Women's responses and understanding of polygenic breast cancer risk information.

It is estimated that polygenic factors can explain up to 18% of familial breast cancer. Clinical implementation of polygenic testing has begun, with several commercial laboratories now testing. Despite commercial implementation, there is little research investigating how women respond and understand polygenic risk information. This study aimed to explore women's experience receiving their personalised polygenic risk score (PRS) and compare responses of women at different levels of polygenic risk. Eligible participants were affected and unaffected women from families clinically assessed to be at high risk for breast cancer who had received their personalised PRS as part of the Variants in Practice Psychosocial Study (ViPPs). In-depth semi-structured interviews were conducted with 21 women (mean age 53.4 years) up to four weeks after receiving their PRS. Interviews were transcribed verbatim and analysed using thematic analysis. Eleven women received a PRS that was in the top quartile of PRS distribution and 10 in the lowest quartile. Women's lived experience with breast cancer informed how they responded to their PRS, constructed and made sense of breast cancer risk following receipt of their PRS, and integrated this new information into their breast cancer risk management. Regardless of polygenic risk level, all participants demonstrated broad knowledge of concepts related to polygenic information and were able to accurately describe the implications of their PRS. Receiving PRS did not appear to negatively impact women's reported distress levels. Our findings suggest polygenic breast cancer information is well received and understood by women at high-risk for breast cancer.

The development and evaluation of a nationwide training program for oncology health professionals in the provision of genetic testing for ovarian cancer patients.

BACKGROUND: BRCA1/2 mutation status has increasing relevance for ovarian cancer treatments, making traditional coordination of genetic testing by genetic services unsustainable. Consequently alternative models of genetic testing have been developed to improve testing at the initial diagnosis for all eligible women. METHODS: A training module to enable mainstreamed genetic testing by oncology healthcare professionals was developed by genetic health professionals. Oncology healthcare professionals completed questionnaires before and 12 months post-training to assess perceived skills, competence and barriers to their coordinating genetic testing for women with high-grade non-mucinous epithelial ovarian cancer. Genetic health professionals were surveyed 12 months post-training to assess perceived barriers to implementation of mainstreaming. RESULTS: 185 oncology healthcare professionals were trained in 42 workshops at 35 Australasian hospitals. Of the 273 tests ordered by oncology healthcare professionals post-training, 241 (93.1%) met national testing guidelines. The number of tests ordered by genetic health professionals reduced significantly (z = 45.0, p = 0.008). Oncology healthcare professionals' perceived barriers to mainstreamed testing decreased from baseline to follow-up (t = 2.39, p = 0.023), particularly perceived skills, knowledge and attitudes. However, only 58% reported either 'always' or 'nearly always' having ordered BRCA testing for eligible patients at 12 months, suggesting oncology healthcare professionals' perceived barriers were not systematically addressed through training. CONCLUSIONS: Oncology healthcare professionals have demonstrated a willingness to be involved in the provision of genetic testing in a mainstreaming model. If oncology services are to hold responsibility for coordinating genetic testing, their readiness will require understanding of barriers not addressed by training alone to inform future intervention design.

Children and young people's understanding of inherited conditions and their attitudes towards genetic testing: A systematic review.

Children and young people are increasingly likely to receive information regarding inherited health risks relevant to their genetic relatives and themselves. We reviewed the literature to determine what children and young people (21 years and younger) understand about inherited conditions and their attitudes towards genetic testing. We screened 1815 abstracts to identify 20 studies representing the perspectives of 1811 children and young people between the ages of 6 and 21 years (1498 children or young people at general population-level risk from 9 studies, 313 affected/at risk from 15 studies). Children and young people at general population-level risk demonstrated a basic understanding that disease predisposition can be inherited within families. Those affected by or at risk of genetic conditions inferred their genetic status from observable, relational characteristics within their family and the results of personal genetic testing if it had occurred, but some misunderstandings of important genetic concepts were evident. Children and young people expressed interest in and a willingness to undertake personal genetic testing, but also articulated concerns about the limitations and risks of testing. Paediatric patients require developmentally-sensitive genetic counselling and support in navigating the unique landscape of their condition.

How are genetic test results being used by Australian life insurers?

