Transitions Pop-ups: Co-designing client-centred support for disabled youth transitioning to adult life.

Background: When transitioning to adulthood, youth with disabilities and their families face many service gaps. Successful inter-agency collaborations can promote family-centred, inclusive transition support amenable to personal choice and health conditions. This paper reports the 3-year co-design process of an innovative transition service that links a pediatric hospital and adult service agencies and addresses key areas of transition preparedness with joint accountability. Methods: A team of pediatric rehabilitation professionals, adult service providers, young adults with disabilities and their families, and researchers engaged in a co-design process over three years. Following a design thinking (DT) framework, the team went through an iterative process of Empathize. Define, Ideation, Prototyping, and Testing phases. The trial-and-error process allowed for deeper reflection and an opportunity to pivot the design. Results: The co-design yielded Transitions Pop-ups, a nimble service model that can "pop up" at critical times and places to meet clients' urgent and emergent transition-related needs. Two pilot sessions were conducted at the testing phase with adult service agencies. The final model included five key elements: (1) community partnership; (2) targeted information sharing; (3) peer mentoring; (4) action (on-the-spot completion of a key transition task/activity such as submitting an adult funding application); and (5) warm handover. Conclusion: The co-design process highlighted the importance of open communication and iterative prototype testing as a means for trialing new ideas and clarifying the intent of the project. The DT framework optimally facilitated the co-development of a contextually relevant and sustainable service model for pediatric rehabilitation clients and families.

Facilitating virtual social connections for youth with disabilities: lessons for post-COVID-19 programming.

PURPOSE: Social connections are essential for the development of life skills for youth. Youth with disabilities have long faced barriers to meaningful social connections. The onset of COVID-19 increased barriers to social connections for all youth, and also led to enhanced use of virtual platforms in paediatric rehabilitation programming. Harnessing this opportunity, service providers created a suite of online programs to foster social connections and friendships. The current study explores participant and service provider experiences of such programs. METHODS: This qualitative descriptive study used interviews and focus groups to explore how youth with disabilities (n = 8), their parents (n = 7), and service providers (n = 13) involved in program development and delivery experienced the programs, the accessibility of the virtual platforms, and their social connections in relation to program participation. RESULTS: Participants were satisfied with the programs' content, accessibility and ability to meet their social needs. Qualitative themes included facilitating social connections, accessibility of virtual spaces, and recommendations for future virtual programming. DISCUSSION: For youth with disabilities who have been historically marginalized in social spheres, the newly ubiquitous infrastructure regarding virtual programming must be supported and enhanced. A hybrid approach involving virtual/in-person options in future programming is recommended.

Youth with disabilities can benefit from social connections on virtual platforms in terms of physical access to social spaces and opportunities to communicate in alternative waysFor some youth with disabilities, virtual social connections can be the only feasible and readily available option for reducing social isolation due to physical barriers to accessWhen offering virtual program options, service providers should consider the various benefits of connecting with the physical, communication-based, interaction-based, access-based and other barriers to virtual connection.

A Case Study Implementing a Social Needs Screening Process and a Family Navigation Hub at Holland Bloorview Kids Rehabilitation Hospital.

Identifying and addressing clients' and families' most pressing social determinants of health needs are integral to quality healthcare. Healthcare leaders and front-line clinicians have long recognized the connection between unmet essential resource needs, such as food, housing and transportation and health outcomes. As a component of broader organizational efforts to improve equitable access to services, a social needs screening (SNS) initiative was introduced, along with a Family Navigation Hub providing navigation interventions. This paper describes the systematic approach taken to support the SNS initiative implementation and highlights evaluation results of the first year of activity.

The creation and implementation of an employment participation pathway model for youth with disabilities.

