Breast cancer polygenic risk scores: a 12-month prospective study of patient reported outcomes and risk management behavior.

PURPOSE: To prospectively assess patient reported outcomes and risk management behavior of women choosing to receive (receivers) or decline (decliners) their breast cancer polygenic risk score (PRS). METHODS: Women either unaffected or affected by breast cancer and from families with no identified pathogenic variant in a breast cancer risk gene were invited to receive their PRS. All participants completed a questionnaire at study enrollment. Receivers completed questionnaires at two weeks and 12 months after receiving their PRS, and decliners a second questionnaire at 12 months post study enrollment. RESULTS: Of the 208 participants, 165 (79%) received their PRS. Among receivers, there were no changes in anxiety or distress following testing. However, compared to women with a low PRS, those with a high PRS reported greater genetic testing-specific distress, perceived risk, decisional regret, and less genetic testing-positive response. At 12 months, breast screening and uptake of risk-reducing strategies were consistent with current Australian guidelines of breast cancer risk management. Reasons for declining PRS included being unable to attend the appointment in person and concerns over potential emotional response. CONCLUSION: The outcomes of the study provide insight into women's responses to receiving PRS and highlight the issues that need to be addressed in the associated model of genetic counseling.

Assessment of the Value of Tumor Variation Profiling Perceived by Patients With Cancer.

Importance: Use of tumor molecular profiling (MP) is entering routine clinical practice; however, little is known about how much and why patients value MP. Objective: To examine the perceived value of MP to patients with advanced cancer and factors associated with perceived value. Design, Setting, and Participants: A cross-sectional survey that included willingness-to-pay trade-off scenarios was administered to participants after consent and before MP. A total of 777 participants (94% response rate) were recruited from the Molecular Screening and Therapeutics Program. Eligible patients had advanced solid cancers of any histologic type, were receiving or had completed their last line of effective therapy, had an Eastern Cooperative Oncology Group Performance Status 0 to 3, and had sufficient accessible tissue for MP. The participants were recruited between October 24, 2017, and March 12, 2019, and data analysis was conducted from March 13 to April 14, 2019. Main Outcomes and Measures: Willingness to pay for MP was assessed via hypothetical trade-off scenarios varying in the actionable return rate (1%, 20%, or 40%) and cost (A$0, A$300 [US$210], A$1000 [US $700], A$3000 [US $2100], or A$10 000 [US $7000]). Ordinal regressions were used to explore factors associated with willingness to have and pay for MP. Results: Of 777 participants (405 women [52%]; mean [SD] age, 55.47 [14.26] years), 689 patients (89%) would have MP for as little as a 1% actionable return rate. Fifty-six patients (7%) would require at least a 20% return rate and 11 patients (1%) would require at least a 40% return rate. Fifteen patients (2%) consistently chose not to have the test; 6 participants (0.8%) had missing values on this item. Participants were willing to pay a median of A$1000 if the actionable return rate was 1% and A$3000 for an actionable return rate of 20% to 40%. Of 762 individuals who agreed to testing, 482 patients (64%) were consistently unwilling to pay A$10 000, regardless of the actionable return rate. Patients born in Australia or New Zealand were more likely to want MP (eg, participants born in South Asia had an ordered odds for the tipping point of 7.74 [95% CI, 1.67-36.05; P = .009] times higher than Australian- and/or New Zealand-born participants). Patients born in Australia or New Zealand were also more willing to pay A$1000 or A$3000 (eg, participants born in Western Europe had an ordered odds for the tipping point for paying A$1000 of 1.74 [95% CI, 1.01-3.00; P = .048] times higher than Australian- and/or New Zealand-born participants). People with a medical- or science-related occupation and with more negative attitudes toward uncertainty were more likely to pay A$10 000 (eg, A$10 000 tipping point-ordered odds of participants with a medical- or science-related occupation was 0.49 [95% CI, 0.7-0.87; P = .02] times that of participants without a medical- or science-related occupation). Conclusions and Relevance: This study found apparent high interest in but lower willingness to pay for MP among patients with advanced cancer. Ability to pay may limit access to MP. Ongoing societal debate is required to establish the value of MP and whether subsidization is needed to ensure equity of access.