In Australia, the USA and many Asian countries the life insurance industry is self-regulated. Individuals must disclose genetic test results known to them in applications for new or updated policies including cover for critical care, income protection and death. There is limited information regarding how underwriting decisions are made for policies with such disclosures. The Australian Financial Services Council (FSC) provided de-identified data collected on applications with genetic test result disclosure from its life insurance member companies 2010-2013 to enable repetition of an independent examination undertaken of applications 1999-2003: age; gender; genetic condition; testing result; decision-maker; and insurance cover. Data was classified as to test result alone or additional other factors relevant to risk and decision. Where necessary, the FSC facilitated clarification by insurers. 345/548 applications related to adult-onset conditions. The genetic test result solely influenced the decision in 165/345 applications: positive (n = 23), negative (n = 139) and pending (n = 3). Detailed analyses of the decisions in each of these result categories are presented with specific details of 11 test cases. Policies with standard decisions were provided for all negative test results with evidence of reassessment of previous non-standard decisions and 20/23 positive results with recognition of risk reduction strategies. Disclosure of positive results for breast/ovarian cancer, Lynch syndrome and hereditary spastic paraplegia, and three pending results, generated non-standard decisions. The examination demonstrates some progress in addressing concerns in regard to utilisation of genetic test information but the self-regulatory system in Australia only goes some way in meeting internationally recommended best practice.

When knowledge of a heritable gene mutation comes out of the blue: treatment-focused genetic testing in women newly diagnosed with breast cancer.

Selection of women for treatment-focused genetic testing (TFGT) following a new diagnosis of breast cancer is changing. Increasingly a patient's age and tumour characteristics rather than only their family history are driving access to TFGT, but little is known about the impact of receiving carrier-positive results in individuals with no family history of cancer. This study assesses the role of knowledge of a family history of cancer on psychosocial adjustment to TFGT in both women with and without mutation carrier-positive results. In-depth semistructured interviews were conducted with 20 women who had undergone TFGT, and who had been purposively sampled to represent women both family history and carrier status, and subjected to a rigorous qualitative analysis. It was found that mutation carriers without a family history reported difficulties in making surgical decisions quickly, while in carriers with a family history, a decision regarding surgery, electing for bilateral mastectomy (BM), had often already been made before receipt of their result. Long-term adjustment to a mutation-positive result was hindered by a sense of isolation not only by those without a family history but also those with a family history who lacked an affected relative with whom they could identify. Women with a family history who had no mutation identified and who had not elected BM reported a lack of closure following TFGT. These findings indicate support deficits hindering adjustment to positive TFGT results for women with and without a family history, particularly in regard to immediate decision-making about risk-reducing surgery.

Melanoma survivors at high risk of developing new primary disease: a qualitative examination of the factors that contribute to patient satisfaction with clinical care.

BACKGROUND: Providing ongoing clinical care that adequately addresses patients' medical, psychosocial and information needs is challenging, particularly for patient groups at increased risk of developing life-threatening disease such as malignant melanoma. This study examined a model of clinical care developed by the High Risk Clinic (HRC) of the Sydney Melanoma Diagnostic Centre in relation to patient satisfaction. METHODS: Semi-structured telephone interviews were conducted and analyzed using the framework of Miles and Huberman, and themes were organized using the qualitative software package, QSR NVivo8. RESULTS: Twenty HRC patients participated in the study (nine men, 11 women; mean age 57.6 years, age range 34-74 years; response rate 91%). Satisfaction with clinical care at the HRC was high. Factors contributing to patient satisfaction included: rapid and regular access to physicians who were perceived by participants as experts, the development of confidence and trust in one's treating doctor, and a sense of being cared about and understood by one's healthcare team. Although one-third of the participants reported some inconveniences in attending the clinic, these were viewed as minor difficulties and not significant barriers to care. Formal psychological support was not sought or expected by participants, although many expressed long-standing melanoma-related fears and concerns. CONCLUSIONS: Accessible, expert medical attention, delivered in a patient-centered manner was integral to melanoma survivors' satisfaction with clinical management. Appropriate referrals to psychological support may further increase satisfaction with clinical care.

There is no decision to make: experiences and attitudes toward treatment-focused genetic testing among women diagnosed with ovarian cancer.