PURPOSE: Employment participation offers benefits including income, sense of accomplishment, social engagement, and meaningful contribution to society. Rates of competitive employment of youth with disabilities are amongst the lowest in society, despite having capacity and motivation to participate in the workplace. The marginalization of young workers with disability presents a lost opportunity for youth, potential employers, and social care systems. In order to engage young people with disabilities in employment, we present an integrated, community-based model for employment participation preparation. MATERIALS AND METHODS: The employment participation pathway model is based on best available evidence and 15 years of program delivery for youth with disabilities preparing to transition out of school and into employment in the Canadian context. It was conceptualized using the Knowledge to Action framework and presented for consideration in the current paper. RESULTS: Starting early, taking a person-directed approach to planning, and considering the individual and our systems contribute to effective and comprehensive transition to employment. CONCLUSIONS: The employment participation model provides evidence and examples for service providers to consider integrating into their repertoire and begin to construct similar pathways to equip their clients and families with skills, capacities, and knowledge as they journey towards workplace participation.IMPLICATIONS FOR REHABILITATIONEmployment for individuals with disabilities is lower than the national average, with rates being even lower for young people (ages 15-25) with disabilities.Low workplace participation for individuals with disabilities is particularly troubling due to the myriad social and health benefits of engagement in employment.Programs that start early (during high school) and provide ongoing, community-integrated support are reported to be most beneficial to the eventual job attainment and retention for young job seekers with disabilities.The presented employment participation pathway model that was developed using the Knowledge to Action Framework integrates evidence and best practices to support service providers in facilitating progressive workplace participation for clients and families.

Putting Youth in Charge: Exploring a Multi-Year Interagency Community Engagement Experiential Programme for Youth with Disabilities and Their Families.

This paper outlines a qualitative exploration of the experiences of Youth in Charge (YiC), a 3-year pilot programme. YiC was designed to promote early, immersive community participation for students with physical disabilities, and was co-developed/co-hosted by three agencies (hospital, community rehabilitation, school board). To better understand the experiences of the youth, parents, and staff involved in this broad intervention, observation of 10 programme sessions and annual semi-structured interviews with youth (n = 5), parents (n = 4) and staff (n = 6) were undertaken. Qualitative results comprise six themes based in the two major thematic areas of participation-related experiences and programme considerations. Results indicate the need for community-based experiences, measured risk-taking, long-term engagement, parental involvement, and greater interagency collaboration and integration.

A case study of a strategic initiative in pediatric rehabilitation transition services: An insiders' perspective on team principles and practices.

Aims: The aim was to describe an innovative initiative that took place in a pediatric rehabilitation hospital. The goal of this organization-wide strategic initiative, called the Transition Strategy, was to improve service delivery to children/youth with disabilities and their families at times of life transition. The research question was: What are the key elements that have contributed to the success of the Strategy, from the perspective of team members? The objectives were to describe: (a) the guiding principles underlying team functioning and team practices, (b) key enablers of positive team functioning, (c) the nature of effective team practices, and (d) lessons learned. Methods: A holistic descriptive case study was conducted, utilizing historical documents, tracked outcome data, and the experiences and insights of multidisciplinary team members (the authors). Reflecting an insiders' perspective, the impressions of team members were key sources of data. The perspectives of team members were used to generate key teamwork principles, enablers of team functioning, team practices, and key learnings. Findings and Discussion: Team members identified four guiding humanistic principles (respect, support, partnership, and open communication). These principles underpinned three novel practices that contributed to team effectiveness in the eyes of team members: supportive relational practices, human-centered co-design, and solution-focused communication. Key enablers were the relational style of leadership, and a team climate of innovation, autonomy, and trust, supported by the organizational vision. This team climate fostered a sense of psychological safety, thereby encouraging both experimentation and learning from failure. Conclusions: This article provides information for other healthcare organizations interested in understanding the Strategy's value and its implementation. It provides a practical example of how to adopt a humanistic approach to health care, leading to both innovative service development and thriving among team members.

Transitions Theatre: Creating a Research-Based Reader's Theatre With Disabled Youth and Their Families.

