Randomised trial of population-based BRCA testing in Ashkenazi Jews: long-term secondary lifestyle behavioural outcomes.

OBJECTIVE: Ashkenazi-Jewish (AJ) population-based BRCA testing is acceptable, cost-effective and amplifies primary prevention for breast & ovarian cancer. However, data describing lifestyle impact are lacking. We report long-term results of population-based BRCA testing on lifestyle behaviour and cancer risk perception. DESIGN: Two-arm randomised controlled trials (ISRCTN73338115, GCaPPS): (a) population-screening (PS); (b) family history (FH)/clinical criteria testing. SETTING: North London AJ-population. POPULATION/SAMPLE: AJ women/men >18 years. EXCLUSIONS: prior BRCA testing or first-degree relatives of BRCA-carriers. METHODS: Participants were recruited through self-referral. All participants received informed pre-test genetic counselling. The intervention included genetic testing for three AJ BRCA-mutations: 185delAG(c.68_69delAG), 5382insC(c.5266dupC) and 6174delT(c.5946delT). This was undertaken for all participants in the PS arm and participants fulfilling FH/clinical criteria in the FH arm. Patients filled out customised/validated questionnaires at baseline/1-year/2-year/3-year follow-ups. Generalised linear-mixed models adjusted for covariates and appropriate contrast tests were used for between-group/within-group analysis of lifestyle and behavioural outcomes along with evaluating factors associated with these outcomes. Outcomes are adjusted for multiple testing (Bonferroni method), with P < 0.0039 considered significant. OUTCOME MEASURES: Lifestyle/behavioural outcomes at baseline/1-year/2-year/3-year follow-ups. RESULTS: 1034 participants were randomised to PS (n = 530) or FH (n = 504) arms. No significant difference was identified between PS- and FH-based BRCA testing approaches in terms of dietary fruit/vegetable/meat consumption, vitamin intake, alcohol quantity/ frequency, smoking behaviour (frequency/cessation), physical activity/exercise or routine breast mammogram screening behaviour, with outcomes not affected by BRCA test result. Cancer risk perception decreased with time following BRCA testing, with no difference between FH/PS approaches, and the perception of risk was lowest in BRCA-negative participants. Men consumed fewer fruits/vegetables/vitamins and more meat/alcohol than women (P < 0.001). CONCLUSION: Population-based and FH-based AJ BRCA testing have similar long-term lifestyle impacts on smoking, alcohol, dietary fruit/vegetable/meat/vitamin, exercise, breast screening participation and reduced cancer risk perception.

Stepped approach to improving sexual function after gynaecological cancer: the SAFFRON feasibility RCT.

BACKGROUND: Women affected by gynaecological cancer are often unaware of the sexual consequences of both the cancer and its treatment. Most do not receive appropriate advice or help to recover sexual function, and the effect on their sexuality may be profound, both physically and emotionally. However, several potential therapies can be effective in helping recover some sexual engagement and change self-perception around sex. A major initial challenge is informing and involving patients in an appropriate and sensitive manner, and a further issue is delivering therapies in busy gynaelogical oncology clinics. This study was conceived in response to a National Institute for Health Research (NIHR) Health Technology Assessment (HTA) call asking for proposals to improve sexual functioning in women treated for gynaecological cancer while taking into account associated issues of mood. Existing evidence-based therapies for improving sexual function after cancer treatment were adapted and placed within a 'stepped care' model for delivering these in the NHS setting. An assessment and treatment stepping algorithm was developed in parallel, both to assign women to a treatment level at assessment and to follow their progress session by session to advise on changing intervention level. The assessment tool was applied to all participants on the principle that the problem was sexual difficulty, not the cancer of origin. PARTICIPANTS: Women aged > 18 years (with partners at their choice) treated for any gynaecological malignancy with surgery and/or chemotherapy and/or radiation at University College London Hospital or Bristol Gynaecological cancer centres, minimally 3 months post end of treatment, of any sexual orientation, with sexual function difficulties identified by three initial screening questions. DESIGN: A feasibility two-arm, parallel-group randomised controlled pilot trial. SETTING: Two NHS gynaecological cancer centres, one in London and one in Bristol. INTERVENTIONS: A three-level stepped care intervention. OBJECTIVE: To assess the feasibility of conducting a full-scale investigation of stepped therapy and indicate the potential benefits to patients and to the NHS generally. PRIMARY OUTCOME MEASURES: Recruitment to study, proportion of women stepping up, number of usable data points of all measures and time points over length of trial, and retention of participants to end of trial. RESULTS: Development of the intervention and accompanying algorithm was completed. The study was stopped before the recruitment stage and, hence, no randomisation, recruitment, numbers analysed, outcomes or harms were recorded. LIMITATIONS: As the study did not proceed, the intervention and its accompanying algorithm have not been evaluated in practice, and the capacity of the NHS system to deliver it has not been examined. CONCLUSIONS: None, as the study was halted. FUTURE WORK: The intervention could be studied within a clinical setting; however, the experience of the study group points to the need for psychosocial studies in medical settings to establish pragmatic and innovative mechanisms to ensure adequate resource when extending staff clinical skills and time to deliver any new intervention for the duration of the trial. TRIAL REGISTRATION: Current Controlled Trials ISRCTN12010952 and ClinicalTrials.gov NCT02458001. FUNDING: This project was funded by the NIHR HTA programme and will be published in full in Health Technology Assessment; Vol. 23, No. 5. See the NIHR Journals Library website for further project information.

