Systematic review of the uptake and outcomes from returning secondary findings to adult participants in research genomic testing.

The increasing use of genomic sequencing in research means secondary findings (SF) is more frequently detected and becoming a more pressing issue for researchers. This is reflected by the recent publication of multiple guidelines on this issue, calling for researchers to have a plan for managing SF prior to commencing their research. A deeper understanding of participants' experiences and outcomes from receiving SF is needed to ensure that the return of SF is conducted ethically and with adequate support. This review focuses on the uptake and outcomes of receiving actionable SF for research participants. This review included studies from January 2010 to January 2023. Databases searched included Medline, Embase, PsycINFO, and Scopus. Of the 3903 studies identified, 29 were included in the analysis. The uptake of SF ranged between 20% and 97%, and outcomes were categorized into psychological, clinical, lifestyle and behavioral, and family outcomes. The results indicate there is minimal psychological impact from receiving SF. Almost all participants greatly valued receiving SF. These findings highlight considerations for researchers when returning results, including the importance of involving genetic health professionals in consenting, results return process, and ensuring continuity of care by engaging healthcare providers.

Development and evaluation of a novel educational program for providers on the use of polygenic risk scores.

PURPOSE: This study aimed to develop an online educational program for using polygenic risk score (PRS) for breast and ovarian cancer risk assessments and to evaluate the impact on the attitudes, confidence, knowledge, and preparedness of genetic health care providers (GHPs). METHODS: The educational program comprises an online module that covers the theoretical aspects of PRS and a facilitated virtual workshop with prerecorded role-plays and case discussions. Data were collected in pre- and posteducation surveys. Eligible participants were GHPs working in Australian familial cancer clinics registered to recruit patients for a breast and ovarian cancer PRS clinical trial (n = 12). RESULTS: A total of 124 GHPs completed the PRS education, of whom 80 (64%) and 67 (41%) completed the pre- and posteducation surveys, respectively. Before education, GHPs reported limited experience, confidence, and preparedness using PRS, but they recognized its potential benefits. After education, GHPs indicated improved attitudes (P ≤ .001), confidence (P ≤ .001), knowledge (P ≤ .001), and preparedness (P ≤ .001) to use PRS. Most GHPs thought that the program entirely met their learning needs (73%) and was completely relevant to their clinical practice (88%). GHPs identified PRS implementation barriers, including limited funding models, diversity issues, and need for clinical guidelines. CONCLUSION: Our education program improved GHP attitudes, confidence, knowledge, and preparedness for using PRS/personalized risk and provides a framework for the development of future programs.

Models of communication for polygenic scores and associated psychosocial and behavioral effects on recipients: A systematic review.

PURPOSE: This study aimed to systematically review current models for communicating polygenic scores (PGS) and psycho-behavioral outcomes of receiving PGSs. METHODS: Original research on communicating PGSs and reporting on psycho-behavioral outcomes was included. Search terms were applied to 5 databases and were limited by date (2009-2021). RESULTS: In total, 28 articles, representing 17 studies in several disease settings were identified. There was limited consistency in PGS communication and evaluation/reporting of outcomes. Most studies (n = 14) presented risk in multiple ways (ie, numerically, verbally, and/or visually). Three studies provided personalized lifestyle advice and additional resources. Only 1 of 17 studies reported using behavior change theory to inform their PGS intervention. A total of 8 studies found no evidence of long-term negative psychosocial effects up to 12 months post result. Of 14 studies reporting on behavior, 9 found at least 1 favorable change after PGS receipt. When stratified by risk, 7 out of 9 studies found high PGS was associated with favorable changes including lifestyle, medication, and screening. Low-risk PGS was not associated with maladaptive behaviors (n = 4). CONCLUSION: PGS has the potential to benefit health behavior. High variability among studies emphasizes the need for developing standardized guidelines for communicating PGSs and evaluating psycho-behavioral outcomes. Our findings call for development of best communication practices and evidence-based interventions informed by behavior change theories.

Human Genetics Society of Australasia Position Statement: Use of Polygenic Scores in Clinical Practice and Population Health.