Evaluation of telephone genetic counselling to facilitate germline BRCA1/2 testing in women with high-grade serous ovarian cancer.

Systemic healthcare issues and geographical challenges restrict women's access to BRCA1/2 testing to inform the use of tailored treatments for high-grade serous ovarian cancer. Consequently, BRCA1/2 testing in this population is low and improved testing pathways are urgently needed. This study aimed to determine the acceptability and feasibility of telephone genetic counselling (TGC) to facilitate treatment-focused BRCA1/2 testing in Australia for women with high-grade serous ovarian cancer. Women who received TGC were invited to complete a survey examining their experiences of the service. A cost analysis was conducted to compare the service to standard, in-person genetic counselling. One hundred and seven women responded (48% response rate); 8 had a BRCA1/2 variant affecting function. Geographical barriers prevented women from accessing genetic services in the past. All participants had a positive attitude towards testing, and regret following testing was minimal. While the impact of testing was greater for those with a positive test result, overall, genetic testing did not put the additional psychosocial burden on the participants. Participant's evaluations of the telephone interactions with the genetic counsellors were highly satisfactory. The service was also found to be cost-effective. This model of telephone genetic counselling was an acceptable and effective way to reduce barriers to BRCA1/2 testing for women with ovarian cancer.

Assessing the medical workforces perceived barriers to the prescription of risk-reducing medication for women at high-risk of breast cancer.

This study aims to determine the attitudes and barriers of Australian oncology health professionals towards using tamoxifen as a breast cancer risk-reducing medication (RRM). Our target group was health professionals involved in breast cancer risk assessment or treatment. Members of relevant medical organizations in Australia and New Zealand were invited to participate in a web-based survey assessing: their attitudes towards tamoxifen as a RRM; which health professionals they felt were responsible for initiating and monitoring women on RRM and their views on workforce issues related to RRM prescription. There were 100 respondents, including 33 genetic health professionals, 32 medical oncologists and 20 surgeons. Respondents perceived tamoxifen to be effective as a RRM (99%). However, only 41% of prescribing health professionals (n = 64) had ever prescribed tamoxifen as a RRM. Overall, survey respondents felt that the initiation of RRM was the role of specialists. Assessing a patient's risk of breast cancer was reported to be the role of cancer geneticists/familial cancer clinicians (74%) and medical oncologists (66%). Discussion about the use of RRM was reported to be the role of these same groups (84% and 85% respectively). Medical oncologists (83%) and breast physicians (70%) were most frequently considered to be responsible for initiating the prescription and monitoring women once commenced on RRM (72% and 71% respectively). Oncology health professionals express confidence in the effectiveness of tamoxifen as a RRM despite reporting low prescription rates. Findings demonstrate that these oncology health professionals felt that initiation of RRM was the role of cancer specialists, despite preventative medicine being seen as a primary care activity. If uptake among at-risk women increases, this will put a significant burden on cancer services and GPs will need to take on a greater role in the delivery of RRM.

Streamlined genetic education is effective in preparing women newly diagnosed with breast cancer for decision making about treatment-focused genetic testing: a randomized controlled noninferiority trial.