Women affected by gynaecological cancer are often unaware of the sexual consequences of the cancer and its treatment. Most do not receive appropriate help to recover sexual function, and the physical and mental impact on their sexuality may be profound. However, several therapies could be effective in helping recovery. A major initial challenge is informing and involving patients appropriately and sensitively, and a further challenge is delivering therapies in busy cancer clinics. This study was conceived in response to the funder's call asking for proposals to improve sexual functioning in women treated for gynaecological cancer while taking into account associated issues of mood. Existing evidence-based therapies for improving sexual function after gynaecological cancer treatment were adapted and a new therapy for complex difficulties was devised. Three levels of intervention were developed and placed into a 'stepped care' model: a self-help intervention, a clinical nurse specialist-delivered intervention and a clinical psychologist high-level intervention for problems not responding to levels 1 and 2. In parallel, an assessment and treatment algorithm was developed to assess women and follow their progress closely to inform whether or not their intervention level should be changed. However, major difficulties were encountered: procedural and logistical delays in setting up the study, both at the beginning across a range of hospitals and, later, at the point of training staff within the NHS to deliver the interventions within their clinical workload. Issues such as maternity leave with untrained locum cover led to nursing staff being unable to free up qualified staff to be part of the study. It is hoped that the existing developments can be tested in a future study to determine (1) if they are effective and (2) whether or not they can be delivered within the NHS.

Attitudes towards a programme of risk assessment and stratified management for ovarian cancer: a focus group study of UK South Asians' perspectives.

OBJECTIVE: Population-based risk assessment, using genetic testing and the provision of appropriate risk management, could lead to prevention, early detection and improved clinical management of ovarian cancer (OC). Previous research with mostly white British participants found positive attitudes towards such a programme. The current study aimed to explore the attitudes of South Asian (SA) women and men in the UK with the aim of identifying how best to implement such a programme to minimise distress and maximise uptake. DESIGN: Semistructured qualitative focus group discussions. SETTING: Community centres across North London and Luton. PARTICIPANTS: 49 women and 13 men who identified as SA (Indian, Pakistani or Bangladeshi), which constitutes the largest non-European ethnic minority group in the UK. METHODS: Seven community-based focus groups were held. Group discussions were transcribed verbatim, coded and analysed thematically. RESULTS: Awareness and knowledge of OC symptoms and specific risk factors was low. The programme was acceptable to most participants and attitudes to it were generally positive. Participants' main concerns related to receiving a high-risk result following the genetic test. Younger women may be more cautious of genetic testing, screening or risk-reducing surgery due to the importance of marriage and childbearing in their SA cultures. CONCLUSIONS: A crucial first step to enable implementation of population-based genetic risk assessment and management in OC is to raise awareness of OC within SA communities. It will be important to engage with the SA community early on in programme implementation to address their specific concerns and to ensure culturally tailored decision support.

Health care professionals' attitudes towards population-based genetic testing and risk-stratification for ovarian cancer: a cross-sectional survey.