Considerable progress continues to be made with regards to the value and use of disease associated polygenic scores (PGS). PGS aim to capture a person's genetic liability to a condition, disease, or a trait, combining information across many risk variants and incorporating their effect sizes. They are already available for clinicians and consumers to order in Australasia. However, debate is ongoing over the readiness of this information for integration into clinical practice and population health. This position statement provides the viewpoint of the Human Genetics Society of Australasia (HGSA) regarding the clinical application of disease-associated PGS in both individual patients and population health. The statement details how PGS are calculated, highlights their breadth of possible application, and examines their current challenges and limitations. We consider fundamental lessons from Mendelian genetics and their continuing relevance to PGS, while also acknowledging the distinct elements of PGS. Use of PGS in practice should be evidence based, and the evidence for the associated benefit, while rapidly emerging, remains limited. Given that clinicians and consumers can already order PGS, their current limitations and key issues warrant consideration. PGS can be developed for most complex conditions and traits and can be used across multiple clinical settings and for population health. The HGSA's view is that further evaluation, including regulatory, implementation and health system evaluation are required before PGS can be routinely implemented in the Australasian healthcare system.

Pharmacogenomic testing: perception of clinical utility, enablers and barriers to adoption in Australian hospitals.

BACKGROUND: Despite healthcare professionals (HCP) endorsing the clinical utility of pharmacogenomics testing, use in clinical practice is limited. AIMS: To assess HCP' perceptions of pharmacogenomic testing and identify barriers to implementation. METHODS: HCP involved in prescribing decisions at three hospitals in Sydney, Australia, were invited to participate. The online survey assessed perceptions of pharmacogenomic testing, including: (i) demographic and practice variables; (ii) use, knowledge and confidence; (iii) perceived benefits; (iv) barriers to implementation; and (v) operational and/or system changes and personnel required to implement on site. RESULTS: HCP were predominantly medical practitioners (75/107) and pharmacists (25/107). HCP perceived pharmacogenomic testing was beneficial to identify reasons for drug intolerance (85/95) and risk of side-effects (86/95). Although testing was considered relevant to their practice (79/100), few HCP (23/100) reported past or intended future use (26/100). Few HCP reported confidence in their ability to identify indications for pharmacogenomic testing (14/107), order tests (19/106) and communicate results with patients (16/107). Lack of clinical practice guidelines (62/79) and knowledge (54/77) were identified as major barriers to implementation of pharmacogenomics. Comprehensive reimbursement for testing and clinical practice guidelines, alongside models-of-care involving multidisciplinary teams and local clinical champions were suggested as strategies to facilitate implementation of pharmacogenomic testing into practice. CONCLUSIONS: Pharmacogenomic testing was considered important to guide drug selection and dosing decisions. However, limited knowledge, low confidence and an absence of guidelines impede the use of pharmacogenomic testing. Establishment of local resources including multidisciplinary models-of-care was suggested to facilitate implementation of pharmacogenomics.

Polygenic risk in familial breast cancer: Changing the dynamics of communicating genetic risk.

Hereditary breast cancer is associated with known genetic changes: either variants that affect function in a few rare genes or an ever-increasing number of common genomic risk variants, which combine to produce a cumulative effect, known as a polygenic risk (PR) score. While the clinical validity and utility of PR scores are still being determined, the communication of PR is a new challenge for genetic health professionals. This study investigated how PR scores are discussed in the familial cancer clinic compared with a previous study assessing the communication of monogenic risk (MR) for breast cancer. Sixty-five PR consultations between genetic health professionals and women at familial risk of breast cancer were audiotaped, transcribed, and coded using a methodology adapted from the MR study. Analysis of consultations shows that while there were similarities in communicating MR and PR, the complexity and novelty of the polygenic information influenced the style of counseling used by genetic health professionals toward a teaching model of genetic counseling, rather than a patient-centered approach. In particular, compared to MR consultations, in PR consultations significantly fewer counselees (a) were asked about their reasons for attending genetic counseling; or (b) had their information preferences, decision-making style, medical knowledge, understanding, or concerns checked. In conclusion, it is anticipated that PR scores will become part of standard clinical practice. Thus, it will be important for all genetic health professionals to be appropriately educated so that they can tailor their communication to meet patient needs.

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.

Knowledge, views and expectations for cancer polygenic risk testing in clinical practice: A cross-sectional survey of health professionals.