Transition to adult life can be a challenging time for disabled youth and their families. This article describes the collaborative creation of Transitions Theatre, a research-based reader's theatre activity based on narrative interviews with eight disabled youth (aged 17-22) and seven parents. Analysis of these interviews generated two opposing yet interrelated themes. On one hand, youth and families felt lost in transition facing multiple gaps in healthcare, financial support, education, and opportunities for social participation after having "aged out" of the pediatric system. On the other hand, they started cripping "normal" adulthood to envision more inclusive futures wherein disabilities are understood as integral to society. These two themes were transformed into two reader's theatre scripts, one featuring a youth, the other featuring a parent. Seven youth and four parents (six of them were original interview participants) then participated in a Transitions Theatre workshop to read the scripts together and discuss the authenticity and relatability of the scripts. Participant feedback suggested that the reader's theatre method was effective in sharing findings with research participants and stimulating a critical dialogue on how to (re)imagine transition to adulthood. We discuss the importance of implementing inclusive design strategies to make reader's theatre accessible to participants with diverse abilities and preferences.

Transitions Theatre: An Arts-Informed Interprofessional Education Workshop.

Introduction: Transition from pediatric to adult care has significant implications for health outcomes in youth with special health care needs. To optimally support the transition, health care and social service providers must work collaboratively with youth and families in service planning, implementation, and evaluation. Based on interviews with 15 youth and their families, we developed an arts-informed interprofessional education activity titled Transitions Theatre using the method of readers' theater. Methods: Three educators with lived experience (one former pediatric rehabilitation client and two parents of youth with special health care needs) and three academic/clinical educators codesigned the transitions. We conducted four online workshops (14-20 participants each). Results: A total of 67 people participated: 59 students from 11 health disciplines and seven postlicensure clinicians and one trainee from five disciplines (e.g., occupational therapy, life skills coaching, early childhood education). Twenty-six participants answered both pre- and postworkshop surveys and reported a positive shift in their understanding of client and family perspectives, their roles in transition support, and other providers' roles in transition support. After the workshop, learners felt more confident with transition support and interprofessional collaboration. The perspectives of the educators with lived experience aligned with the theater scripts and enhanced learners' empathetic engagement with the topic. Discussion: The evidence-based teaching approach of readers' theater and our coteaching model offered learners a unique opportunity to learn about the challenges clients and their families face at the time of transition to adulthood and identify their role in an interprofessional transition support.

Oncology clinical trial disruption during the COVID-19 pandemic: a COVID-19 and cancer outcomes study.

BACKGROUND: COVID-19 disproportionately impacted patients with cancer as a result of direct infection, and delays in diagnosis and therapy. Oncological clinical trials are resource-intensive endeavors that could be particularly susceptible to disruption by the pandemic, but few studies have evaluated the impact of the pandemic on clinical trial conduct. PATIENTS AND METHODS: This prospective, multicenter study assesses the impact of the pandemic on therapeutic clinical trials at two large academic centers in the Northeastern United States between December 2019 and June 2021. The primary objective was to assess the enrollment on, accrual to, and activation of oncology therapeutic clinical trials during the pandemic using an institution-wide cohort of (i) new patient accruals to oncological trials, (ii) a manually curated cohort of patients with cancer, and (ii) a dataset of new trial activations. RESULTS: The institution-wide cohort included 4756 new patients enrolled to clinical trials from December 2019 to June 2021. A major decrease in the numbers of new patient accruals (-46%) was seen early in the pandemic, followed by a progressive recovery and return to higher-than-normal levels (+2.6%). A similar pattern (from -23.6% to +30.4%) was observed among 467 newly activated trials from June 2019 to June 2021. A more pronounced decline in new accruals was seen among academically sponsored trials (versus industry sponsored trials) (P < 0.05). In the manually curated cohort, which included 2361 patients with cancer, non-white patients tended to be more likely taken off trial in the early pandemic period (adjusted odds ratio: 2.60; 95% confidence interval 1.00-6.63), and substantial pandemic-related deviations were recorded. CONCLUSIONS: Substantial disruptions in clinical trial activities were observed early during the pandemic, with a gradual recovery during ensuing time periods, both from an enrollment and an activation standpoint. The observed decline was more prominent among academically sponsored trials, and racial disparities were seen among people taken off trial.

