Activating mutations in PIK3CA, the gene encoding phosphoinositide-(3)-kinase α (PI3Kα), are frequently found in estrogen receptor (ER)–positive breast cancer. PI3Kα inhibitors, now in late-stage clinical development, elicit a robust compensatory increase in ER-dependent transcription that limits therapeutic efficacy. We investigated the chromatin-based mechanisms leading to the activation of ER upon PI3Kα inhibition. We found that PI3Kα inhibition mediates an open chromatin state at the ER target loci in breast cancer models and clinical samples. KMT2D, a histone H3 lysine 4 methyltransferase, is required for FOXA1, PBX1, and ER recruitment and activation. AKT binds and phosphorylates KMT2D, attenuating methyltransferase activity and ER function, whereas PI3Kα inhibition enhances KMT2D activity. These findings uncover a mechanism that controls the activation of ER by the posttranslational modification of epigenetic regulators, providing a rationale for epigenetic therapy in ER-positive breast cancer.

assisted with the initial computational analyses. H.Z. helped with the mouse in vivo experiment. K.J. assisted with patient selection. P.R. performed the nested control study, and assisted with patient sample procurement and survival analyses. P.R. and C.S. also performed the patient clinical annotation. J.S.R. viewed the FFPE slides, performed the laser microdissection and provided intellectual support. C.K. supervised the SWI/SNF complex ChIP-seq, helped with the SWI/SNF complex ChIP-seq data interpretation and provided intellectual insights.

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Background Advance care planning (ACP) is the process of ongoing communication among patients, family and health care professionals regarding what plans for future care are preferred in the event that patients become unable to make their own decisions. Clinicians play an important role in ACP as both initiators and decision coaches. However, lack of training for clinicians has frequently been reported as the reason for low involvement in ACP discussions - hence the present review evaluates the effectiveness of ACP training programs for healthcare professionals to guide the development of novel training programs for them in the future. Methods A literature search for intervention studies was conducted independently by two reviewers in July 2018. Participants included all healthcare professionals working with adult patients suffering from terminal illness. The primary outcomes were the professionals’ knowledge of and attitudes towards ACP, and self-perceived competence in ACP conversations. The Effective Public Health Practice Project appraisal tool was used to examine the quality of the studies included. Results A total of 4025 articles were identified, and ten eligible articles, covering 1081 participants, were included in the review. However, there is a lack of high quality randomized controlled trials of providing ACP training for nurses working in non-palliative care hospital settings. The overall quality of the intervention studies was moderate. All the studies included used instructional sessions in their interventions, while some contained group discussion, role-play and the use of advanced technology. The training programs increased the knowledge, attitudes towards shared decision-making, perceived communication skills, confidence, comfort and experiences concerned with discussing end-of-life (EOL) issues. Patient advocacy, job satisfaction and perceived level of adequate training for EOL care were improved. The use of ‘decision aids’ was rated as acceptable and clinically useful. Conclusions Training for healthcare professionals in ACP has positive effects on their knowledge, attitude and skills. The use of decision aids and advanced technology, instructional sessions with role play, training content focused on ACP communication skills and the needs and experience of patient in the ACP process, and a values-based ACP process are all those factors that made the ACP training programs effective.

Background Peripheral intravenous cannulation (PIC) is commonly performed in cancer treatment and causes pain and anxiety to children with cancer. Objective The aim of this study was to determine whether virtual reality distraction intervention can alleviate pain and anxiety and reduce length of procedure among pediatric cancer patients undergoing PIC. Methods One hundred eight pediatric cancer patients aged 6 to 17 years were recruited from a regional public hospital in Hong Kong to participate in this randomized controlled trial. The intervention group received virtual reality distraction intervention, and the control group received standard care. The primary outcome was child-reported pain. Secondary outcomes included child-reported anxiety, pulse rate, and length of procedure. Outcome measurements were conducted at 5 minutes before, during, and immediately after the procedure. Results Pediatric cancer patients in the intervention group demonstrated a significantly greater reduction in pain (estimated mean difference = −1.69, P = .007) and anxiety levels (estimated mean difference = −3.50, P < .001) compared with the control group. The mean duration (in minutes) for the PIC procedure was significantly shorter among participants receiving virtual reality intervention compared with the control counterparts (estimated mean difference = −0.75, P = .017). However, no significant difference was observed in pulse rate during and after the procedure between groups. Conclusions Findings indicate that virtual reality is safe and effective to alleviate pain and anxiety among pediatric cancer patients undergoing PIC procedure. Implications for Practice Virtual reality can be considered as an adjunctive treatment to manage pain and anxiety in pediatric cancer patients before and during PIC procedure.