BACKGROUND: Ovarian cancer is usually diagnosed at a late stage when outcomes are poor. Personalised ovarian cancer risk prediction, based on genetic and epidemiological information and risk stratified management in adult women could improve outcomes. Examining health care professionals' (HCP) attitudes to ovarian cancer risk stratified management, willingness to support women, self-efficacy (belief in one's own ability to successfully complete a task), and knowledge about ovarian cancer will help identify training needs in anticipation of personalised ovarian cancer risk prediction being introduced. METHODS: An anonymous survey was distributed online to HCPs via relevant professional organisations in the UK. Kruskal-Wallis tests and pairwise comparisons were used to compare knowledge and self-efficacy scores between different types of HCPs, and attitudes toward population-based genetic testing and risk stratified management were described. Content analysis was undertaken of free text responses concerning HCPs willingness to discuss risk management options with women. RESULTS: One hundred forty-six eligible HCPs completed the survey: oncologists (31%); genetics clinicians (30%); general practitioners (22%); gynaecologists (10%); nurses (4%); and 'others'. Scores for knowledge of ovarian cancer and genetics, and self-efficacy in conducting a cancer risk consultation were generally high but significantly lower for general practitioners compared to genetics clinicians, oncologists, and gynaecologists. Support for population-based genetic testing was not high (<50%). Attitudes towards ovarian cancer risk stratification were mixed, although the majority of participants indicated a willingness to discuss management options with patients. CONCLUSIONS: Larger samples are required to investigate attitudes to population-based genetic testing for ovarian cancer risk and to establish why some HCPs are hesitant to offer testing to all adult female patients. If ovarian cancer risk assessment using genetic testing and non-genetic information including epidemiological information is rolled out on a population basis, training will be needed for HCPs in primary care to enable them to provide appropriate support to women at each stage of the process.

Anticipated health behaviour changes and perceived control in response to disclosure of genetic risk of breast and ovarian cancer: a quantitative survey study among women in the UK.

BACKGROUND: Genetic risk assessment for breast cancer and ovarian cancer (BCOC) is expected to make major inroads into mainstream clinical practice. It is important to evaluate the potential impact on women ahead of its implementation in order to maximise health benefits, as predictive genetic testing without adequate support could lead to adverse psychological and behavioural responses to risk disclosure. OBJECTIVE: To examine anticipated health behaviour changes and perceived control to disclosure of genetic risk for BCOC and establish demographic and person-specific correlates of adverse anticipated responses in a population-based sample of women. DESIGN: Cross-sectional quantitative survey study carried out by the UK Office for National Statistics in January and March 2014. SETTING: Face-to-face computer-assisted interviews conducted by trained researchers in participants' homes. PARTICIPANTS: 837 women randomly chosen from households across the UK identified from the Royal Mail's Postcode Address File. OUTCOME MEASURES: Anticipated health behaviour change and perceived control to disclosure of BCOC risk. RESULTS: In response to a genetic test result, most women (72%) indicated 'I would try harder to have a healthy lifestyle', and over half (55%) felt 'it would give me more control over my life'. These associations were independent of demographic factors or perceived risk of BCOC in Bonferroni-corrected multivariate analyses. However, a minority of women (14%) felt 'it isn't worth making lifestyle changes' and that 'I would feel less free to make choices in my life' (16%) in response to BCOC risk disclosure. The former belief was more likely to be held by women who were educated below university degree level (P<0.001) after adjusting for other demographic and person-specific correlates. CONCLUSION: These findings indicate that women in the UK largely anticipate that they would engage in positive health behaviour changes in response to BCOC risk disclosure.

Impact of a decision aid about stratified ovarian cancer risk-management on women's knowledge and intentions: a randomised online experimental survey study.

BACKGROUND: Risk stratification using genetic and other types of personal information could improve current best available approaches to ovarian cancer risk reduction, improving identification of women at increased risk of ovarian cancer and reducing unnecessary interventions for women at lower risk. Amounts of information given to women may influence key informed decision-related outcomes, e.g. knowledge. The primary aim of this study was to compare informed decision-related outcomes between women given one of two versions (gist vs. extended) of a decision aid about stratified ovarian cancer risk-management. METHODS: This was an experimental survey study comparing the effects of brief (gist) information with lengthier, more detailed (extended) information on cognitions relevant to informed decision-making about participating in risk-stratified ovarian cancer screening. Women with no personal history of ovarian cancer were recruited through an online survey company and randomised to view the gist (n = 512) or extended (n = 519) version of a website-based decision aid and completed an online survey. Primary outcomes were knowledge and intentions. Secondary outcomes included attitudes (values) and decisional conflict. RESULTS: There were no significant differences between the gist and extended conditions in knowledge about ovarian cancer (time*group interaction: F = 0.20, p = 0.66) or intention to participate in ovarian cancer screening based on genetic risk assessment (t(1029) = 0.43, p = 0.67). There were also no between-groups differences in secondary outcomes. In the sample overall (n = 1031), knowledge about ovarian cancer increased from before to after exposure to the decision aid (from 5.71 to 6.77 out of a possible 10: t = 19.04, p < 0.001), and 74% of participants said that they would participate in ovarian cancer screening based on genetic risk assessment. CONCLUSIONS: No differences in knowledge or intentions were found between women who viewed the gist version and women who viewed the extended version of a decision aid about risk-stratified ovarian cancer screening. Knowledge increased for women in both decision aid groups. Further research is needed to determine the ideal volume and type of content for decision aids about stratified ovarian cancer risk-management. TRIAL REGISTRATIONS: This study was registered with the ISRCTN registry; registration number: ISRCTN48627877 .