PURPOSE: Increasingly, women newly diagnosed with breast cancer are being offered treatment-focused genetic testing (TFGT). As the demand for TFGT increases, streamlined methods of genetic education are needed. METHODS: In this noninferiority trial, women aged <50 years with either a strong family history (FH+) or other features suggestive of a germ-line mutation (FH-) were randomized before definitive breast cancer surgery to receive TFGT education either as brief written materials (intervention group (IG)) or during a genetic counseling session at a familial cancer clinic (usual-care group (UCG)). Women completed self-report questionnaires at four time points over 12 months. RESULTS: A total of 135 women were included in the analysis, all of whom opted for TFGT. Decisional conflict about TFGT choice (primary outcome) was not inferior in the IG compared with the UCG (noninferiority margin of -10; mean difference = 2.45; 95% confidence interval -2.87-7.76; P = 0.36). Costs per woman counseled in the IG were significantly lower (AUD$89) compared with the UCG (AUD$173; t(115) = 6.02; P < 0.001). CONCLUSION: A streamlined model of educating women newly diagnosed with breast cancer about TFGT seems to be a cost-effective way of delivering education while ensuring that women feel informed and supported in their decision making, thus freeing resources for other women to access TFGT.Genet Med 19 4, 448-456.

Referral of patients for pre-implantation genetic diagnosis: A survey of obstetricians.

BACKGROUND: Pre-implantation genetic diagnosis (PGD) is a molecular diagnostic technique in which embryos are tested for specific genetic abnormalities to enable the selection of those unaffected by the condition. Previous Australian evidence suggested that women who are not informed about PGD by their obstetrician feel disempowered about not being given this option. AIMS: This study aimed to explore obstetrician knowledge regarding PGD and identify barriers to referral. MATERIALS AND METHODS: An invitation to the study with a link to an online questionnaire was e-mailed by the Royal Australian and New Zealand College of Obstetricians and Gynaecologists to their members. RESULTS: In total, 372 practising obstetricians responded. Perceptions of their patients' financial status and ability to access PGD were identified as barriers to referral. There was variability in referral for PGD and/or genetic services according to the clinical scenario and in the perceived appropriateness of PGD for different indications. Obstetricians who had undergone professional development related to PGD were more likely to discuss PGD than those who had not (χ2 = 6.44; P < 0.01). CONCLUSIONS: The results highlight the need for additional training, development of educational resources and awareness of appropriate referral pathways to ensure that those couples who are eligible for PGD are informed.

Health professionals' evaluation of delivering treatment-focused genetic testing to women newly diagnosed with breast cancer.

Increasingly, women are offered genetic testing shortly after diagnosis of breast cancer to facilitate decision-making about treatment, often referred to as 'treatment-focused genetic testing' (TFGT). As understanding the attitudes of health professionals is likely to inform its integration into clinical care we surveyed professionals who participated in our TFGT randomized control study. Thirty-six completed surveys were received (response rate 59%), 15 (42%) health professionals classified as genetic and 21 (58%) as non-genetic. Mainly positive experiences with participating in the TFGT trial were reported. The high cost of testing and who could best deliver information about TGFT to the patient were raised as key constraints to implementation of TFGT in usual care. More non-genetic than genetic health professionals (44 vs 8%) preferred that the surgeon provide the information for decision-making about TFGT. While costs of TFGT itself and the time and effort of staff involved were perceived barriers, as testing costs become lower, it is expected that TFGT will become a routine part of standard clinical care for patients at high genetic risk in the near future.

Preferences regarding targeted education and risk assessment in people with a family history of major depressive disorder.

Genetic testing for susceptibility to major depressive disorder (MDD) is not available for clinical use at present. Given this, family history remains the best predictor for development of MDD, and family-history-based risk assessment and information about familial aspects of MDD may be useful to clients at increased risk for MDD attending for genetic counseling. This study uses a mixed-methods design to assess the information needs and preferences of people at increased familial risk for MDD. Telephone interviews were conducted with 23 individuals, who had at least one first-degree relative with MDD and were recruited through advertisements placed on depression education websites. The most preferred way to access depression information was via the internet (87 % of participants), although this preference may have been due to the internet-based recruitment method. The second most preferred dissemination strategy (56 %) was face-to-face delivery through a health professional, including genetic counselors. Individuals reported a need for information about etiology and development of MDD, reproductive decision-making, early detection of symptoms and risk-reducing strategies. Nearly all participants expressed an interest in risk assessment. The present study found evidence of a high level of interest for information targeted to people at increased familial risk for MDD. Genetic counselors are likely to be called upon increasingly to provide supportive counseling to assist clients at increased familial risk in interpreting and contextualizing such information once it becomes available.

