Claire Foster

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.

Balancing autonomy and responsibility: the ethics of generating and disclosing genetic information

Using data obtained during a retrospective interview study of 30 women who had undergone genetic testing—BRCA1/2 mutation searching—this paper describes how women, previously diagnosed with breast/ovarian cancer, perceive their role in generating genetic information about themselves and their families. It observes that when describing their motivations for undergoing DNA testing and their experiences of disclosing genetic information within the family these women provide care based ethical justifications for their actions. Finally, it argues that generating genetic information and disclosing this information to kin raise different types of ethical issues. The implications of these findings for ethical debates about informed choice in the context of genetic testing are discussed.

Psychosocial implications of living 5 years or more following a cancer diagnosis: a systematic review of the research evidence

Mortality associated with cancer remains high, but more people are surviving cancer. Some people experience long-term problems associated with cancer and its treatment, and there is a need to know how to support them. This systematic literature review explores primary research for psychosocial implications of long-term survival (>or=5 years) following a cancer diagnosis and interventions designed to address psychosocial problems in the long term. A systematic search of BIDS, BNI, Cancer.gov, CINAHL, Medline, PsychINFO and Web of Science was conducted to identify research publications from 1960 to 2006. Papers were selected on the basis of pre-defined criteria and rated by three independent coders. Forty-three studies met the eligibility criteria. These indicated that most people experience few problems five or more years after their diagnosis of cancer. However, 20-30% of survivors consistently reported problems associated with cancer and its treatment including physical problems, poorer quality of life, psychological distress, sexual problems, problems with social relationships and financial concerns. Not all cancer types are represented in this review. Only two intervention studies met the eligibility criteria. Research is needed to establish appropriate interventions to support those experiencing problems in the long term to enhance well-being.

Psychosocial impact of breast/ovarian (BRCA1/2) cancer-predictive genetic testing in a UK multi-centre clinical cohort

This multi-centre UK study assesses the impact of predictive testing for breast and ovarian cancer predisposition genes (BRCA1/2) in the clinical context. In the year following predictive testing, 261 adults (59 male) from nine UK genetics centres participated; 91 gene mutation carriers and 170 noncarriers. Self-report questionnaires were completed at baseline (pre-genetic testing) and 1, 4 and 12 months following the genetic test result. Men were assessed for general mental health (by general health questionnaire (GHQ)) and women for general mental health, cancer-related worry, intrusive and avoidant thoughts, perception of risk and risk management behaviour. Main comparisons were between female carriers and noncarriers on all measures and men and women for general mental health. Female noncarriers benefited psychologically, with significant reductions in cancer-related worry following testing (P<0.001). However, younger female carriers (<50 years) showed a rise in cancer-related worry 1 month post-testing (P<0.05). This returned to pre-testing baseline levels 12 months later, but worry remained significantly higher than noncarriers throughout (P<0.01). There were no significant differences in GHQ scores between males and females (both carriers and noncarriers) at any time point. Female carriers engaged in significantly more risk management strategies than noncarriers in the year following testing (e.g. mammograms; 92% carriers vs 30% noncarriers). In the 12 months post-testing, 28% carriers had bilateral risk-reducing mastectomy and 31% oophorectomy. Oophorectomy was confined to older (mean 41 yrs) women who already had children. However, worry about cancer was not assuaged by surgery following genetic testing, and this requires further investigation. In all, 20% of female carriers reported insurance problems. The data show persistent worry in younger female gene carriers and confirm changes in risk management consistent with carrier status. Men were not adversely affected by genetic testing in terms of their general mental health.

The health and well-being of cancer survivors in the UK: findings from a population-based survey

Background:To compare self-reported health and well-being in a sample of cancer survivors with individuals who have not had cancer and with individuals who have a serious chronic condition other than cancer.Patients and methodsA cross-sectional survey drawn from an online panel of 400 000 UK citizens supplemented with other online recruitment and telephone recruitment. The participants were 4892 individuals 30 years of age or above, including 780 individuals with a previous cancer diagnosis, 1372 individuals with one or more of 10 chronic conditions but not cancer and 2740 individuals without a previous cancer diagnosis or chronic condition. Thirteen measures of health and well-being were constructed from answers to 25 survey items covering physical, psychological and social dimensions of health and well-being.Results:Cancer survivors were significantly more likely to report poor health outcomes across all 13 measures than those with no history of cancer or a chronic condition. The adjusted odds ratios for cancer survivors with no chronic conditions compared with healthy participants ranged from 1.37 (95% confidence interval (CI): 1.31–1.96) for emotional well-being to 3.34 (95% CI: 2.74–4.08) for number of health professionals consulted in the last 12 months. The health profile of cancer survivors was similar to those with a history of a serious chronic health condition.Conclusions:A substantial number of individuals who have had a diagnosis of cancer experience ongoing poor health and well-being following cancer and cancer treatment. The results of this study provide an initial basis for the development of specific help and support for cancer survivors.

