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

Uptake of breast cancer preventive therapy in the UK: results from a multicentre prospective survey and qualitative interviews

Purpose: Uptake of preventive therapy for women at increased breast cancer risk in England is unknown following the introduction of UK clinical guidelines in 2013. Preventive therapy could create socioeconomic inequalities in cancer incidence if it is more readily accepted by particular socio-demographic groups. In this multicentre study, we investigated uptake of tamoxifen and evaluated socio-demographic and clinical factors associated with initiation. We explored women’s experiences of treatment decision-making using qualitative interview data. Methods: Between September 2015 and December 2016, women (n=732) attending an appointment at one of 20 centres in England to discuss breast cancer risk were approached to complete a survey containing socio-demographic details and nulliparity. Of the baseline survey respondents (n=408/732, 55.7% response rate), self-reported uptake of tamoxifen at 3-month follow-up was reported in 258 (63.2%). Sixteen women participated in semi-structured interviews. Results: One in seven (38/258=14.7%) women initiated tamoxifen. Women who had children were more likely to report use of tamoxifen than those without children (OR=5.26; 95%CI: 1.13–24.49, p=0.035). Interview data suggested that women weigh up risks and benefits of tamoxifen within the context of familial commitments, with exposure to significant other’s beliefs and experiences of cancer and medication a basis for their decision. Conclusions: Uptake of tamoxifen is low in clinical practice. There were no socio-demographic differences in uptake, suggesting that the introduction of breast cancer preventive therapy is unlikely to create socioeconomic inequalities in cancer incidence. Women’s decision-making was influenced by familial priorities, particularly having children

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

Consensus for genes to be included on cancer panel tests offered by UK genetics services: guidelines of the UK Cancer Genetics Group.

Genetic testing for hereditary cancer predisposition has evolved rapidly in recent years with the discovery of new genes, but there is much debate over the clinical utility of testing genes for which there are currently limited data regarding the degree of associated cancer risk. To address the discrepancies that have arisen in the provision of these tests across the UK, the UK Cancer Genetics Group facilitated a 1-day workshop with representation from the majority of National Health Service (NHS) clinical genetics services. Using a preworkshop survey followed by focused discussion of genes without prior majority agreement for inclusion, we achieved consensus for panels of cancer genes with sufficient evidence for clinical utility, to be adopted by all NHS genetics services. To support consistency in the delivery of these tests and advice given to families across the country, we also developed management proposals for individuals who are found to have pathogenic mutations in these genes. However, we fully acknowledge that the decision regarding what test is most appropriate for an individual family rests with the clinician, and will depend on factors including specific phenotypic features and the family structure

Medication beliefs predict uptake of preventive therapy in women at increased risk of breast cancer: a Latent Profile Analysis (Abstract only)

Background: Preventive therapies such as tamoxifen are a risk reduction option for women at increased risk of breast cancer. Uptake of preventive therapies is low. The Self-Regulatory Framework identifies the role of beliefs about medication and its impact on treatment decisionmaking. We examined whether women at increased risk of breast cancer can be categorised into groups with similar medication beliefs and whether belief group membership was prospectively associated with uptake of preventive therapy. Methods: Women (n =732) attending an appointment at one of 20 centres in England to discuss breast cancer risk were approached; 55.7% (408/732) completed a survey containing the Beliefs about Medicines Questionnaire (BMQ) and the Perceived Sensitivity to Medicines (PSM) questionnaire. Self-reported uptake of tamoxifen at 3-month follow-up was reported in 258 (63.2%). The optimal number of medication belief groups were identified using Latent Profile Analysis (LPA). Results: Uptake of tamoxifen was 14.7% (38/258). The LPA model fit statistics supported a 2-group model. Both groups held weak beliefs about their need for tamoxifen for current and future health. Group 2 (38% of the sample) reported stronger concerns about tamoxifen and medicines in general, and stronger perceived sensitivity to the negative effects of medicines compared with Group 1 (62%). In a multivariable model, women classified into Group 2 (low need, higher concerns) were more likely to be: aged ≥50 years (vs. 36–49 years), OR=0.56, 95% CI: 0.34–0.93, p=.024). Women with low necessity and lower concerns (Group 1) were more likely to initiate tamoxifen (18.3%; 33) than those with low necessity and higher concerns (Group 2) (6.4%; 5). After adjusting for demographic and clinical factors, the OR was 3.37 (95% CI: 1.08 – 10.51, p = .036). Conclusions and implications: In this UK multi-centre study, uptake of breast cancer preventive therapy was low. An important subgroup of women reported low need for preventive therapy and strong medication concerns. These women were less likely to initiate tamoxifen. Understanding subgroup differences in medication beliefs may enable the development of personalised interventional approaches for supporting informed treatment decision-making

Risks of breast or ovarian cancer in BRCA1 or BRCA2 predictive test negatives: findings from the EMBRACE study.

