Nicholas J. Hulbert-Williams

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

IntroductionBreast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice.MethodsMore than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer ‘stem’ cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account.ResultsThe 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working.ConclusionsWith resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years.

Anxiety, depression and quality of life after cancer diagnosis: what psychosocial variables best predict how patients adjust?

Significant numbers of cancer patients suffer distress, reduced quality of life and various other psychological problems. Evidence regarding psychological predictors of these outcomes is inconsistent. This study explored a range of predictors using an established psychological framework to identify the most important predictors of cancer adjustment, and when these are best assessed for optimal outcome prediction.

Personalised cancer follow-up: risk stratification, needs assessment or both?

There are approximately 2 million people now living with or beyond cancer in the UK (Maddams et al, 2009) and this number is increasing. Cancer survivors can experience physical, psychological and social consequences as a result of the disease and the treatments received (Jefford et al, 2008; Foster et al, 2009). The effects may be immediate, some of which will resolve and others may persist and become long-term. Late effects can also occur and the interval between the end of treatment and onset can range from a few weeks (e.g. lymphoedema after axillary node removal) to several years (e.g. heart disease following radiotherapy to the chest area). Problems will be individual to each patient due to a unique combination of circumstances including the site and stage of the cancer, the type of treatment(s) given, the age of the patient, genetic factors, concomitant co-morbidities, family and social circumstances, and personality traits.

Unmet psychosocial needs in haematological cancer: a systematic review

PurposePsychosocial need implies a desire or requirement for support that underlies a person’s psychological, social and emotional wellbeing. This is not a new concept in the wider cancer literature, yet remains a relatively unexplored area in relation to haematological malignancies. The well-recognised differences between haematological and other types of cancer diagnosis warrant further investigation to try and highlight the potential differences in the needs of this patient group.MethodA systematic review of key online databases and psycho-oncology journals was conducted to identify papers that formally assessed unmet psychosocial needs in adults with a diagnosis of haematological cancer. The breadth of methodologies of included studies made a meta-analytical approach unfeasible, therefore studies were analysed using a narrative synthesis approach.ResultsEighteen studies were found to be relevant and a specific focus was placed on those papers that looked solely at participants with a haematological diagnosis. The key areas of need identified were: psychological need, notably fear of recurrence; information needs; and needs relating to both family and healthcare professionals. Fear of recurrence was the most commonly identified psychosocial need within this literature.ConclusionsThe clinical implications of these findings highlight the need for more widespread access to psychological support for haematology patients and for more to be done to tackle patients’ fears and concerns throughout the course of their illness. Assessment and identification of unmet needs is an important step enabling the development of clinical services that support and maintain psychological wellbeing through treatment and into survivorship.

The role of relationship attachment in psychological adjustment to cancer in patients and caregivers: a systematic review of the literature

The objective of this works is to report the results of a systematic review to evaluate the role of attachment in adjustment to cancer for patients and those close to them.

Patient-reported depression measures in cancer: a meta-review

The patient-reported depression measures that perform best in oncology settings have not yet been identified. We did a meta-review to integrate the findings of reviews of more than 50 depression measures used in adults with, or recovering from, any type of cancer. We searched Medline, PsycINFO, Embase, and grey literature from 1999 to 2014 to identify 19 reviews representing 372 primary studies. 11 reviews were rated as being of high quality (defined as meeting at least 20 criteria in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement). The Hospital Anxiety Depression Scale (HADS) was the most thoroughly evaluated measure, but was limited by cutpoint variability. The HADS had moderate screening utility indices and was least recommended in advanced cancer or palliative care. The Beck Depression Inventory was more generalisable across cancer types and disease stages, with good indices for screening and case finding. The Center for Epidemiologic Studies Depression Scale was the best-weighted measure in terms of responsiveness. This meta-review provides a comprehensive overview of the strengths and limitations of available depression measures. It can inform the choice of the best measure for specific settings and purposes.

