B or C. With a median follow‐up of 4.5 years, the median RFS was 24 months. Median OS was not reached. High Child‐Pugh score and advanced T‐stage (3‐4) were independent predictors for both OS and RFS. Mutational signatures for exposure to aristolochic acid (AA), as characterized by a majority of T:A > A:T mutations, were observed in 18 cases (55%). HCC without AA mutagenesis was associated with early recurrences or death within 2 years of surgery (P = .037). HCC with high T > A mutations was associated with better OS (HR 0.29, 95% CI 0.09‐0.90, P = .033). Conversely, HCC with high C > T mutations was associated with worse OS (HR 4.55, 95% CI 1.20‐17.31, P = .026). Conclusions Mutational signatures may carry prognostic significance in HCC following curative resection. Patient outcomes with gefitinib as adjuvant therapy after resection for HCC were modest, highlighting the need for urgent research in this area of unmet clinical need. http://ClinicalTrials.gov number, NCT00282100.

Background/Aim: Acral melanomas (AM) represent a rare subgroup of melanomas with poor clinical outcomes and are enriched in Asian populations. Recent advances in next generation sequencing have provided opportunities to apply precision medicine to AM. Patients and Methods: Here, we present a series of 13 patients with melanomas from Taiwan and Singapore, including 8 patients with AM profiled using whole exome sequencing and summarize the recent studies on the genomic landscape of AM. Results: We identified mutually exclusive mutations in BRAF, NRAS, HRAS, NF1 and KIT in 6 AM cases. In addition, recurrent copy number gains in CCND1 and CDK4, as well as recurrent deletions in CDKN2A/CDKN2B, ATM and RAD51 were observed, supporting the potential use of CDK4/6 or PARP inhibitors in the treatment of these patients. Conclusion: The genomic landscape of AM provides an important resource for applying novel targeted therapies in this rare disease.Acral melanomas (AM) are a subset of melanomas that arise from non-hair bearing glabrous skin on the palms and soles, or on the nail apparatus (1). Despite global rarity, AM is the commonest subtype of melanoma in Asian populations (2). Notably, patients with AM harbor worse prognosis as compared with cutaneous melanomas, and survival outcomes remain dismal despite modern advances in the therapeutic landscape of melanomas (3,4).Recently, next generation sequencing (NGS) technologies, involving whole exome (WES) (5-7) or genome sequencing (WGS) (8-14), have enhanced the molecular understanding of AM. At the molecular level, AM is a distinct disease as compared with cutaneous melanomas, defined by few point or indel mutations and high degrees of complex structural rearrangements and focal copy number alterations (8-10). Unlike cutaneous melanomas, the tumor mutation burden (TMB) is consequently lower and mutational signatures of ultraviolet damage are infrequent (11). At the individual gene level, hotspot mutations in BRAF and NRAS occur in over 50% of cutaneous melanomas, whereas their occurrence in AM is considerably lower (approximately 10-25%). On the other hand, mutations in NF1 and KIT, as well as oncogenic amplification of genes such as CCND1, CDK4, and TERT have been demonstrated to be common events in AM (5, 8). These unique genomic alterations harbor therapeutic implications -small molecule inhibitors of KIT and other tyrosine kinases, including imatinib, nilotinib and dasatinib, have demonstrated significant (albeit modest) efficacy against . Similarly, CDK4/6 inhibitors have also shown promising activity in AM (19). Taken together, the unique genomic landscape of AM offers an opportunity for the application of precision medicine in this rare disease and warrants further investigation.In this article, we present a series of patients with AM from Taiwan and Singapore profiled using whole exome sequencing and summarize the recent studies on the genomic landscape of AM using NGS, extending our current understanding of this Asian-prevalent subtype of melanoma.