Genetic counseling and testing for females at elevated risk for breast cancer: Protocol for the randomized controlled trial of the Know Your Risk intervention.

BACKGROUND: Genetic counseling and testing have an important role in the care of patients at elevated risk for breast cancer. However, conventional pre- and post-test genetic counseling is labor and time intensive, less accessible for patients living outside major urban centers, and impractical on a large scale. A patient-driven approach to genetic counseling and testing may increase access, improve patients' experiences, affect efficiency of clinical practice, and help meet workforce demand. The objective of this 2-arm randomized controlled trial is to determine the efficacy of Know Your Risk (KYR), a genetic counseling patient preference intervention. METHODS: Females (n = 1000) at elevated risk (>20% lifetime) for breast cancer will be randomized to the KYR intervention or conventional genetic counseling. The study will provide comprehensive assessment of breast cancer risk by multigene panel testing and validated polygenic risk score. Primary outcome is adherence to National Comprehensive Cancer Network guidelines for a clinical encounter every 6-12 months and an annual mammogram (breast MRI if recommended) determined by medical record review. Secondary outcomes include adherence to other recommended cancer screening tests determined by medical record review and changes in breast cancer knowledge, perception of risk, post-test/counseling distress, and satisfaction with counseling by completion of three surveys during the study. Study aims will be evaluated for non-inferiority of the KYR intervention compared to conventional genetic counseling. CONCLUSION: If efficacious, the KYR intervention has the potential to improve patients' experience and may change how genetic counseling is delivered, inform best practices, and reduce workforce burden. TRIAL REGISTRATION: ClinicalTrials.govNCT05325151.

Satisfaction With Clinician-Led Germline Genetic Counseling in Patients With Prostate Cancer.

PURPOSE: Indications for germline testing in prostate cancer patients have expanded substantially over the past decade. With a near-universal shortage of genetic counselors and increasing demand, increased access to genetic counseling is crucial. We sought to prospectively implement and assess a clinician-led approach to genetic counseling and testing. MATERIALS AND METHODS: Patients with metastatic or localized prostate cancer meeting National Comprehensive Cancer Network® criteria for consideration of genetic testing were offered pre-test genetic counseling by their urologist or medical oncologist as part of their routine clinical care and concurrently approached for enrollment in the Germline Genetics in Prostate Cancer Study. Consented patients filled out a post-counseling survey using validated instruments to assess the quality of counseling. For patients who elected to undergo genetic testing, an additional validated questionnaire was completed following disclosure of results. The primary outcome was the proportion of patients undergoing testing, with a target >60% of patients. The secondary outcome was overall satisfaction with counseling, with a target >85% of patients. RESULTS: A total of 275 patients enrolled, and 203 patients elected to undergo genetic testing. Post-counseling surveys were obtained from 265 patients, and post-genetic testing surveys were obtained from 132 patients. Patient satisfaction was high, with 98% of patients reporting being satisfied with the overall quality of pre-test counseling, and 74% of patients elected to undergo genetic testing. CONCLUSIONS: These results support the effectiveness of clinician-led genetic counseling in prostate cancer. With clinician training, this approach can be utilized to expand access to appropriate germline genetic testing.

Factors associated with referral and completion of genetic counseling in women with epithelial ovarian cancer.

OBJECTIVE: The National Comprehensive Cancer Network recommends that all women diagnosed with epithelial ovarian cancer undergo genetic testing, as the diagnosis of pathogenic variants may inform cancer survival and impact treatment options. The objective of this study was to assess factors associated with referral to genetic counseling in women with epithelial ovarian cancer. METHODS: A retrospective cohort study identified women with epithelial ovarian cancer from 2012 to 2017 at Massachusetts General Hospital and North Shore Medical Center, a community hospital affiliated with Massachusetts General Hospital. Multivariate logistic regression evaluated how race, age, stage, year of diagnosis, insurance status, family history of breast or ovarian cancer, and language relates to the receipt of genetic counseling. RESULTS: Of the total 276 women included, 73.9% were referred for genetic screening, of which 90.7% attended a genetic counseling visit. Older women were less likely to undergo genetic counseling (age ≥70 years: OR 0.26, 95% CI 0.07-0.94, p=0.04). Women who died within 365 days of initial oncology consult rarely reached a genetic counselor (OR 0.05, 95% CI 0.01-0.24, p<0.001). Women with a family history of breast or ovarian cancer were more likely to undergo counseling (OR 3.27, 95% CI 1.74-6.15, p<0.001). There was no difference in receipt of genetic counseling by race, stage, year of diagnosis, insurance status, or language. CONCLUSION: Older women with epithelial ovarian cancer and those who died within 1 year of initiation of care were less likely to undergo recommended genetic counseling. Race, insurance status, and language were not identified as predictive factors, although we were limited in this assessment by small sample size.