Awareness, knowledge, perceptions, and attitudes towards genetic testing for cancer risk among ethnic minority groups: a systematic review.

BACKGROUND: Genetic testing for risk of hereditary cancer can help patients to make important decisions about prevention or early detection. US and UK studies show that people from ethnic minority groups are less likely to receive genetic testing. It is important to understand various groups' awareness of genetic testing and its acceptability to avoid further disparities in health care. This review aims to identify and detail awareness, knowledge, perceptions, and attitudes towards genetic counselling/testing for cancer risk prediction in ethnic minority groups. METHODS: A search was carried out in PsycInfo, CINAHL, Embase and MEDLINE. Search terms referred to ethnicity, genetic testing/counselling, cancer, awareness, knowledge, attitudes, and perceptions. Quantitative and qualitative studies, written in English, and published between 2000 and 2015, were included. RESULTS: Forty-one studies were selected for review: 39 from the US, and two from Australia. Results revealed low awareness and knowledge of genetic counselling/testing for cancer susceptibility amongst ethnic minority groups including African Americans, Asian Americans, and Hispanics. Attitudes towards genetic testing were generally positive; perceived benefits included positive implications for personal health and being able to inform family. However, negative attitudes were also evident, particularly the anticipated emotional impact of test results, and concerns about confidentiality, stigma, and discrimination. Chinese Australian groups were less studied, but of interest was a finding from qualitative research indicating that different views of who close family members are could impact on reported family history of cancer, which could in turn impact a risk assessment. CONCLUSION: Interventions are needed to increase awareness and knowledge of genetic testing for cancer risk and to reduce the perceived stigma and taboo surrounding the topic of cancer in ethnic minority groups. More detailed research is needed in countries other than the US and across a broader spectrum of ethnic minority groups to develop effective culturally sensitive approaches for cancer prevention.

Inviting end-of-life talk in initial CALM therapy sessions: A conversation analytic study.

OBJECTIVE: To examine how end-of-life talk is initiated in CALM therapy sessions with advanced cancer patients. METHODS: Conversation analysis was used to systematically examine the sequences where talk about death was raised in the first sessions of ten patients. RESULTS: Open questions about the patients' experiences, feelings or understanding in the context of talk about their troubles, were found to regularly elicit talk concerning end-of-life. These questions were designed in ways that invite patients to discuss troubling aspects of their cancer journey, without making discussion of this topic an interactional requirement. That is, the interactional work required to not engage in such talk is minimised. This choice is provided through the open question design, the degree to which negative feeling descriptors are specified, and the sequential context of the question. CONCLUSION: The analysis shows that therapists provide patients with the opportunity to talk about end-of-life in a way that is supportive of the therapeutic relationship. The readiness of patients to engage in end-of-life talk displays the salience of this topic, as well as the reflective space provided by CALM therapy. PRACTICE IMPLICATIONS: The results provide important insight into the process of CALM therapy, which can be used to guide training.

Ovarian Cancer Follow-up: A Preliminary Comparison of 2 Approaches.

OBJECTIVE: The aim of the study was to perform a preliminary comparison of quality of life (QoL) and patient satisfaction in individualized nurse-led follow-up versus conventional medical follow-up in ovarian cancer. METHODS: One hundred twelve women who received a diagnosis of ovarian, fallopian tube, or peritoneal cancer, completed primary treatment by surgery alone or with chemotherapy, irrespective of outcome with regard to remission, and expected survival of more than 3 months. Fifty-seven participants were randomized to individualized follow-up and 55 patients to conventional follow-up. Well-being was measured at baseline and at 3, 6, 12, and 24 months after randomization for QoL (QLQ-C30 [European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire], QLQ-Ov28), the Hospital Anxiety and Depression Scale (HADS), and a Patient Satisfaction Questionnaire (PSQ-III). The primary endpoints were the effects of follow-up on each of the scores (via hierarchical mixed-effects model) and on relapse-free time (via Cox model). The total cost of follow-up was compared between each group. RESULTS: There was evidence for a QoL and patient satisfaction benefit for individualized versus standard follow-up (QLQ-C30, P = 0.013; 95% confidence interval, -0.03 to -0.001; PSQ-III P = 0.002; 95% confidence interval, -0.003 to -0.015; QLQ-Ov28, P = 0.14). Hospital Anxiety and Depression Scale data provided no evidence in favor of either treatment (P = 0.42). Delivered to protocol individualized follow-up resulted in a delay in the presentation of symptomatic relapse (P = 0.04), although the effect on survival in this study is unknown. Cost was £700 lower on average for the individualized follow-up group, but the difference was not statistically significant at the 5% level (P = 0.07). CONCLUSIONS: Individualized follow-up was superior to conventional follow-up in 3 of the 4 QoL and patient satisfaction surveys in this preliminary study. Further prospective studies are needed in a larger population.Trial registration number is ISRCTN59149551.