Recovery and self-management support following primary cancer treatment

Background:Around 2 million people are living with or beyond cancer in the UK. However, experiences and needs following primary treatment are relatively neglected. Following treatment, survivors may feel particularly vulnerable and face threats to their identity. We present a conceptual framework to inform areas of self-management support to facilitate recovery of health and well-being following primary cancer treatment.Methods:To explain the framework, we draw on data from two studies: UK-wide consultation about cancer patients’ research priorities and survivors’ self-management in the year following primary cancer treatment.Results:Self-confidence may be low following treatment. Recovery includes rebuilding lost confidence. Support to manage the impact of cancer on everyday life was a priority. Self-management support included health professionals, peers, employers, family, friends and online resources. However, support was not always available and confidence to access support could be low.Conclusion:Cancer survivors may struggle to self-manage following primary treatment where confidence is low or support is lacking. Low confidence may be a significant barrier to accessing support. Supporting recovery of self-confidence is an important aspect of recovery alongside physical and psychosocial problems in the context of changing health care and cancer follow-up.

Communication about genetic testing in families of male BRCA1/2 carriers and non-carriers: patterns, priorities and problems

This qualitative interview study explored the way in which information about predictive BRCA1/2 testing and its implications for children is disseminated within the families of at‐risk men who undergo genetic testing. Twenty‐nine in‐depth interviews were carried out with family members [male patients (n = 17), their partners (n = 8) and adult children (n = 4)]. These explored the following themes: experiences of cancer and genetic testing, decision‐making about testing and the communication of test results and genetic information within the immediate family. The interviews revealed that both male patients and their partners perceive themselves, rather than health professionals, as responsible for disclosing information about genetic testing and genetic risks to their children. Parents described three different communication strategies for the disclosure of genetic information to their children: complete openness, limited disclosure and total secrecy. The adoption of a particular communication strategy was justified in terms of childrens rights to information vs their parental duties to protect their children from anxiety‐provoking information. Some of the problems arising from the adoption of different disclosure patterns are identified and the implications for clinical practice are discussed.

The research priorities of patients attending UK cancer treatment centres: findings from a modified nominal group study.

Members of the public are increasingly consulted over health care and research priorities. Patient involvement in determining cancer research priorities, however, has remained underdeveloped. This paper presents the findings of the first consultation to be conducted with UK cancer patients concerning research priorities. The study adopted a participatory approach using a collaborative model that sought joint ownership of the study with people affected by cancer. An exploratory, qualitative approach was used. Consultation groups were the main method, combining focus group and nominal group techniques. Seventeen groups were held with a total of 105 patients broadly representative of the UK cancer population. Fifteen areas for research were identified. Top priority areas included the impact cancer has on life, how to live with cancer and related support issues; risk factors and causes of cancer; early detection and prevention. Although biological and treatment related aspects of science were identified as important, patients rated the management of practical, social and emotional issues as a higher priority. There is a mismatch between the research priorities identified by participants and the current UK research portfolio. Current research activity should be broadened to reflect the priorities of people affected by the disease.

What Facilitates or Impedes Family Communication Following Genetic Testing for Cancer Risk? A Systematic Review and Meta-Synthesis of Primary Qualitative Research

To systematically review and meta-synthesise primary qualitative research findings regarding family communication following genetic testing of cancer risk, in order to inform development of effective interventions. Systematic searches of CINAHL, Embase, Medline, British Nursing Index and PsycINFO databases were undertaken and relevant studies identified using strict criteria. The selected primary qualitative studies were appraised for quality and relevance by three independent researchers and then synthesized using a “Framework” approach. Fourteen (4.3%) studies met the inclusion criteria. The following factors influenced family communication following genetic testing for late-onset hereditary cancer: the informant’s feelings about informing relatives about genetic testing; the perceived relevance of the information to other family members and their anticipated reactions; the “closeness” of relationships within the family; family rules and patterns (e.g., who is best placed to share information with whom); finding the right time and level of disclosure; and the supportive role of heath care professionals. The themes identified in this review could provide practitioners with a useful framework for discussing family communication with those undergoing genetic testing. This framework focuses on helping health care professionals to facilitate family communication. The next step will be the development of an intervention to directly support people in talking to their relatives.

The physical and practical problems experienced by cancer survivors: A rapid review and synthesis of the literature

PURPOSE A rapid and comprehensive review to identify what is known and not known about the physical and practical problems faced by adult cancer survivors. METHODS A systematic literature review process was used. This focused on published reviews to enable a fast but rigorous identification of both the gaps and well-researched areas within survivorship. RESULTS The search identified 5121 reviews, of which 42 were screened and 9 met the quality and inclusion criteria. The majority of papers focused on physical well being (n = 6) with the remaining papers focusing on practical well being (employment and finance). The quality of the reviews varied (ranging from weak to good). Gaps identified include sexual function, lower-limb lymphoedema, peripheral neuropathy, bladder and GI problems, hormonal sequelae, older cancer survivors, work impact of cancer and context-specific unmet supportive care needs. The review found a lack of standardised nomenclature for survivorship and methodological limitations. CONCLUSIONS Four main gaps in knowledge relating to the practical and physical problems associated with cancer survivorship have been identified. These are key symptoms, unmet supportive care needs, employment and older cancer survivors, and should be addressed by future research and systematic literature reviews. Work is also needed to address the nomenclature of survivorship and to improve the methodology of research into cancer survivors (including standardised measures, theoretical frameworks, longitudinal design, inclusion of older survivors and age-matched controls for comparison). The review highlighted the need for better research within the identified areas in order to improve the experiences of cancer survivors.