Coordination of Genetic Care: More Important and Complicated Than it Seems.

Families with hereditary risk for developing malignancy benefit from organized, coordinated care by a genetics professional. This report presents a case illustrating the potential errors that can occur when genetic care is fragmented and not coordinated, including ordering too much or not enough genetic testing, failing to communicate with the family who is at potential genetic risk, failing to communicate what the results of testing mean, and failing to recommend appropriate care, which may lead to psychosocial distress and late-detected cancers. This case highlights the complexities of genetic care and why management by a genetics professional results in more fiscally responsible care, appropriate genetic testing, and comprehensive care for all family members at risk.

Role play for genetic counseling learning: Value and students perceptions.

BACKGROUND: Performing genetic counseling is one of the tasks of every paediatrician. This assumes prior training during the residency. AIM: To assess the impact of role-play (RP) for training of paediatric residents in genetic counseling and participants' perception. METHODS: Repetitive cross-sectional evaluation study. During two RP sessions, two residents played the role of the parents of a patient with cystic fibrosis, and another the role of the doctor. Residents had an evaluation by standardized patient exercises immediately before and after the session. Test scores were compared by the Wilcoxon rank test for associated samples. A satisfaction questionnaire was completed by the participants anonymously. RESULTS: Post-test scores were better than pre-test scores overall (p = 0.002) and for items in the cognitive domain (p = 0.002). Of the 12 participants, only one had had previous training in genetic counseling. All participants were satisfied with the learning and felt that it would change the way they practice. All participants thought they could do genetic counseling autonomously, but nine of them wanted to have other RP sessions on the same theme. Only one participant found the session stressful and all wanted to multiply this type of sessions for other learning. CONCLUSION: RP is an effective and well-accepted means for genetic counseling training. It should be integrated with paediatric resident training.

Implementation of a quality improvement project for universal genetic testing in women with ovarian cancer.

OBJECTIVE: The National Comprehensive Cancer Network recommends all women with ovarian cancer be offered genetic testing. Despite a decade of endorsement, many oncology practitioners have yet to make this a part of routine practice. Referral to genetic counseling and completion of genetic testing among patients at substantial risk of germline mutations are significantly lacking, adversely affecting patient care and squandering an opportunity to maximize cancer prevention efforts. This project determined the impact and feasibility of implementing a basic model for universal referral to genetic counseling and completion of genetic testing in women with a diagnosis of ovarian cancer in an academic gynecology oncology practice with access to electronic health records (EHRs). METHODS: Patients diagnosed with ovarian cancer from January 2008 to November 2013 were retrospectively reviewed to determine the baseline referral rate for genetic counseling and testing completion in our practice. Implementation of a process change model combining provider training, patient education, enhanced electronic health record documentation and improved patient appointment scheduling strategies were implemented. We then prospectively collected data on all newly diagnosed ovarian cancer patients that had not already undergone genetic testing presenting from December 1, 2013 to November 30, 2016. RESULTS: Genetic referral rates, genetic counseling and testing completion rates were markedly improved. Pre-implementation our genetic testing rate was 27% and post implementation our testing rate was 82% (p-value≤0.001). CONCLUSIONS: Low cost interventions that target education of both providers and patients regarding the importance of genetic testing along with utilization of the EHR and streamlined patient appointment services can significantly increase rates of genetic testing completion.

Patient Decisions to Receive Secondary Pharmacogenomic Findings and Development of a Multidisciplinary Practice Model to Integrate Results Into Patient Care.

Whole exome sequencing (WES) has the potential of identifying secondary findings that are predictive of poor pharmacotherapy outcomes. The purpose of this study was to investigate patients' wishes regarding the reporting of secondary pharmacogenomic findings. WES results (n = 106 patients) were retrospectively reviewed to determine the number of patients electing to receive secondary pharmacogenomic results. Phenotypes were assigned based on Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. The percent of patients with a predicted phenotype associated with a gene-based CPIC dosing recommendation was determined. Ninety-nine patients (93.4%) elected to receive secondary pharmacogenomic findings. For each gene-drug pair analyzed, the number of patients with an actionable phenotype ranged from two (2%) to 43 patients (43.4%). Combining all gene-drug pairs, 84 unique patients (84.8%) had an actionable phenotype. A prospective multidisciplinary practice model was developed for integrating secondary pharmacogenomic findings into clinical practice. Our model highlights a unique collaboration between physician-geneticists, pharmacists, and genetic counselors.