Genetic testing and personalized ovarian cancer screening: a survey of public attitudes.

BACKGROUND: Advances in genetic technologies are expected to make population-wide genetic testing feasible. This could provide a basis for risk stratified cancer screening; but acceptability in the target populations has not been explored. METHODS: We assessed attitudes to risk-stratified ovarian cancer (OC) screening based on prior genetic risk assessment using a survey design. Home-based interviews were carried out by the UK Office of National Statistics in a population-based sample of 1095 women aged 18-74. Demographic and personal correlates of attitudes to risk-stratified OC screening based on prior genetic risk assessment were determined using univariate analyses and adjusted logistic regression models. RESULTS: Full data on the key analytic questions were available for 829 respondents (mean age 46 years; 27 % 'university educated'; 93 % 'White'). Relatively few respondents felt they were at 'higher' or 'much higher' risk of OC than other women of their age group (7.4 %, n = 61). Most women (85 %) said they would 'probably' or 'definitely' take up OC genetic testing; which increased to 88 % if the test also informed about breast cancer risk. Almost all women (92 %) thought they would 'probably' or 'definitely' participate in risk-stratified OC screening. In multivariate logistic regression models, university level education was associated with lower anticipated uptake of genetic testing (p = 0.009), but with more positive attitudes toward risk-stratified screening (p <0.001). Perceived risk was not significantly associated with any of the outcome variables. CONCLUSIONS: These findings give confidence in taking forward research on integration of novel genomic technologies into mainstream healthcare.

Cluster-randomised non-inferiority trial comparing DVD-assisted and traditional genetic counselling in systematic population testing for BRCA1/2 mutations.

BACKGROUND: Newer approaches to genetic counselling are required for population-based testing. We compare traditional face-to-face genetic counselling with a DVD-assisted approach for population-based BRCA1/2 testing. METHODS: A cluster-randomised non-inferiority trial in the London Ashkenazi Jewish population. INCLUSION CRITERIA: Ashkenazi Jewish men/women >18 years; exclusion criteria: (a) known BRCA1/2 mutation, (b) previous BRCA1/2 testing and (c) first-degree relative of BRCA1/2 carrier. Ashkenazi Jewish men/women underwent pre-test genetic counselling prior to BRCA1/2 testing in the Genetic Cancer Prediction through Population Screening trial (ISRCTN73338115). Genetic counselling clinics (clusters) were randomised to traditional counselling (TC) and DVD-based counselling (DVD-C) approaches. DVD-C involved a DVD presentation followed by shorter face-to-face genetic counselling. Outcome measures included genetic testing uptake, cancer risk perception, increase in knowledge, counselling time and satisfaction (Genetic Counselling Satisfaction Scale). Random-effects models adjusted for covariates compared outcomes between TC and DVD-C groups. One-sided 97.5% CI was used to determine non-inferiority. SECONDARY OUTCOMES: relevance, satisfaction, adequacy, emotional impact and improved understanding with the DVD; cost-minimisation analysis for TC and DVD-C approaches. RESULTS: 936 individuals (clusters=256, mean-size=3.6) were randomised to TC (n=527, clusters=134) and DVD-C (n=409, clusters=122) approaches. Groups were similar at baseline, mean age=53.9 (SD=15) years, women=66.8%, men=33.2%. DVD-C was non-inferior to TC for increase in knowledge (d=-0.07; lower 97.5% CI=-0.41), counselling satisfaction (d=-0.38, 97.5% CI=1.2) and risk perception (d=0.08; upper 97.5% CI=3.1). Group differences and CIs did not cross non-inferiority margins. DVD-C was equivalent to TC for uptake of genetic testing (d=-3%; lower/upper 97.5% CI -7.9%/1.7%) and superior for counselling time (20.4 (CI 18.7 to 22.2) min reduction (p<0.005)). 98% people found the DVD length and information satisfactory. 85-89% felt it improved their understanding of risks/benefits/implications/purpose of genetic testing. 95% would recommend it to others. The cost of genetic counselling for DVD-C=£7787 and TC=£17 307. DVD-C resulted in cost savings=£9520 (£14/volunteer). CONCLUSIONS: DVD-C is an effective, acceptable, non-inferior, time-saving and cost-efficient alternative to TC. TRIAL REGISTRATION NUMBER: ISRCTN 73338115.