Polygenic risk scores (PRS) are becoming increasingly available in clinical practice to evaluate cancer risk. However, little is known about health professionals' knowledge, attitudes, and expectations of PRS. An online questionnaire was distributed by relevant health professional organisations predominately in Australia, Canada and the US to evaluate health professionals' knowledge, views and expectations of PRS. Eligible participants were health professionals who provide cancer risk assessments. Results from the questionnaire were analysed descriptively and content analysis was undertaken of free-text responses. In total, 105 health professionals completed the questionnaire (genetic counsellors 84%; oncologists 6%; clinical geneticists 4%; other 7%). Although responses differed between countries, most participants (61%) had discussed PRS with patients, 20% had ordered a test and 14% had returned test results to a patient. Confidence and knowledge around interpreting PRS were low. Although 69% reported that polygenic testing will certainly or likely influence patient care in the future, most felt unprepared for this. If scaled up to the population, 49% expect that general practitioners would have a primary role in the provision of PRS, supported by genetic health professionals. These findings will inform the development of resources to support health professionals offering polygenic testing, currently and in the future.

Finding the five-year window: A qualitative study examining young women's decision-making and experience of using tamoxifen to reduce BRCA1/2 breast cancer risk.

OBJECTIVE: Tamoxifen has been demonstrated to reduce breast cancer risk in high-risk, premenopausal women. Yet, very few young women with hereditary breast and ovarian cancer syndrome in Australia use tamoxifen, despite this being a less-invasive option compared to risk-reducing mastectomy. This study aims to examine young women's decision-making about and experience of taking tamoxifen to reduce their breast cancer risk. METHODS: Young women with a BRCA1/2 mutation participated in semi-structured qualitative interviews, recruited mainly from a metropolitan clinical genetics service. Data were analysed using an inductive, team-based approach to thematic analysis. RESULTS: Forty interviews with women aged 20-40 years with a BRCA1/2 mutation were conducted. Eleven women could not recall discussing tamoxifen with their healthcare provider or were too young to commence cancer risk management. Twenty-three women chose not to use tamoxifen because it is contraindicated for pregnancy or because it did not offer immediate and great enough risk reduction compared to bilateral risk-reducing mastectomy. Six women who were definite about not wanting to have children during the following 5-year period chose to use tamoxifen, and most experienced none or transient side effects. CONCLUSIONS: Decision-making about tamoxifen was nuanced and informed by considerations characteristic of young adulthood, especially childbearing. Therefore, clinical discussions about tamoxifen with young women with a BRCA1/2 mutation must include consideration of their reproductive plans.

Education in youth-friendly genetic counseling.

Genetic counselors have long recognized the challenges of working with adolescents and young adults (AYA) and their families. In 2010, a framework of Youth-friendly Genetic Counseling was developed by an expert reference group with the aim to improve both care for AYAs and the experience of health professionals delivering that care. Subsequently, an education workshop was developed aimed to upskill genetic health professionals in youth-friendly genetic counseling. The workshop was piloted with genetic counselors in Australia and New Zealand. A purpose designed, pre- and post-workshop survey and post-workshop focus group was utilized for evaluation. Mean confidence scores increased pre- and post-workshop. Participants also demonstrated increases in knowledge regarding: adolescent development; developmental theory; social factors impacting on health; the needs of young people; practice challenges; youth-friendly engagement, communication, consent and confidentiality; practice approaches; principles of adolescent healthcare; ethical issues; and available services and resources. Focus group data revealed several themes relating to practice challenges, learning gains, barriers, and enablers to clinical translation and workshop feedback. Results demonstrate utility of the workshop in up-skilling genetic health professionals in the provision of youth-friendly genetic counseling. Consideration of adaptation and sustainability, by embedding this theoretical and skills-based workshop as a module within genetic counseling education, is required to ensure practice competence and the best health outcomes for young people and their families.

Social media usage in family communication about genetic information: 'I no longer speak with my sister but she needed to know'.