OBJECTIVE: There is growing evidence that the BRCA mutation status of women newly diagnosed with ovarian cancer may be used to make treatment recommendations in the future. This qualitative study aimed to assess women's attitudes and experiences toward treatment-focused genetic testing (TFGT). METHODS: Women (N=22) with ovarian cancer who had either (i) advanced disease and had previously had TFGT (n=12) or (ii) had a recent ovarian cancer diagnosis and were asked about their hypothetical views of TFGT (n=10), were interviewed in-depth. RESULTS: This study demonstrates that patients diagnosed with ovarian cancer found the concept of TFGT acceptable with the primary motivation for genetic testing being to increase their treatment options. Women reported that there was no decision to make about TFGT, and the advantages of TFGT were perceived to outweigh the disadvantages. Many women described elements of resilience and active coping, in the context of hypothetical and actual TFGT. CONCLUSIONS: Resilience and active coping strategies are important factors that warrant investigation as potential moderators of psychological distress in future prospective studies exploring the optimal way of offering BRCA genetic testing to women newly diagnosed with ovarian cancer, and to assess the impact of TFGT upon patients' survival, psychological distress, and quality of life.

A prospective study assessing anxiety, depression and maternal-fetal attachment in women using PGD.

BACKGROUND: PGD has been described in previous cross-sectional and retrospective studies as a stressful experience. No prospective studies of the psychological impact of PGD are currently available. METHODS: Using a prospective study design, validated measures exploring anxiety and depression were used to assess women using PGD prior to treatment, following embryo transfer, following the pregnancy test result and at 24 weeks of pregnancy. Maternal-fetal attachment was also assessed during pregnancy. RESULTS: The prospective design revealed the cyclical pathway through PGD for many women, often comprising repeated cycles of ovarian stimulations and IVF and frozen embryo transfers. As predicted, there were significant fluctuations in women's anxiety scores, with increases observed following embryo transfer and pregnancy testing. Women's anxiety scores returned to baseline levels during pregnancy as assessed at 24 weeks gestation. Depression scores did not significantly fluctuate during PGD. Maternal-fetal attachment scores in this sample did not differ from the normative Australian data. CONCLUSIONS: For some women, the PGD pathway is convoluted and requires multiple IVF cycles and embryo transfers to achieve pregnancy. A subset of women experience significant emotional burden during PGD treatment, and it is these women who require closer attention and support. In this sample, emotional adjustment in pregnancy following PGD appears to be sound.

Women's experience of pre-implantation genetic diagnosis: a qualitative study.

OBJECTIVE: To provide an in-depth account of the experience of pre-implantation genetic diagnosis (PGD). METHOD: Exploratory qualitative interview study. Participants were recruited from one major in vitro fertilization (IVF) clinic in Sydney, Australia. Data were collected through 14 in-depth interviews with women at different stages of PGD, utilized a thematic approach and facilitated by NVivo software. RESULTS: Women reported using PGD as empowering and led them to feel in control of their reproductive futures. Health professionals who did not tell women about PGD were seen as a barrier to accessing treatment. The ability to select embryos free from the genetic condition (for which it was at risk) alleviated stress. Despite this, stress experienced with PGD was significant for women, and often related to past experiences of reproductive trauma and grief. The outcome of embryos was also the cause of stress for women. CONCLUSION: Women undergoing PGD have a diverse range of reproductive and genetic histories, psychosocial circumstances and world views that all interact and impact their experience of PGD. Successful support and care of these women should address all of these factors and tailor the support provided for women using this physically and emotionally complex form of reproductive technology.

Psychological adjustment, knowledge and unmet information needs in women undergoing PGD.

BACKGROUND: Women often enter preimplantation genetic diagnosis (PGD) treatment following traumatic reproductive and genetic histories, the detrimental psychological effects of which are known to be long lasting in some cases. In addition, attempting IVF with PGD requires an in-depth understanding of the aspects of the technology. The level of information that is required and retained by women entering treatment is important for clinicians to understand. To date, neither of these issues has been explored empirically. To address this, we assessed mood and information-seeking behavior in a sample of women entering PGD. METHODS: Fifty women entering PGD treatment completed self-administered questionnaires that assessed anxiety, depression, knowledge of technical aspects of PGD, expectancy of establishing a pregnancy and unmet information needs. RESULTS: Anxiety and depression rates were similar to normal population data. State anxiety was associated with degree of financial worry [beta = 0.36, t = 2.60, P = 0.01, 95% confidence interval (CI): 0.03-0.23], and living in an inner metropolitan area (beta = 0.30, P = 0.03, 95% CI: 0.32-10.81). Unmet information needs were positively associated with women's education (beta = 0.97, P = 0.01, 95% CI: 0.22-1.73). Lastly, expectancy of establishing a pregnancy was above that of what clinicians provide as realistic PGD pregnancy chances and, unexpectedly, was also associated with degree of financial worry (beta = 0.36, P = 0.01, 95% CI: 0.07-0.56). CONCLUSIONS: Women entering PGD are emotionally well adjusted although the financial costs associated with PGD are associated with increases in anxiety. The study is limited by its small sample size and the fact that partners were not assessed.