Multi-disciplinary summit on genetics services for women with gynecologic cancers: A Society of Gynecologic Oncology White Paper.

OBJECTIVE: To assess current practice, advise minimum standards, and identify educational gaps relevant to genetic screening, counseling, and testing of women affected by gynecologic cancers. METHODS: The Society of Gynecologic Oncology (SGO) organized a multidisciplinary summit that included representatives from the American College of Obstetricians and Gynecologists (ACOG), the American Society Clinical Oncology (ASCO), the National Society of Genetic Counselors (NSGC), and patient advocacy groups, BrightPink and Facing our Risk of Cancer Empowered (FORCE). Three subject areas were discussed: care delivery models for genetic testing, barriers to genetic testing, and educational opportunities for providers of genetic testing. RESULTS: The group endorsed current SGO, National Comprehensive Cancer Network (NCCN), and NSGC genetic testing guidelines for women affected with ovarian, tubal, peritoneal cancers, or DNA mismatch repair deficient endometrial cancer. Three main areas of unmet need were identified: timely and universal genetic testing for women with ovarian, fallopian tube, and peritoneal cancers; education regarding minimum standards for genetic counseling and testing; and barriers to implementation of testing of both affected individuals as well as cascade testing of family members. Consensus building among all stakeholders resulted in an action plan to address gaps in education of gynecologic oncology providers and delivery of cancer genetics care.

A novel approach in pediatric telegenetic services: geneticist, pediatrician and genetic counselor team.

PurposeOur aim was to improve access to genetic services in an underserved region by developing a collaborative telegenetic service delivery model with a pediatrician, medical geneticist, and genetics counselor (GC).MethodsProtocols for the evaluation of common genetic indications were developed. Patients referred with indications suggestive of a syndromic etiology were scheduled to see the geneticist directly via telegenetics. Other patients were scheduled to see the pediatrician and GC in person before follow-up with the geneticist if indicated. Patients seen by the geneticist and/or pediatrician/GC were enumerated and the next available appointment was tracked. Patient satisfaction surveys were conducted.ResultsOf the 265 patients evaluated during the study period, 116 (44%) were evaluated by a pediatrician and GC in person first, after which 82 (71% of those evaluated) required further follow-up with the geneticist. The next available appointment with a pediatrician and GC never exceeded 6 weeks, while new appointments with a geneticist ranged from 3 to 9 months. All patients reported high satisfaction with this genetic service model.ConclusionThe pediatrician/GC clinic provides a model of collaborative care that is a medical home neighbor and exemplifies the integration of genetics into primary care. The telegenetics clinic offers a viable solution to providing competent and convenient access to a geneticist for patients in chronically underserved regions.

Complementarity between medical geneticists and genetic counsellors: its added value in genetic services in Europe.

Clinical genetic services have progressed significantly the last few decades. This has led to the need for non-medical health-care professionals working as genetic counsellors in Europe and worldwide. However, there is no unified approach to genetic counsellors' role in health-care services in Europe, as in most countries the profession is still emerging and the educational backgrounds diverge noticeably, within and between countries. This qualitative study aims to describe the potential added value of genetic counsellors in clinical genetics teams and to explore their tasks and responsibilities in different European countries. A total of 143 participants providing genetic counselling in Europe at the time of the survey responded. The results show differences in activities of genetic counsellors, although there is a wide range of roles, which are similar. The ability to establish a quality relationship with consultands was frequently mentioned as one of the strengths of genetic counsellors, as well as a patient-centred approach. It is believed that genetic counsellors add a more holistic approach of psychosocial and familial dimensions of genetic concerns to the multidisciplinary teams. This study provides examples of successful integration of genetic counsellors in teams, as complementariness with medical geneticist became clear in several cases. Although the added value of genetic counsellors was manifested, professional recognition of genetic counsellors across Europe is still needed in order to support the quality of patients care and safety of practice.

Increasing prevalence of thalassemia in America: Implications for primary care.

Thalassemia, once a rarity in the United States, is increasingly encountered in clinical practice due to shifts in immigration. Early carrier screening in at-risk populations can help clinicians implement genetic counseling and prevent new cases. Chronic transfusions are the mainstay of therapy for patients with severe thalassemia (beta thalassemia major), and are used intermittently in individuals with milder forms of thalassemia (Hb H/H Constant Spring disease and beta thalassemia intermedia). Iron overload is a major source of morbidity and mortality in individuals with transfusion and non-transfusion-dependent thalassemia, necessitating iron chelation therapy. Iron overload contributes to increased risk of cirrhosis, heart failure, and endocrinopathies, while ineffective erythropoiesis and hemolysis contribute to multiple complications, including splenomegaly, extramedullary hematopoiesis, pulmonary hypertension, and thrombosis. An understanding of the importance of carrier screening, complications, monitoring, and management strategies, coupled with collaboration with a hematologist with thalassemia expertise, is essential to reduce the morbidity and mortality in patients with thalassemia.