The use of social media has become a ubiquitous form of communication. Little is known about whether social media is used in families to assist with the communication of genetic information. This study aimed to understand if and why individuals use social media to communicate genetic information to at-risk relatives. Individuals with either a pathogenic variant in a cancer-predisposing gene or a heterozygous pathogenic variant in an autosomal or X-linked recessive gene were surveyed about communicating genetic information to their at-risk relatives and their use of social media to assist this process. Surveys were sent to 323 individuals from a reproductive carrier screening program and 250 individuals from a familial cancer center. The 128 responses (response rate 25.2%) showed that while most participants (79.0%) did not use social media to communicate genetic information, those that did use social media (21.0%) found it to be helpful as it was easy, accessible and allowed individuals to overcome communication barriers. Genetic professionals should be aware that social media is being used by individuals to assist family communication about genetic information and should discuss this method of communication with individuals who are faced with communicating genetic information with their family.

Influence of lived experience on risk perception among women who received a breast cancer polygenic risk score: 'Another piece of the pie'.

Polygenic risk scores (PRS) are personalized assessments of disease risk based on the cumulative effect of common low-risk genetic variants. PRS have been shown to accurately predict women's breast cancer risk and are likely to be incorporated into personalized breast cancer risk management programs. However, there are few studies investigating the individual impact of receiving a breast cancer PRS. Existing studies have not demonstrated significant changes in perceived risk or risk management behaviors after receipt of polygenic risk information. The aim of this qualitative study was to explore how women with a family history of breast cancer construct breast cancer risk perceptions after receipt of a breast cancer PRS. Unaffected women with a family history of breast cancer who had not previously received genetic counseling regarding their breast cancer risk were invited to participate in this study. In-depth, semi-structured interviews were conducted with 20 women who attended a familial cancer clinic in the Australian states of Victoria and Tasmania. Data were analyzed using an inductive thematic approach. Women's lived experience played a significant role in the construction and maintenance of their breast cancer risk perception. Women's pre-existing risk perceptions were informed by their family history and their knowledge that breast cancer is a multifactorial disease. Knowing that breast cancer is a multifactorial disease enabled most women to integrate genetic information with their pre-existing notions of risk. Women reported that the information they received was consistent with their existing notions of personal risk and screening advice. Therefore, the PRS did not lead to a change in perceived risk or risk management behaviors for most women. The results of this study provide insight into how polygenic risk information is integrated with pre-existing notions of risk, which will inform its implementation into clinical practice.

Professional regulation for Australasian genetic counselors.

As a result of the ongoing global expansion of genetic counseling, the need to formalize a system of professional regulation for genetic counselors was identified in Australasia. In June 2017, under the auspices of the Human Genetics Society of Australasia (HGSA), a working party was convened. The purpose of the working party was to provide strategic leadership for the profession of Australasian genetic counselors with a goal to formalize a national regulatory framework for genetic counselors across both Australian and New Zealand jurisdictions. This was ultimately achieved in Australia through full membership with the National Alliance of Self-Regulating Health Professions (NASRHP) while the profession of genetic counseling in New Zealand is utilizing this framework to establish their regulation pathway. Regulation has a number of implications for genetic counselors, their employers, and the wider community, with the primary purpose of regulation being protection of the public from harm. This paper details the process of formalizing self-regulation for genetic counselors in Australasia, by defining professional regulation; outlining the purpose of regulation and the status of regulation for genetic counselors in Australasia and internationally, as well as health professionals more broadly; exploring the challenges of establishing regulation in Australasia; and the next steps for regulation in Australasia. Through detailing this process, the intention is to provide a framework to support genetic counseling colleagues internationally as well as other health professions in Australasia to explore and achieve regulation through their respective jurisdiction.

Clinical applications of polygenic breast cancer risk: a critical review and perspectives of an emerging field.

Polygenic factors are estimated to account for an additional 18% of the familial relative risk of breast cancer, with those at the highest level of polygenic risk distribution having a least a twofold increased risk of the disease. Polygenic testing promises to revolutionize health services by providing personalized risk assessments to women at high-risk of breast cancer and within population breast screening programs. However, implementation of polygenic testing needs to be considered in light of its current limitations, such as limited risk prediction for women of non-European ancestry. This article aims to provide a comprehensive review of the evidence for polygenic breast cancer risk, including the discovery of variants associated with breast cancer at the genome-wide level of significance and the use of polygenic risk scores to estimate breast cancer risk. We also review the different applications of this technology including testing of women from high-risk breast cancer families with uninformative genetic testing results, as a moderator of monogenic risk, and for population screening programs. Finally, a potential framework for introducing testing for polygenic risk in familial cancer clinics and the potential challenges with implementing this technology in clinical practice are discussed.