Psychological impact of preimplantation genetic diagnosis: a review of the literature.

Preimplantation genetic diagnosis (PGD) was first reported as successful in humans in the early 1990s and nearly two decades later the psychological impact of PGD has not yet been clearly defined. As PGD requires the use of IVF, this paper provides a brief summary of literature related to the various psychological aspects of IVF followed by a review of the literature related to the psychological and broader psychosocial impact of PGD. The current literature includes attitudinal studies of couples for whom PGD may be beneficial and results suggest that those with traumatic reproductive and genetic histories are more likely to find PGD an acceptable treatment option. A small number of studies have used samples of women and couples who have used PGD. Due to a general lack of homogeneity in scope, method and results, these studies have not provided a uniform understanding of the PGD experience. Promisingly, however, two studies on parents of children born after PGD that explored parental stress show no differences between PGD, IVF and natural conception couples. The paper concludes that the missing link in the literature is a prospective study of PGD using validated psychological scales. Suggestions for future research are provided.

'Start the conversation': the New South Wales (Australia) family health history campaign.

BACKGROUND: Evidence that family health history (FHH) informs recommendations for appropriate early detection strategies used for the prevention of many health conditions underscores the importance of optimizing a patient's knowledge of his/her personal FHH. For some conditions, FHH also underpins identifying those at potentially high risk for whom genetic testing may be possible and suitable to further inform the advice. The Family Health History Campaign 'Start the Conversation' was conducted in New South Wales (Australia) in August 2006 as a small state-wide media campaign with the aim of encouraging individuals to discuss and gather their FHH information about several conditions and report it to their doctor. Campaign development included consultations with consumers and primary care practitioners (general practitioners - GPs), development of campaign resources, and establishment of partnerships. METHODS: Evaluation methodologies included community poll surveys pre- and post-campaign, a GP mail survey, and website usage analysis. RESULTS: While only 112/403 of the polled community reported hearing about the campaign in the media, 48% of those men and women were encouraged to start the conversation with their families. Limited findings from the GP survey respondents suggested they were engaged, made aware of the potential lack of patient knowledge about FHH and generated referral for several high-risk patients. CONCLUSION: Campaigns that use the media to encourage the community to take action and also engage the GPs can create a supportive environment that has the potential to increase the accuracy with reporting of FHH to maximize benefit for early detection and prevention.

Treatment-focused DNA testing for newly diagnosed breast cancer patients: some implications for clinical practice.

There is accumulating evidence that women with breast cancer due to a familial BRCA1 or BRCA2 mutation benefit from specific surgical and chemotherapeutic treatment strategies. However, the rapid identification of such patients during the acute phase of treatment raises a number of issues. This study investigated Australian opinion leaders' views on the issues arising from such 'treatment-focused' genetic testing. Semi-structured interviews with 34 opinion leaders working in cancer genetics were undertaken. Interviewees acknowledged the introduction of treatment-focused DNA testing has the potential to positively transform the management of breast cancer patients, but were concerned that certain ethical and logistical issues have yet to be addressed. These include decision-making and consent, the familial nature of genetic information, and the management of genetics services within familial cancer clinics in the public hospital system in Australia. Service providers will need to have policies and strategies for managing the increased demand. It will also be necessary to include genetic counseling services within familial cancer clinics in the care pathway for newly diagnosed patients prior to any DNA testing to determine adjuvant treatment; such services may be more cost-effective than expecting surgeons and medical oncologists to fulfill this role.

Investigating genetic discrimination in Australia: a large-scale survey of clinical genetics clients.

We report first results from the Australian Genetic Discrimination Project of clinical genetics services clients' perceptions and experiences regarding alleged differential treatment associated with having genetic information. Adults (n = 2667) who had presented from 1998 to 2003 regarding predictive or presymptomatic testing for designated mature-onset conditions were surveyed; 951/1185 respondents met inclusion criteria for current asymptomatic status. Neurological conditions and familial cancers were primary relevant conditions for 87% of asymptomatic respondents. Specific incidents of alleged negative treatment, reported by 10% (n = 93) of respondents, occurred in life insurance (42%), employment (5%), family (22%), social (11%) and health (20%) domains. Respondents where neuro-degenerative conditions were relevant were more likely overall to report incidents and significantly more likely to report incidents in the social domain. Most incidents in the post-test period occurred in the first year after testing. Only 15% of respondents knew where to complain officially if treated negatively because of genetics issues. Recommendations include the need for increased community and clinical education regarding genetic discrimination, for extended clinical genetics sector engagement and for co-ordinated monitoring, research and policy development at national levels in order for the full benefits of genetic testing technology to be realised.