Adjusting the frequency of mammography screening on the basis of genetic risk: Attitudes among women in the UK.

PURPOSE: To explore public attitudes towards modifying frequency of mammography screening based on genetic risk. METHODS: Home-based interviews were carried out with a population-based sample of 942 women aged 18-74 years in the UK. Demographic characteristics and perceived breast cancer (BC) risk were examined as predictors of support for risk-stratified BC screening and of the acceptability of raised or lowered screening frequency based on genetic risk, using multivariate logistic regression. RESULTS: Over two-thirds of respondents (65.8%) supported the idea of varying screening frequency on the basis of genetic risk. The majority (85.4%) were willing to have more frequent breast screening if they were found to be at higher risk, but fewer (58.8%) were willing to have less frequent screening if at lower risk (t (956) = 15.6, p < 0.001). Ethnic minority status was associated with less acceptability of more frequent screening (OR = 0.40, 95% CI = 0.21-0.74), but there were no other significant demographic correlates. Higher perceived risk of BC was associated with greater acceptability of more frequent screening (OR = 1.71, 95%CI = 1.27-2.30). CONCLUSION: Women were positive about adjusting the frequency of mammography screening in line with personal genetic risk, but it will be important to develop effective communication materials to minimise resistance to reducing screening frequency for those at lower genetic risk.

Population-based genetic risk prediction and stratification for ovarian cancer: views from women at high risk.

There is an opportunity to improve outcomes for ovarian cancer (OC) through advances in risk stratification, early detection and diagnosis. A population-based OC genetic risk prediction and stratification program is being developed. A previous focus group study with individuals from the general population showed support for the proposed program. This qualitative interview study explores the attitudes of women at high risk of OC. Eight women participated in one-on-one, in-depth, semi-structured interviews to explore: experiences of learning of OC risk, risk perceptions, OC knowledge and awareness, and opinions on risk stratification approach. There was evidence of strong support for the proposed program. Benefits were seen as providing reassurance to women at low risk, and reducing worry in women at high risk through appropriate clinical management. Stratification into 'low' and 'high' risk groups was well-received. Participants were more hesitant about stratification to the 'intermediate' risk group. The data suggest formats to effectively communicate OC risk estimates will require careful thought. Interactions with GPs were highlighted as a barrier to OC risk assessment and diagnosis. These results are encouraging for the possible introduction and uptake of a risk prediction and stratification program for OC in the general population.

Population testing for cancer predisposing BRCA1/BRCA2 mutations in the Ashkenazi-Jewish community: a randomized controlled trial.

BACKGROUND: Technological advances raise the possibility of systematic population-based genetic testing for cancer-predisposing mutations, but it is uncertain whether benefits outweigh disadvantages. We directly compared the psychological/quality-of-life consequences of such an approach to family history (FH)-based testing. METHODS: In a randomized controlled trial of BRCA1/2 gene-mutation testing in the Ashkenazi Jewish (AJ) population, we compared testing all participants in the population screening (PS) arm with testing those fulfilling standard FH-based clinical criteria (FH arm). Following a targeted community campaign, AJ participants older than 18 years were recruited by self-referral after pretest genetic counseling. The effects of BRCA1/2 genetic testing on acceptability, psychological impact, and quality-of-life measures were assessed by random effects regression analysis. All statistical tests were two-sided. RESULTS: One thousand, one hundred sixty-eight AJ individuals were counseled, 1042 consented, 1034 were randomly assigned (691 women, 343 men), and 1017 were eligible for analysis. Mean age was 54.3 (SD = 14.66) years. Thirteen BRCA1/2 carriers were identified in the PS arm, nine in the FH arm. Five more carriers were detected among FH-negative FH-arm participants following study completion. There were no statistically significant differences between the FH and PS arms at seven days or three months on measures of anxiety, depression, health anxiety, distress, uncertainty, and quality-of-life. Contrast tests indicated that overall anxiety (P = .0001) and uncertainty (P = .005) associated with genetic testing decreased; positive experience scores increased (P = .0001); quality-of-life and health anxiety did not change with time. Overall, 56% of carriers did not fulfill clinical criteria for genetic testing, and the BRCA1/2 prevalence was 2.45%. CONCLUSION: Compared with FH-based testing, population-based genetic testing in Ashkenazi Jews doesn't adversely affect short-term psychological/quality-of-life outcomes and may detect 56% additional BRCA carriers.