Integrating lived experience into clinical practice: a case study of young peer providers in pediatric rehabilitation.

PURPOSE: Youth Facilitators (YFs) are peer service providers (SPs) with childhood-onset disabilities working in pediatric rehabilitation teams. This study explored the YF role focusing on what work YFs do, the perceived facilitators and challenges pertinent to the role integration process, and the evolution of the role over the study period. METHODS: A longitudinal, qualitative case study approach was used to gather data over a total period of 14 months through interviews, focus groups, workload logs, and observations. Data were analyzed using the method of thematic analysis. RESULTS: Two YFs, 23 SPs and two managers participated in the study. YFs' work included independent consultation, resource provision, referral making, and program co-facilitation. Analysis produced two contrasting themes. When viewed as a representative of clients, YFs were considered bringing client perspectives to care, adding credibility to clinical services, and empowering clients and families through role modeling. However, when viewed as a professional SP, their expertise was questioned due to role unclarity, limited generalizability of lived experience, and organizational limitations. CONCLUSIONS: Training tailored to local care contexts and organizational supports are needed to transform YFs' experiential knowledge into experiential expertise. We propose strategies for optimal integration of peer providers into clinical care teams.Implications for rehabilitationAs peer service providers with lived experience of disabilities, Youth Facilitators (YFs) have the potential to benefit pediatric rehabilitation services by facilitating empowerment in clients and families as they navigate through life transitions.The YF scope of practice and training should be adapted to fit with individual clinical teams and local care contexts to help YFs establish their experiential expertise in interdisciplinary teams.Establishing YF's core competencies (e.g., advocacy, coaching, and boundary setting skills) can help transform their experiential knowledge into experiential expertise.

Prioritizing a Research Agenda of Transitional Care Interventions for Childhood-Onset Disabilities.

Transitional care interventions have the potential to optimize continuity of care, improve health outcomes and enhance quality of life for adolescents and young adults living with chronic childhood-onset disabilities, including neurodevelopmental disorders, as they transition to adult health and social care services. The paucity of research in this area poses challenges in identifying and implementing interventions for research, evaluation and implementation. The purpose of this project was to advance this research agenda by identifying the transitional care interventions from the scientific literature and prioritize interventions for study. A modified-Delphi approach involving two rounds of online surveys followed by a face-to-face consensus meeting with knowledge users, researchers and clinician experts in transitional care (n = 19) was used. A subsequent virtual meeting concluded the formulation of next steps. Experts rated 16 categories of interventions, derived from a systematic review, on importance, impact, and feasibility. Seven of the 16 interventions categories received a mean score rating of ≥7 (out of 10) on all three rating categories. Participants then rank ordered the reduced list of seven interventions in order of priority and the top four ranked interventions advanced for further discussion at a consensus meeting. Using the Template for Intervention Description and Replication (TIDieR) checklist as a guide, the participants identified that a study of a peer system navigator was worthy of future evaluation. This study highlighted that transitional care interventions are complex and multifaceted. However, the presence of a peer to support system navigation, advocacy and individual and family education was considered the most ideal intervention addressing the current gap in care. Future research, which aims to engage patients and families in a co-design approach, is recommended to further develop this intervention.

An economic analysis comparing health care resource use and cost of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin versus gemcitabine and cisplatin as neoadjuvant therapy for muscle invasive bladder cancer.