A comparison of community, clinician, and patient preferences for naming a cancer-related mutation.

This study compared language preferences to describe a cancer-related mutation in three groups: 253 members of the general community, 20 clinicians working in cancer genetics, and 269 individuals at increased risk of carrying a cancer-related mutation (including 198 women with a strong family history of breast and/or ovarian cancer, and 71 individuals with a family history of hereditary non-polyposis colorectal cancer). In the community sample, 'faulty gene' was the preferred term to describe a cancer-related mutation, although females, those affected by cancer and those who felt cancer had a large impact on their lives were more likely to prefer the terms 'gene change' or 'altered gene'. In contrast, the clinicians' preference ratings for 'faulty gene' and 'gene change' were equal. When forced to choose between 'faulty gene' and 'altered gene', the high-risk patient group reported preferring 'faulty gene', although over 40% were happy with either term. Further research investigating individuals' understanding of the different terms that can be used to describe a cancer-related mutation, and the functional impact of these terms on patients' thoughts and feelings about their condition and on their health-related behavior after genetic counseling would be worthwhile.

Genetics education in a culturally diverse population--lessons learnt, future directions.

To provide equitable genetics education services, the needs of a culturally and linguistically diverse (CALD) population must be addressed. The mission of the Centre for Genetics Education (CGE) in Australia articulates a commitment to fostering community partnerships, implementing educational strategies and evaluating the impact of genetics information and technology on society. The aim of this report is to review the ways in which CALD groups have been partners in the planning and implementation of genetics educational strategies of the Centre. Responding to the community and respecting its contribution has helped forge these partnerships and implement appropriate and relevant educational strategies. The partnerships have been effective in modulating both the protocols used in producing resources, the resource content itself, and the provision of more appropriately targeted resources for these community groups.

Evaluation of a Tay-Sachs disease screening program.

Tay-Sachs Disease (TSD) is an autosomal recessive neurodegenerative disorder. TSD is prevalent in the Ashkenazi Jewish population, and carrier screening programs have been implemented worldwide in these communities. A screening program initiated in 1997 involving the Melbourne Jewish community (Australia) incorporated education, counselling and carrier testing of high-school students aged 15 to 18 years. This study aimed to assess the participation rates, level of knowledge obtained and predicted feelings and attitudes of the students involved. Seven hundred and ten students participated, there was a 67% uptake for testing with a carrier rate of 1 in 28 determined. The level of knowledge of the students following education was high and of relative importance in regard to decision making, as were their feelings and attitudes about genetic testing for carrier status. A significant impediment to test uptake was the need for blood sampling, resulting in a recommendation for the introduction of DNA analysis on cheek brush samples. The evaluation of this program has given a wider scope for further development as well as providing valuable information for the implementation of community screening programs.

Cultural aspects of cancer genetics: setting a research agenda.

BACKGROUND: Anecdotal evidence suggests that people from non-Anglo-Celtic backgrounds are under-represented at familial cancer clinics in the UK, the USA, and Australia. This article discusses cultural beliefs as a potential key barrier to access, reviews previous empirical research on cultural aspects of cancer genetics, draws implications from findings, and sets a research agenda on the inter-relationships between culture, cancer genetics, and kinship. METHODS: The CD-ROM databases MEDLINE, PsychLIT, CINAHL, and Sociological Abstracts were searched from 1980 onwards. RESULTS: Cultural aspects of cancer genetics is the focus of an emerging body of publications. Almost all studies assessed African-American women with a family history of breast cancer and few studies included more diverse samples, such as Americans of Ashkenazi Jewish background or Hawaiian- and Japanese-Americans. Our analysis of published reports suggests several directions for future research. First, an increased focus on various Asian societies appears warranted. Research outside North America could explore the extent to which findings can be replicated in other multicultural settings. In addition, control group designs are likely to benefit from systematically assessing culture based beliefs and cultural identity in the "majority culture" group used for comparative purposes. CONCLUSION: More data on which to base the provision of culturally appropriate familial cancer clinic services to ethnically diverse societies are needed. Empirical data will assist with culturally appropriate categorisation of people from other cultures into risk groups based on their family histories and provide the basis for the development of culturally appropriate patient education strategies and materials.