Cost-effectiveness of population screening for BRCA mutations in Ashkenazi jewish women compared with family history-based testing.

BACKGROUND: Population-based testing for BRCA1/2 mutations detects the high proportion of carriers not identified by cancer family history (FH)-based testing. We compared the cost-effectiveness of population-based BRCA testing with the standard FH-based approach in Ashkenazi Jewish (AJ) women. METHODS: A decision-analytic model was developed to compare lifetime costs and effects amongst AJ women in the UK of BRCA founder-mutation testing amongst: 1) all women in the population age 30 years or older and 2) just those with a strong FH (≥10% mutation risk). The model assumes that BRCA carriers are offered risk-reducing salpingo-oophorectomy and annual MRI/mammography screening or risk-reducing mastectomy. Model probabilities utilize the Genetic Cancer Prediction through Population Screening trial/published literature to estimate total costs, effects in terms of quality-adjusted life-years (QALYs), cancer incidence, incremental cost-effectiveness ratio (ICER), and population impact. Costs are reported at 2010 prices. Costs/outcomes were discounted at 3.5%. We used deterministic/probabilistic sensitivity analysis (PSA) to evaluate model uncertainty. RESULTS: Compared with FH-based testing, population-screening saved 0.090 more life-years and 0.101 more QALYs resulting in 33 days' gain in life expectancy. Population screening was found to be cost saving with a baseline-discounted ICER of -£2079/QALY. Population-based screening lowered ovarian and breast cancer incidence by 0.34% and 0.62%. Assuming 71% testing uptake, this leads to 276 fewer ovarian and 508 fewer breast cancer cases. Overall, reduction in treatment costs led to a discounted cost savings of £3.7 million. Deterministic sensitivity analysis and 94% of simulations on PSA (threshold £20000) indicated that population screening is cost-effective, compared with current NHS policy. CONCLUSION: Population-based screening for BRCA mutations is highly cost-effective compared with an FH-based approach in AJ women age 30 years and older.

Identifying hopelessness in population research: a validation study of two brief measures of hopelessness.

OBJECTIVE: Hopelessness is an important construct in psychosocial epidemiology, but there is great pressure on the length of questionnaire measures in large-scale population and clinical studies. We examined the validity and test-retest reliability of two brief measures of hopelessness, an existing negatively worded two-item measure of hopelessness (Brief-H-Neg) and a positively worded version of the same instrument (Brief-H-Pos). DESIGN: Cohort study. SETTING: Control arm of the UK Collaborative Trial of Ovarian Cancer Screening. PARTICIPANTS: A non-clinical research-based sample of 5000 postmenopausal women selected from 56 512 participants. PRIMARY AND SECONDARY OUTCOME MEASURES: Spearman's rank correlation of brief measures of hopelessness with the Beck Hopelessness Scale (BHS). Spearman's rank correlation with the Centre for Epidemiological Studies Depression Scale (CES-D) and change in mean score on repeat testing. METHODS: Two short hopelessness measures, a negatively worded brief measure of hopelessness (Brief-H-Neg) and a positively worded brief measure of hopelessness (Brief-H-Pos), were administered by postal questionnaire to 5000 women together with the 20-item BHS and 20-item CES-D. The Brief-H-Neg and Brief-H-Pos were readministered to 500 women after a 2-week interval. RESULTS: 2413 postmenopausal women (mean age 68.9 years) completed the questionnaire. The Brief-H-Neg and Brief-H-Pos correlated 0.93 and 0.87 with the BHS after correction for attenuation and their association with the CES-D mirrored that seen with the BHS (Spearman's rank correlation 0.88 and 0.68, respectively). There was no change in mean scores on the two measures with repeat testing in the 433 women who completed them and test-retest reliability was good (intraclass correlations Brief-H-Neg 0.67 and Brief-H-Pos 0.72). CONCLUSIONS: These findings provide support for the validity of the Brief-H-Neg and Brief-H-Pos. These brief measures are likely to be useful in large population studies assessing hopelessness. TRIAL REGISTRATION NUMBER: NCT00058032.

Telephone peer support for women with gynaecological cancer: benefits and challenges for supporters.