Uptake of polygenic risk information among women at increased risk of breast cancer.

Polygenic risk scores (PRSs) are increasingly being implemented to assess breast cancer risk. This study aimed to assess and determine factors associated with uptake of PRS among women at increased risk of breast cancer for whom genetic testing to date had been uninformative. Participants were recruited from the Variants in Practice study from which breast cancer PRS had been calculated. Four hundred women were notified by letter of the availability of their PRS and invited to complete a self-administered survey comprising several validated scales. Considering non-participants, uptake of PRS was between 61.8% and 42.1%. Multivariate logistic regression identified that women were more likely to receive their PRS if they reported greater benefits (odds ratio [OR] = 1.17, P = .011) and fewer barriers to receiving their PRS (OR = 0.80, P = .007), had completed higher level education (OR = 3.32, P = .004), and did not have daughters (0.29, P = .006). Uptake of breast cancer PRS varied according to several testing- and patient-related factors. Knowledge of these factors will facilitate the implementation of polygenic testing in clinical practice and support informed decision making by patients.

Population-based genetic testing of asymptomatic women for breast and ovarian cancer susceptibility.

PURPOSE: The identification of carriers of hereditary breast and ovarian cancer (HBOC) gene variants through family cancer history alone is suboptimal, and most population-based genetic testing studies have been limited to founder mutations in high-risk populations. Here, we determine the clinical utility of identifying actionable variants in a healthy cohort of women. METHODS: Germline DNA from a subset of healthy Australian women participating in the lifepool project was screened using an 11-gene custom sequencing panel. Women with clinically actionable results were invited to attend a familial cancer clinic (FCC) for post-test genetic counseling and confirmatory testing. Outcomes measured included the prevalence of pathogenic variants, and the uptake rate of genetic counseling, risk reduction surgery, and cascade testing. RESULTS: Thirty-eight of 5908 women (0.64%) carried a clinically actionable pathogenic variant. Forty-two percent of pathogenic variant carriers did not have a first-degree relative with breast or ovarian cancer and 89% pursued referral to an FCC. Forty-six percent (6/13) of eligible women pursued risk reduction surgery, and the uptake rate of cascade testing averaged 3.3 family members per index case. CONCLUSION: Within our cohort, HBOC genetic testing was well accepted, and the majority of high-risk gene carriers identified would not meet eligibility criteria for genetic testing based on their existing family history.

Men's experiences of recontact about a potential increased risk of prostate cancer due to Lynch Syndrome: "Just another straw on the stack".

The practice of recontacting patients to provide new health information is becoming increasingly common in clinical genetics, despite the limited research to evidence the patient experience. We explored how men with Lynch Syndrome (LS) understand and experience being recontacted about a potential increased risk of prostate cancer. Sixteen men with LS (Meanage 51 years) were recruited from an Australian screening study to undergo a semi-structured interview. A modified grounded theory approach was used to guide data collection and thematic analysis. Qualitative coding was shared by the research team to triangulate analysis. The practice of recontact was viewed by participants as acceptable and was associated with minimal emotional distress. The majority of men understood that they may be above population risk of prostate cancer, although evidence was still emerging. Men reported high engagement with personal and familial health, including regular screening practices and familial risk communication. Findings suggest that men's carrier status and beliefs about the actionability of the new cancer risk information influence their response to recontact. Recontact practices that include the offer of risk management strategies may lead to improved patient outcomes (e.g., reduced cancer worry and increased health engagement), if perceived as valuable by recipients.

The PiGeOn project: protocol for a longitudinal study examining psychosocial, behavioural and ethical issues and outcomes in cancer tumour genomic profiling.