Purpose BRCA1/BRCA2 predictive test negatives are proven noncarriers of a BRCA1/BRCA2 mutation that is carried by their relatives. The risk of developing breast cancer (BC) or epithelial ovarian cancer (EOC) in these women is uncertain. The study aimed to estimate risks of invasive BC and EOC in a large cohort of BRCA1/BRCA2 predictive test negatives. Methods We used cohort analysis to estimate incidences, cumulative risks, and standardized incidence ratios (SIRs). Results A total of 1,895 unaffected women were eligible for inclusion in the BC risk analysis and 1,736 in the EOC risk analysis. There were 23 incident invasive BCs and 2 EOCs. The cumulative risk of invasive BC was 9.4% (95% confidence interval (CI) 5.9-15%) by age 85 years and the corresponding risk of EOC was 0.6% (95% CI 0.2-2.6%). The SIR for invasive BC was 0.93 (95% CI 0.62-1.40) in the overall cohort, 0.85 (95% CI 0.48-1.50) in noncarriers from BRCA1 families, and 1.03 (95% CI 0.57-1.87) in noncarriers from BRCA2 families. The SIR for EOC was 0.79 (95% CI 0.20-3.17) in the overall cohort. Conclusion Our results did not provide evidence for elevated risks of invasive BC or EOC in BRCA1/BRCA2 predictive test negatives. Genetics in Medicine advance online publication, 22 March 2018; doi:10.1038/gim.2018.44

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. © 2012 Springer-Verlag

Population Testing for Cancer Predisposing BRCA1/BRCA2 Mutations in the Ashkenazi-Jewish Community: A Randomized Controlled Trial

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

Attitudes in Patients with Autosomal Dominant Polycystic Kidney Disease Toward Prenatal Diagnosis and Preimplantation Genetic Diagnosis

Final publication is available from Mary Ann Liebert, Inc., publishers http://dx.doi.org/10.1089/gtmb.2016.0050AIMS: No recommendations currently exist regarding implementation of both prenatal diagnosis and preimplantation genetic diagnosis (PGD) for autosomal dominant polycystic kidney disease (ADPKD). This study evaluated attitudes in ADPKD patients with either chronic kidney disease (CKD) stages I-IV or end-stage renal failure (ESRF) toward prenatal diagnosis and PGD. METHODS: Ninety-six ADPKD patients were recruited from an outpatient clinic, wards, and dialysis units. Thirty-eight patients had ESRF and 58 had CKD stages I-IV. Participants were given an information sheet on prenatal diagnosis and PGD and subsequently completed a questionnaire. RESULTS: The median age of participants was 51.5 years. Seventeen percent of ADPKD patients with CKD and 18% of ADPKD patients with ESRF would consider prenatal diagnosis and termination of pregnancy for ADPKD. Fifty percent with CKD would have opted for PGD (or might consider it in the future) were it available and funded by the UK National Health Service, compared to 63% in the ESRF group (p = 0.33). Sixty-nine percent in the CKD group and 68% in the ESRF group believed that PGD should be offered to other patients. DISCUSSION: There was a spectrum of attitudes among this cohort. A proportion of patients believe that PGD should be made available to prospective parents with this disease. The discrepancy between the low proportion (17% CKD, 18% ESRF) who would consider prenatal diagnosis and termination of pregnancy and the higher number who hypothetically express an intention or wish to access PGD (50% CKD and 63% ESRF) indicates far greater acceptability for diagnostic methods that occur before embryo implantation. It is not known how the development of methods to identify patients whose renal function is likely to decline rapidly and treatments altering the natural history of ADPKD will affect these attitudes.Peer reviewe

Beliefs About Medication and Uptake of Preventive Therapy in Women at Increased Risk of Breast Cancer: Results From a Multicenter Prospective Study

Introduction Uptake of preventive therapies for breast cancer is low. We examined whether women at increased risk of breast cancer can be categorized into groups with similar medication beliefs, and whether belief group membership was prospectively associated with uptake of preventive therapy. Patients and Methods Women (n = 732) attending an appointment to discuss breast cancer risk were approached; 408 (55.7%) completed the Beliefs About Medicines and the Perceived Sensitivity to Medicines questionnaires. Uptake of tamoxifen at 3 months was reported in 258 (63.2%). The optimal number of belief groups were identified using latent profile analysis. Results Uptake of tamoxifen was 14.7% (38/258). One in 5 women (19.4%; 78/402) reported a strong need for tamoxifen. The model fit statistics supported a 2-group model. Both groups held weak beliefs about their need for tamoxifen for current and future health. Group 2 (38%; 154/406 of the sample) reported stronger concerns about tamoxifen and medicines in general, and stronger perceived sensitivity to the negative effects of medicines compared with group 1 (62%; 252/406). Women with low necessity and lower concerns (group 1) were more likely to initiate tamoxifen (18.3%; 33/180) than those with low necessity and higher concerns (group 2) (6.4%; 5/78). After adjusting for demographic and clinical factors, the odds ratio was 3.37 (95% confidence interval, 1.08-10.51; P = .036). Conclusion Uptake of breast cancer preventive therapy was low. A subgroup of women reported low need for preventive therapy and strong medication concerns. These women were less likely to initiate tamoxifen. Medication beliefs are targets for supporting informed decision-making