OBJECTIVE: Despite the prevalence of one-to-one peer support programmes for people with cancer, little research has examined its impact on the supporters themselves. This qualitative study examined a telephone-delivered one-to-one peer support intervention for women with gynaecological cancer, focussing on supporters' subjective experiences of benefits or costs to themselves and challenges arising in the support process. METHODS: Semi-structured interviews (N = 24) were conducted with 16 women who provided peer support for 24 patients. Transcripts were analysed thematically using the Framework approach. RESULTS: Participants described significant personal benefits of providing support, including enhanced self-esteem and well-being, and gaining a new perspective and closure on their cancer experience. They experienced no adverse consequences, but several challenges arose, for example, finding a balance between emotional involvement and detachment, and supporting someone with a poor prognosis or high levels of negative emotion. Their accounts indicated resourcefulness in managing the challenges. CONCLUSIONS: Providing peer support has a valuable role to play in cancer survivorship; it can facilitate the final stages of moving away from the role of patient and help to promote a more confident post-cancer sense of self. However, readiness to provide support and the availability of backup from health-care professionals appear essential. The findings have implications for the selection, training and supervision of peer supporters. Future studies should routinely measure outcomes for peer supporters.

Annual outpatient hysteroscopy and endometrial sampling (OHES) in HNPCC/Lynch syndrome (LS).

BACKGROUND: LS women have a 40-60% lifetime risk of endometrial cancer (EC). Most international guidelines recommend screening. However, data on efficacy are limited. PURPOSE: To assess the performance of OHES for EC screening in LS and compare it with transvaginal ultrasound (TVS) alone. METHODS: A prospective observational cohort study of LS women attending a tertiary high-risk familial gynaecological cancer clinic was conducted. LS women opting for EC screening underwent annual OHES and TVS. Histopathological specimens were processed using a strict protocol. Data of women screened between October 2007 and March 2010 were analysed from a bespoke database. Histology was used as the gold standard. Diagnostic accuracy of OHES was compared with TVS using specificity, and positive (PLR) and negative (NLR) likelihood ratios. RESULTS: Forty-one LS women underwent 69 screens (41 prevalent, 28 incident). Four (three prevalent, one incident) women were detected to have EC/atypical endometrial hyperplasia (AEH), five had endometrial polyps and two had endometrial hyperplasia (EH) on OHES. TVS detected two of four EC/AEH. OHES had similar specificity of 89.8% (CI 79.2, 96.2%), but higher PLR 9.8 (CI 4.6, 21) and lower NLR (zero) compared to TVS: specificity 84.75%(CI 73, 92.8%), PLR 3.28 (CI 1.04, 10.35) and NLR 0.59 (CI 0.22, 1.58). No interval cancers occurred over a median follow-up of 22 months. The annual incidence was 3.57% (CI 0.09, 18.35) for EC, 10.71% (CI 2.27, 28.23) for polyps and 21.4% (CI 8.3, 40.1) for any endometrial pathology. CONCLUSIONS: Our findings suggest that in LS, annual OHES is acceptable and has high diagnostic accuracy for EC/AEH screening. Larger international studies are needed for confirmation, given the relatively small numbers of LS women at individual centres. It reinforces the current recommendation that endometrial sampling is crucial when screening these women.

Family history and women with ovarian cancer: is it asked and does it matter?: An observational study.

OBJECTIVE: The objective of the study was to determine how many women in an ovarian cancer (OC) study cohort had a family history (FH) recorded in their case notes and whether appropriate action was taken on the basis of that FH. METHODS: This was a review of patient case-note data of women in a randomized controlled trial of follow-up after primary treatment for OC. Available case notes of 114 women recruited at 3 UK gynecologic cancer centers in a 2-year period between January 2006 and 2008 were examined. Case-note entries for the period from first hospital consultation to 2 years after completion of primary treatment were included. Outcome measures were (1) recording of an FH of cancer in the case notes, (2) whether appropriate action had been taken on the basis of the FH in those women with affected relatives, and (3) characterizing insufficient FH records. RESULTS: Family history was not consistently recorded. Although FH was recorded in the majority of women, 14 women had no FH recorded. In 63 women, the FH was recorded as not significant, and in 15 cases, FH information was insufficient to complete a risk assessment. Twenty-two women had significant FH meeting criteria for specialist genetics referral. In 15 of these 22 cases, the relevant history suggestive of hereditary breast cancer and OC (due to BRCA1 or BRCA2 mutations) or Lynch syndrome had been documented, but no action was recorded, and its significance was not appreciated. CONCLUSIONS: These data indicate that training in recognizing relevant FH is needed for clinicians looking after women with OC. Research is necessary to determine the barriers in taking and interpreting an FH and to determine the optimal time for broaching FH issues during a woman's care pathway. This will improve the accuracy of FH recording and ensure families with OC have access to appropriate surveillance and genetic testing.