Attitudes toward euthanasia and physician-assisted suicide: a study of the multivariate effects of healthcare training, patient characteristics, religion and locus of control

Public and healthcare professionals differ in their attitudes towards euthanasia and physician-assisted suicide (PAS), the legal status of which is currently in the spotlight in the UK. In addition to medical training and experience, religiosity, locus of control and patient characteristics (eg, patient age, pain levels, number of euthanasia requests) are known influencing factors. Previous research tends toward basic designs reporting on attitudes in the context of just one or two potentially influencing factors; we aimed to test the comparative importance of a larger range of variables in a sample of nursing trainees and non-nursing controls. One hundred and fifty-one undergraduate students (early-stage nursing training, late-stage nursing training and non-nursing controls) were approached on a UK university campus and asked to complete a self-report questionnaire. Participants were of mixed gender and were on average 25.5 years old. No significant differences in attitude were found between nursing and non-nursing students. There was a significant positive correlation between higher religiosity and positive attitude toward euthanasia (r=0.19, p<0.05) and a significant negative relationship between internal locus of control and positive attitude toward PAS (r=−0.263, p<0.01). Multivariate analyses revealed differing predictor models for attitudes towards euthanasia and PAS, and confirm the importance of individual differences in determining these attitudes. The unexpected direction of association between religiosity and attitudes may reflect a broader cultural shift in attitudes since earlier research in this area. Furthermore, these findings suggest it possible that experience, more than training itself, may be a bigger influence on attitudinal differences in healthcare professionals.

New paradigms for BRCA1/BRCA2 testing in women with ovarian cancer: results of the Genetic Testing in Epithelial Ovarian Cancer (GTEOC) study

Background Over recent years genetic testing for germline mutations in BRCA1/BRCA2 has become more readily available because of technological advances and reducing costs. Objective To explore the feasibility and acceptability of offering genetic testing to all women recently diagnosed with epithelial ovarian cancer (EOC). Methods Between 1 July 2013 and 30 June 2015 women newly diagnosed with EOC were recruited through six sites in East Anglia, UK into the Genetic Testing in Epithelial Ovarian Cancer (GTEOC) study. Eligibility was irrespective of patient age and family history of cancer. The psychosocial arm of the study used self-report, psychometrically validated questionnaires (Depression Anxiety and Stress Scale (DASS-21); Impact of Event Scale (IES)) and cost analysis was performed. Results 232 women were recruited and 18 mutations were detected (12 in BRCA1, 6 in BRCA2), giving a mutation yield of 8%, which increased to 12% in unselected women aged <70 years (17/146) but was only 1% in unselected women aged ≥70 years (1/86). IES and DASS-21 scores in response to genetic testing were significantly lower than equivalent scores in response to cancer diagnosis (p<0.001). Correlation tests indicated that although older age is a protective factor against any traumatic impacts of genetic testing, no significant correlation exists between age and distress outcomes. Conclusions The mutation yield in unselected women diagnosed with EOC from a heterogeneous population with no founder mutations was 8% in all ages and 12% in women under 70. Unselected genetic testing in women with EOC was acceptable to patients and is potentially less resource-intensive than current standard practice.

The Mini-Mental Adjustment to Cancer Scale: re-analysis of its psychometric properties in a sample of 160 mixed cancer patients

The mini‐Mental Adjustment to Cancer Scale is designed to assess psychological responses to cancer diagnosis and is widely used in research and clinical practice. Recent evidence demonstrates adequate convergent validity but inconsistent internal consistency and factor structure. This study aimed to provide a parsimonious factor structure with clinical utility.

Facilitating Collaborative Learning Using Online Wikis: Evaluation of Their Application Within Postgraduate Psychology Teaching

Virtual learning environments (VLEs) are helpful in achieving a blended learning approach to higher education. Online wikis are proposed as a potentially useful method to encourage collaborative learning through the VLE. The present study integrated wiki software into a module for Masters-level applied psychology students. Seventeen students participated in a week-long online group-based wiki task as a standard part of their course. The use of wiki technology to develop an innovative research idea was evaluated both by analysis of output (tracking of engagement with the intervention) and by self-report questionnaire (evaluation of the intervention) collected from a subsample of 14 students. Results indicate that the students enjoyed the task and perceived educational benefit from it. However, the content of the wikis created suggests that the instructions given to the students may not have been clear enough, and in particular that students were unsure of what the nature and purpose of a wiki is. Students clearly needed more preparatory training in using this technology, and clearer explanation of expected outputs, before beginning this task. This study provides further evidence that students benefit from, and enjoy, blended learning approaches and that wikis represent a useful way to integrate blended and collaborative learning principles.