PURPOSE: To compare healthcare resource utilization (HRU) and costs associated with dose-dense methotrexate, vinblastine, doxorubicin, cisplatin (ddMVAC) and gemcitabine, cisplatin (GC) as neoadjuvant chemotherapy for muscle-invasive bladder cancer (MIBC). METHODS: Patient treated at Dana-Farber Cancer Institute from 2010 to 2019 were identified. HRU data on chemotherapy administered, supportive medications, patient monitoring, clinic, infusion, emergency department (ED) visits and hospitalization were collected retrospectively. Unit costs for HRU components were obtained from the Centers for Medicare and Medicaid Website and HRU was compared between groups using quantile regression analysis. RESULTS: 137 patients were included; 51 received ddMVAC and 86 GC. Baseline characteristics were similar, except lower mean age (P < 0.001) and higher proportion of ECOG-PS = 0 (P < 0.001) for ddMVAC. ddMVAC required more granulocyte-colony stimulating factor support (P < 0.001), central line placement (P = 0.017), cardiac imaging (P < 0.001), and infusion visits (P < 0.001), whereas GC required more clinic visits. ED visits were higher for ddMVAC (P = 0.048), while chemotherapy cycle delays and hospitalization days were higher for GC (P = 0.008). After adjusting for ECOG-PS and age, the cost per patient was approximately 41% lower (95%CI: 28% to 52%; P < 0.001) for GC vs. ddMVAC, which translated to a median adjusted cost savings of $7,410 (95%CI: $5,474-$9,347) per patient. CONCLUSIONS: Although excess HRU did not clearly favor one regimen, adjusting for PS and age indicated lower costs with GC vs. ddMVAC. Given the similar cumulative cisplatin delivery with both regimens, the associated values and costs supports the preferential selection of GC in the neoadjuvant setting of MIBC.

Association of clinical factors and recent anticancer therapy with COVID-19 severity among patients with cancer: a report from the COVID-19 and Cancer Consortium.

BACKGROUND: Patients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies. PATIENTS AND METHODS: Patients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). Multivariable regression models included demographics, cancer status, anticancer therapy and timing, COVID-19-directed therapies, and laboratory measurements (among hospitalized patients). RESULTS: A total of 4966 patients were included (median age 66 years, 51% female, 50% non-Hispanic white); 2872 (58%) were hospitalized and 695 (14%) died; 61% had cancer that was present, diagnosed, or treated within the year prior to COVID-19 diagnosis. Older age, male sex, obesity, cardiovascular and pulmonary comorbidities, renal disease, diabetes mellitus, non-Hispanic black race, Hispanic ethnicity, worse Eastern Cooperative Oncology Group performance status, recent cytotoxic chemotherapy, and hematologic malignancy were associated with higher COVID-19 severity. Among hospitalized patients, low or high absolute lymphocyte count; high absolute neutrophil count; low platelet count; abnormal creatinine; troponin; lactate dehydrogenase; and C-reactive protein were associated with higher COVID-19 severity. Patients diagnosed early in the COVID-19 pandemic (January-April 2020) had worse outcomes than those diagnosed later. Specific anticancer therapies (e.g. R-CHOP, platinum combined with etoposide, and DNA methyltransferase inhibitors) were associated with high 30-day all-cause mortality. CONCLUSIONS: Clinical factors (e.g. older age, hematological malignancy, recent chemotherapy) and laboratory measurements were associated with poor outcomes among patients with cancer and COVID-19. Although further studies are needed, caution may be required in utilizing particular anticancer therapies. CLINICAL TRIAL IDENTIFIER: NCT04354701.

Perceived Impacts of Solution-Focused Coaching Training for Pediatric Rehabilitation Practitioners: A Qualitative Evaluation.

AIMS: This qualitative evaluation study assessed perceived impacts of a solution-focused coaching (SFC) training rolled out in a Canadian pediatric rehabilitation hospital from the perspective of clinical service providers. METHODS: Thirteen clinical service providers were interviewed six months after receiving 2-day SFC training. Participants retrospectively described perceived impacts of the training and benefits and challenges pertinent to the implementation of the SFC approach. Interview transcripts were transcribed verbatim and analyzed thematically. RESULTS: SFC training was considered making a valuable addition to participants' toolbox, increasing their confidence in developing positive therapeutic alliance with clients, and enhancing their strengths-based orientation. The training was also seen improving team cohesion and promoting collaborative solution-finding among team members. Structural barriers such as time constraints, lack of continuous organizational support and clear expectations around the use of the SFC approach were reported as factors impeding effective clinical adaptation. The need for tailoring the SFC approach to unique service contexts was also reported. CONCLUSIONS: Future SFC training initiatives should integrate a team-based approach and a culturally sensitive lens to help providers better assist clients in identifying their unique strengths. Follow-up training and continuous organizational support mechanisms will be vital for facilitating sustainable implementation after the initial training.