An investigation of genetic counselors' testing recommendations: pedigree analysis and the use of multiplex breast cancer panel testing.

Genetic testing recommendations for hereditary breast and ovarian cancer involve pedigree analysis and consultation of testing guidelines. The testing landscape for hereditary cancer syndromes is shifting as multiplex panel tests become more widely integrated into clinical practice. The purpose of the current study was to assess how genetic counselors utilize pedigrees to make recommendations for genetic testing, to determine consistency of these recommendations with National Comprehensive Cancer Network (NCCN) Guidelines and to explore current use of multiplex panel testing. Sixty-nine genetic counselors were recruited through the National Society of Genetic Counselors Cancer Special Interest Group's Discussion Forum. Participation involved pedigree analysis and completion of an online questionnaire assessing testing recommendations and use of multiplex panel testing. Pedigree analysis and test recommendations were scored for consistency with NCCN guidelines. The average score was 12.83/15 indicating strong consistency with NCCN guidelines. Participants were more likely to consider multiplex testing when pedigrees demonstrated highly penetrant dominant inheritance but were not indicative of a particular syndrome. Participant concerns about multiplex panel testing include limited guidelines for both testing eligibility and medical management. This study demonstrates high utilization of pedigree analysis and raises new questions about its use in multiplex genetic testing.

Development of an integrated support system for hereditary cancer and its impact on gynecologic services.

OBJECTIVE: Patients with hereditary cancer need an integrated support system. A recently launched project was evaluated in terms of its efficacy in screening patients with hereditary cancer at the gynecologic service. METHODS: The project team comprised gynecologists, surgeons, medical geneticists, and certified genetic counselors (CGCs) in our hospital. At the gynecologic service, a newly developed self-administered family history questionnaire (SAFHQ) was given to patients with ovarian, endometrial, or breast cancer as well as a history of multiple cancers. After an interview, a CGC constructed a pedigree and evaluated the risk for hereditary cancer. Patients at risk were recommended by a gynecologist to receive further genetic counseling at the Department of Genetics according to the modified Bethesda criteria, Amsterdam II criteria, and National Comprehensive Cancer Network (NCCN) guidelines 2012 for breast-ovarian cancer syndrome (HBOC). The numbers of newly screened patients were compared before and after the project launch. RESULTS: The SAFHQ was administered to 131 patients and 106 (81 %) pedigrees were constructed between August 2012 and July 2013. The number of newly screened patients according to the Bethesda criteria was 4 and 8 at 10 years before and 1 year after the project launch, respectively. Two and 31 patients met the NCCN criteria for HBOC excluding ovarian cancer alone, respectively, at these 2 time points. Of 54 patients who were recommended to undergo further counseling, 10 (19 %) visited the Department of Genetics. CONCLUSION: After the launch of an integrated support system, the number of patients with hereditary cancers who were screened increased. The gynecologic service played a pivotal role in patient and family care.

Longitudinal cystic fibrosis care.

Cystic fibrosis is a complex disease entity that presents considerable lifelong challenges. Implementation of medical and surgical treatment options involves multisystem interventions to prevent and treat lung and gastrointestinal manifestations of cystic fibrosis and associated comorbidities. From birth through adulthood, cystic fibrosis care entails a longitudinal regimen aimed at achieving relief of disease symptoms and enhanced life expectancy. With increased knowledge of the molecular behavior of the cystic fibrosis transmembrane conductance regulator (CFTR) in health and disease, clinical practice has been enriched by the prospect of novel strategies, including mutation-specific drug and gene therapy targeting restoration of corrupted transepithelial ion transport. Emerging paradigms of comprehensive care increasingly enable personalized solutions to address the root cause of disease-transforming management options for individuals with cystic fibrosis.

Educational priorities and current involvement in genetic practice: a survey of midwives in the Netherlands, UK and Sweden.