Development and pilot testing of an online screening decision aid for men with a family history of prostate cancer.

OBJECTIVE: This study aimed to develop and pilot test an online screening decision aid (DA) for men with a family history of prostate cancer. METHODS: Eligible men (with no previous prostate cancer diagnosis) were recruited through relatives attending a urology outpatient clinic. Men evaluated the DA in two stages. First, they appraised a paper-based version using a questionnaire (n=22). Second, the same men were asked to reflect on an interactive web-based version via a semi-structured telephone interview (n=20). RESULTS: Men evaluated both forms of the DA positively. Of the paper-based version, the majority of participants found the DA useful (91%), and that it contained enough information to make a screening decision (73%). All participants reported that the online DA was easy to use and navigate. Most participants reported that a website was their preferred mode of receiving prostate cancer screening information (70%). CONCLUSION: The developed DA may represent the first online decision-making tool designed specifically for men with a family history prostate cancer that presents age and risk specific information to the user. PRACTICE IMPLICATIONS: Comprehensive evaluations of the efficacy and impact of educational interventions such as this are crucial to improve services for individuals making informed screening decisions.

Attitudes toward organ donation and donor behavior: a review of the international literature.

OBJECTIVE: To conduct a systematic review of published research that assessed the predictors of attitudes toward deceased organ donation, willingness to donate, and donor behavior. DATA SOURCES: MEDLINE, PreMEDLINE, PsycInfo, and the Cumulative Index to Nursing and Allied Health Literature were searched for the period from 1988 to 2009. STUDY SELECTION: Eligible studies included members of the general public (i.e., not transplant recipients, donor families, or health professionals) and used multivariate analyses for quantitative assessment of predictors. Data Extraction-The search identified 33 relevant studies. Owing to heterogeneity in populations and measures, results were summarized rather than subjected to meta-analysis. DATA SYNTHESIS: Research suggests that individuals who are younger, female, have higher education levels and socioeconomic status, hold fewer religious beliefs, have high knowledge levels, know others with positive attitudes, are more altruistic, and have fewer concerns about manipulation of the body of the deceased donor are more likely to have positive attitudes toward donation and are more willing to donate their organs. CONCLUSIONS: The review revealed the complexity of individuals' attitudes toward donation and the need for more sophisticated future studies of the interactions between the broader factors influencing donation (such as social norms and existing legislation in each country) and individual factors, such as attitudes and beliefs. (Progress in Transplantation.

Assessment of the content and process of genetic counseling: a critical review of empirical studies.

This article reviews studies that assessed the process and content of genetic counseling communication. A systematic search of the literature was undertaken of studies that audio- or videotaped genetic counseling sessions conducted by genetics health care providers and subjected them to communication analyses. A total of 18 studies (published in 34 articles) were identified that met the eligibility criteria. Studies show that providers speak more than clients, that a large proportion of communication is biomedical rather than psychosocial and that the teaching model of genetic counseling is widely implemented. Higher levels of counselor facilitation of understanding and empathic responses, lower levels of verbal dominance (ratio of counselor to client talk) and the provision of a summary letter of the consultation are associated with more positive client outcomes. Findings from these studies should be used as an evidence base for teaching and continuing education of genetic counseling providers.

Assessment of psychosocial outcomes in genetic counseling research: an overview of available measurement scales.