Performance and visual arts-based programs for children with disabilities: a scoping review focusing on psychosocial outcomes.

Purpose: There is a growing movement in pediatric rehabilitation to understand how approaches addressing aspects beyond body function contribute to enhanced psychosocial well-being. Among such approaches is the use of creative arts. A scoping review was undertaken to synthesize the current literature on performance and visual arts-based programs and outcomes for children with disabilities.Methods: Data sources included CINAHL, MEDLINE, and PsycINFO. Eligible articles described programs involving performing or visual art activities in community and ambulatory care settings, delivered to children between 6 and 18 years with physical or developmental disabilities, and reported on at least one psychosocial outcome. Domains of interest included emotional, social, behavioral, physical, cognitive, and/or communicative functioning, which are known to impact well-being and participation. No limits were applied to study design.Results: Twelve articles using primarily case study and quasi-experimental designs were identified, encompassing an 11-year period. Most programs focused on theater as the central modality. A majority of papers addressed changes in physical, cognitive, and communicative function (n = 8), followed by social function (n = 6), emotional function (n = 5), and finally, behavioral function (n = 3). Across individual papers, diverse study designs, measures, and outcomes were examined with positive qualitative and/or quantitative findings noted across all domains.Conclusions: Within an emerging evidence base, arts-based programs show potential to positively impact psychosocial well-being and warrant further investigation with broader populations of children with physical and developmental disabilities. A greater emphasis on programmatic approaches and enhanced methodological rigor to establishing benefits is needed to advance understanding.Implications for rehabilitationPediatric therapists may wish to consider recommending arts-based programs for children with ASD, TBI, and other developmental disabilities given their potential in achieving psychosocial outcomesArts-based programs in rehabilitation provide creative ideas (e.g., drawing, painting) and techniques (e.g., modeling, role-play), which may be incorporated into individualized or group-based therapy to promote psychosocial well-beingProgram evaluators and researchers are encouraged to adopt a programmatic approach to further explore how art activities facilitate psychosocial outcomes.

Impact of Solution-Focused Coaching Training on Pediatric Rehabilitation Specialists: A longitudinal evaluation study.

Fostering successful interprofessional collaboration remains a challenge in pediatric rehabilitation. A coaching approach can enhance client-centered care and provide a transdisciplinary framework for collaboration. The purpose of this longitudinal study was to evaluate the impact of Solution-Focused Coaching in Pediatric Rehabilitation (SFC-peds) training on pediatric rehabilitation practitioners from multiple disciplinary backgrounds. Thirty-seven service providers (SPs) completed surveys at baseline and three follow-ups. Quantitative and qualitative findings both suggested that the training proved an effective way to achieve substantial and sustainable improvements in SFC knowledge, confidence, and use of SFC-peds techniques among participating SPs. The educational intervention also facilitated the integration of a strengths-based, solution-building approach at an individual and team level, providing SPs with a common language and shared framework for client-centered care and optimal collaboration with colleagues. A need for practice opportunities tailored to unique care contexts was identified. Future research should further explore the impacts of a SFC-peds approach on interprofessional teams, as well as on health outcomes of clients.

Quantifying Argonaute 2 (Ago2) expression to stratify breast cancer.