BACKGROUND: Genomic sequencing in cancer (both tumour and germline), and development of therapies targeted to tumour genetic status, hold great promise for improvement of patient outcomes. However, the imminent introduction of genomics into clinical practice calls for better understanding of how patients value, experience, and cope with this novel technology and its often complex results. Here we describe a protocol for a novel mixed-methods, prospective study (PiGeOn) that aims to examine patients' psychosocial, cognitive, affective and behavioural responses to tumour genomic profiling and to integrate a parallel critical ethical analysis of returning results. METHODS: This is a cohort sub-study of a parent tumour genomic profiling programme enrolling patients with advanced cancer. One thousand patients will be recruited for the parent study in Sydney, Australia from 2016 to 2019. They will be asked to complete surveys at baseline, three, and five months. Primary outcomes are: knowledge, preferences, attitudes and values. A purposively sampled subset of patients will be asked to participate in three semi-structured interviews (at each time point) to provide deeper data interpretation. Relevant ethical themes will be critically analysed to iteratively develop or refine normative ethical concepts or frameworks currently used in the return of genetic information. DISCUSSION: This will be the first Australian study to collect longitudinal data on cancer patients' experience of tumour genomic profiling. Findings will be used to inform ongoing ethical debates on issues such as how to effectively obtain informed consent for genomic profiling return results, distinguish between research and clinical practice and manage patient expectations. The combination of quantitative and qualitative methods will provide comprehensive and critical data on how patients cope with 'actionable' and 'non-actionable' results. This information is needed to ensure that when tumour genomic profiling becomes part of routine clinical care, ethical considerations are embedded, and patients are adequately prepared and supported during and after receiving results. TRIAL REGISTRATION: Not required for this sub-study, parent trial registration ACTRN12616000908437 .

The PiGeOn project: protocol of a longitudinal study examining psychosocial and ethical issues and outcomes in germline genomic sequencing for cancer.

BACKGROUND: Advances in genomics offer promise for earlier detection or prevention of cancer, by personalisation of medical care tailored to an individual's genomic risk status. However genome sequencing can generate an unprecedented volume of results for the patient to process with potential implications for their families and reproductive choices. This paper describes a protocol for a study (PiGeOn) that aims to explore how patients and their blood relatives experience germline genomic sequencing, to help guide the appropriate future implementation of genome sequencing into routine clinical practice. METHODS: We have designed a mixed-methods, prospective, cohort sub-study of a germline genomic sequencing study that targets adults with cancer suggestive of a genetic aetiology. One thousand probands and 2000 of their blood relatives will undergo germline genomic sequencing as part of the parent study in Sydney, Australia between 2016 and 2020. Test results are expected within12-15 months of recruitment. For the PiGeOn sub-study, participants will be invited to complete surveys at baseline, three months and twelve months after baseline using self-administered questionnaires, to assess the experience of long waits for results (despite being informed that results may not be returned) and expectations of receiving them. Subsets of both probands and blood relatives will be purposively sampled and invited to participate in three semi-structured qualitative interviews (at baseline and each follow-up) to triangulate the data. Ethical themes identified in the data will be used to inform critical revisions of normative ethical concepts or frameworks. DISCUSSION: This will be one of the first studies internationally to follow the psychosocial impact on probands and their blood relatives who undergo germline genome sequencing, over time. Study results will inform ongoing ethical debates on issues such as informed consent for genomic sequencing, and informing participants and their relatives of specific results. The study will also provide important outcome data concerning the psychological impact of prolonged waiting for germline genomic sequencing. These data are needed to ensure that when germline genomic sequencing is introduced into standard clinical settings, ethical concepts are embedded, and patients and their relatives are adequately prepared and supported during and after the testing process.

Making Sense of SNPs: Women's Understanding and Experiences of Receiving a Personalized Profile of Their Breast Cancer Risks.

Genome wide association studies have identified a number of common genetic variants - single nucleotide polymorphisms (SNPs) - that combine to increase breast cancer risk. SNP profiling may enhance the accuracy of risk assessment and provides a personalized risk estimate. SNP testing for breast cancer risks may supplement other genetic tests in the future, however, before it can be implemented in the clinic we need to know how it will be perceived and received. Semi-structured qualitative interviews were conducted with 39 women who had previously had a breast cancer diagnosis and undergone BRCA1/2 testing, participated in the Variants in Practice (ViP) study and received personalized risk (SNP) profiles. Interviews explored their understanding and experiences of receiving this SNP information. Women reported feeling positive about receiving their personalized risk profile, because it: provided an explanation for their previous diagnosis of cancer, vindicated previous risk management decisions and clarified their own and other family members' risks. A small group was initially shocked to learn of the increased risk of a second primary breast cancer. This study suggests that the provision of personalized risk information about breast cancer generated by SNP profiling is understood and well received. However, a model of genetic counseling that incorporates monogenic and polygenic genetic information will need to be developed prior to clinical implementation.