The aim of the present paper was to describe and evaluate many of the measurement scales currently used in genetic counseling outcomes research. A team of three researchers reviewed the available literature and selected a variety of validated instruments suitable for measurement of genetic counseling outcomes. There are numerous scales to assess each of the following outcomes among counselees: satisfaction with genetic counseling; knowledge; decision-making; psychological adjustment; coping; perceived personal control; perceptions of disease risk; and family communication about genetic risk. However, the strengths and limitations inherent to each instrument warrant careful consideration prior to implementation. In the genetic counseling context, scale selection should be undertaken with thought directed towards the characteristics of the research sample (e.g. levels of literacy, culture, medical condition), the practicalities of the research setting (e.g. available funding and resources, time restrictions, researcher expertise), the purpose of the research (i.e. the specific aspect of the genetic counseling experience to be studied), and the science underlying the scale (e.g. theoretical framework, psychometric properties).

Genetic services for men: the preferences of men with a family history of prostate cancer.

PURPOSE: Men have a lower uptake of genetic services than women; however, the specific needs and preferences of men at risk of genetic conditions other than hereditary breast ovarian cancer are not known. We ascertain the information preferences of men with a family history of prostate cancer. METHODS: Unaffected men and their partners were administered a written questionnaire. RESULTS: Responses were received from 280 men (response rate: 59.2%) and 174 partners (response rate: 74%). Most men (59.6%) reported having insufficient information about their risk and wanted further information about personal risk (93.2%) and risk management (93.6%). Strikingly, 56.3% preferred to receive information related only to positive outcomes. Urologists were the preferred source of information, but there was considerable interest in a multidisciplinary service approach significantly associated with the number of affected relatives (odds ratio = 1.94, P < .002). Partners' level of concern was not associated with interest in multidisciplinary services, satisfaction with information, or support received. CONCLUSIONS: Delivering services to men at risk will require a multifaceted approach by primary care providers and specialists. Challenges include meeting men's expectations in the face of uncertain medical knowledge, engaging those at high risk in multidisciplinary services, and delivering tailored information to those at lower risk.

Impact of familial adenomatous polyposis on young adults: attitudes toward genetic testing, support, and information needs.

PURPOSE: The study assessed views concerning genetic testing and information and support needs among young adults aged 18 to 35 years with a diagnosis of or at risk of developing familial adenomatous polyposis. METHODS: A total of 88 participants were recruited through Hereditary Bowel Cancer Registries and assessed using self-administered questionnaires. RESULTS: The average age of participants was 28 years, and the average age at the time of their last genetic consultation was 23 years. Although 75% would consider prenatal genetic testing, only 21% would consider termination of an affected pregnancy. Sixty-one percent selected "at birth" or "early childhood" as the preferred age for genetic testing of offspring. Participants' highest areas of unmet support needs were with regard to anxiety about their children having familial adenomatous polyposis (39%) and fear of developing cancer (28%). CONCLUSION: The parental desire to test children before it is clinically indicated may be a source of distress and create conflict with genetic services. These findings demonstrate that familial adenomatous polyposis may significantly impact young adults, with many having unmet support needs. The length of time since the last genetic consultation and the young age at which these consultations took place suggest that clinics should consider a means of regular follow-up to address these unmet needs.

Evaluation of the needs and concerns of partners of women at high risk of developing breast/ovarian cancer.

This exploratory study investigates the experience of partners of women at high risk of developing breast/ovarian cancer and reports on the partners' views concerning their relationship, communication, future planning, children and childbearing, involvement in decision-making regarding screening and prophylactic measures, and information and support needs. In-depth interviews were conducted with 15 partners. Of these, seven were partners of women who were BRCA1/2 mutation carriers, five were partners of women with unknown mutation status, and three were partners of women who were non-carriers. None of the women had a previous diagnosis of breast or ovarian cancer. Partners of carriers and women with unknown mutation status were found to be more distressed than partners of non-carriers, with partners of mutation carriers reporting the most difficulties. Factors associated with better adjustment and coping for partners included dealing with this situation as a team with their wife, greater involvement in decision-making, satisfaction with their supportive roles and being optimistic. Decision-making difficulties in relation to prophylactic measures, concerns about their children possibly being at increased cancer risk, as well as the need to receive information directly from health professionals and the wish to meet other partners were also discussed.