BACKGROUND: Argonaute-2 (Ago2) is an essential component of microRNA biogenesis implicated in tumourigenesis. However Ago2 expression and localisation in breast cancer remains undetermined. The aim was to define Ago2 expression (mRNA and protein) and localisation in breast cancer, and investigate associations with clinicopathological details. METHODS: Ago2 protein was stained in breast cancer cell lines and tissue microarrays (TMAs), with intensity and localization assessed. Staining intensity was correlated with clinicopathological details. Using independent databases, Ago2 mRNA expression and gene alterations in breast cancer were investigated. RESULTS: In the breast cancer TMAs, 4 distinct staining intensities were observed (Negative, Weak, Moderate, Strong), with 64.2% of samples stained weak or negatively for Ago2 protein. An association was found between strong Ago2 staining and, the Her2 positive or basal subtypes, and between Ago2 intensity and receptor status (Estrogen or Progesterone). In tumours Ago2 mRNA expression correlated with reduced relapse free survival. Conversely, Ago2 mRNA was expressed significantly lower in SK-BR-3 (HER2 positive) and BT-20 (Basal/Triple negative) cell lines. Interestingly, high levels of Ago2 gene amplification (10-27%) were observed in breast cancer across multiple patient datasets. Importantly, knowledge of Ago2 expression improves predictions of breast cancer subtype by 20%, ER status by 15.7% and PR status by 17.5%. CONCLUSIONS: Quantification of Ago2 improves the stratification of breast cancer and suggests a differential role for Ago2 in breast cancer subtypes, based on levels and cellular localisation. Further investigation of the mechanisms affecting Ago2 dysregulation will reveal insights into the molecular differences underpinning breast cancer subtypes.

Quantifying Tip60 (Kat5) stratifies breast cancer.

Breast cancer is stratified into four distinct clinical subtypes, using three key biomarkers (Her2/Neu gene status, Estrogen and Progesterone receptor status). However, each subtype is a heterogeneous group, displaying significant variation in survival rates and treatment response. New biomarkers are required to provide more precise stratification of breast cancer cohorts to inform personalised treatment options/predict outcomes. Tip60 is a member of the MYST sub-family of histone acetyltransferases (HATs), and is directly involved in genome maintenance, gene regulation and DNA damage response/repair pathways (key chemotherapeutic influencing mechanisms). We aimed to determine if quantifying Tip60 staining patterns improved breast cancer stratification. We defined Tip60 protein in vivo, quantifying location (cytoplasmic, nuclear), percent of cells and staining intensity in a breast cancer tissue microarray (n = 337). A significant association of specific Tip60 staining patterns with breast cancer subtype, ER or PR status and Tumour grade was found. Importantly, low Tip60 mRNA expression correlated with poor overall survival and relapse free survival. We found Tip60 is a biomarker able to stratify breast cancer patients, and low Tip60 expression is a significant risk factor indicating a higher chance of disease reoccurrence. This work highlights Tip60 regulation as a key factor influencing the development of breast cancer.

Correction to: Breast cancer subtype discordance: impact on post-recurrence survival and potential treatment options.

It has been highlighted that the original manuscript [1] contains a typesetting error regarding the authorship.

Breast cancer subtype discordance: impact on post-recurrence survival and potential treatment options.

BACKGROUND: Recent studies have shown that breast cancer subtype can change from the primary tumour to the recurrence. Discordance between primary and recurrent breast cancer has implications for further treatment and ultimately prognosis. The aim of the study was to determine the rate of change between primary and recurrence of breast cancer and to assess the impact of these changes on survival and potential treatment options. METHODS: Patient demographics were collected on those who underwent surgery for breast cancer between 2001 and 2014 and had a recurrence with biopsy results and pathology scoring of both the primary and recurrence. RESULTS: One hundred thirty two consecutive patients were included. There were 31 (23.5%) changes in subtype. Discordance occurred most frequently in luminal A breast cancer (n = 20), followed by triple negative (n = 4), luminal B (n = 3) and HER2 (n = 3). Patients who changed from luminal A to triple negative (n = 18) had a significantly worse post-recurrence survival (p < 0.05) with overall survival approaching significance (p = 0.064) compared to concordant luminal A cases (n = 46). Overall receptor discordance rates were: estrogen receptor 20.4% (n = 27), progesterone receptor 37.7% (n = 50) and HER2 3% (n = 4). Loss of estrogen receptor and progesterone receptor was more common than gain (21 vs. 6 (p = 0.04) and 44 vs. 6 (p = 0.01) respectively). Nine patients (6.8%) gained receptor status potentially impacting treatment options. CONCLUSION: Discordance in subtype and receptor status occurs between primary and recurrent breast cancer, ultimately affecting survival and potentially impacting treatment options.