OBJECTIVE: to investigate whether practising midwives are adequately prepared to integrate genetic information into their practice. DESIGN: a cross-sectional, postal, structured questionnaire survey was sent to practising midwives. SETTING: practising midwives from the Netherlands (NL), Sweden (SE) and the United Kingdom (UK). PARTICIPANTS: 1021 replies were received, achieving a response rate of 62%. FINDINGS: 79% (799/1015) of midwives reported attending courses with some 'genetic content' during their initial training. Sixty-eight per cent (533/784) judged this to have been useful for clinical practice. Variation was seen between countries in the amount of genetic content in post-registration training (SE 87%, NL 44%, UK 17%) and most was considered useful. Questions assessing clinical activity identified a current need for genetic knowledge. Midwives described low levels of self-reported confidence both in overtly genetic procedures and in everyday tasks that were underpinned by genetic knowledge. For eight of the 12 procedures, fewer than 20% of midwives considered themselves to be confident. Differences were apparent between countries. Midwives identified psychosocial, screening and risk assessment aspects of genetic education as being important to them, rather than technical aspects or genetic science. CONCLUSIONS: given the low reported confidence with genetic issues in clinical practice, it is essential that this is addressed in terms of the amount, content and targeting of genetic education. This is especially important to ensure the success of national antenatal and baby screening programmes. The results of this study suggest that midwives would welcome further training in genetics, addressing genetic topics most relevant to their clinical practice.

Complementary and alternative medicine (CAM) in genetics.

Complementary and alternative medicine (CAM) is increasingly popular among families. Approximately 50% of children are on herbal preparations, 30% of adolescents take herbal medications, and 70% of adults are involved in some aspect of complementary medicine. The true incidence of CAM use by families who have a family member with special needs or a genetic condition is unknown. Anecdotal evidence suggests that usage may be higher in this group than in the general population. Geneticists and genetic counselors need to be aware of CAM practices with their families and to provide anticipatory guidance.

Ocular Genetics Program: multidisciplinary care of patients with ocular genetic eye disease.

BACKGROUND: Patients who suffer from ocular genetic diseases have special needs in terms of diagnosis and management of rare entities, low-vision needs, genetic counselling, and psychosocial adjustments that are usually not addressed by an ophthalmologist alone. The Ocular Genetics Program (OGP) at the Hospital for Sick Children, Toronto, was established in 1994 to provide comprehensive, multidisciplinary care of patients with inherited eye disorders. We now assess the benefits of such a program and of integrating research into the care of patients. METHODS: We report our experience in developing a multidisciplinary ocular genetics program and the results of a pilot patient satisfaction survey that involved 61 patients. RESULTS: The OGP multidisciplinary aspects are described. Of the 61 patients surveyed, 98% stated that they were satisfied with the OGP; 93%-96% of patients were content with "one day of appointments", "understanding of eye problem", and "coordination of ancillary tests such as visual fields test, electrophysiology, and others"; and for 70%-86% of respondents "waiting time to get an appointment", "information received on current research", and "primary health care provider adequately informed" were satisfactory. INTERPRETATION: The OGP is a unique service in Canada, which strives to provide the comprehensive care needed by ocular genetic patients. High patient satisfaction is an indicator of the success of this approach. Long waiting times for appointments and application of laboratory research in clinical care remain challenging.

Delivery of cancer genetics services: The Royal Marsden telephone clinic model.

We have conducted a telelink telephone-led cancer genetic counselling model at The Royal Marsden NHS Foundation Trust. The study commenced in March 2004 and evaluation of the clinic was conducted over 17 months from March 2005 to the end of July 2006. A total of 612 patients had telephone consultations during this time, 228 of whom were referred from primary care with a median of 30 patients counselled per month (range of 19-63, depending on staff availability with average of two staff per clinic). Waiting times were measured for General Practitioner referrals and all 228 were counselled within the national target-stipulated 13 weeks (median 6 weeks, range 1-12). An additional 132 patients who were sent appointment letters after receipt of their family history questionnaires did not attend their appointments (18% of all potential referrals) and required recontacting by letter. After telephone counselling, 42% of patients were able to be discharged from the telephone clinic without a subsequent face-to-face appointment, thereby saving resources. The telephone clinic also had a short set-up time with flexibility on timing and day of administration, which would be an advantage in centres where outreach clinic facilities are scarce. The telelink telephone counselling model is highly efficient in triaging high risk individuals for face-to-face counselling as per the Kenilworth model, in effecting concentration of resources and in providing a flexible individual-centred approach to cancer genetic counselling delivery.

Spiritual coping, family history, and perceived risk for breast cancer--can we make sense of it?

Differences in spiritual beliefs and practices could influence perceptions of the role of genetic risk factors on personal cancer risk. We explored spiritual coping and breast cancer risk perceptions among women with and without a reported family history of breast cancer. Analyses were conducted on data from 899 women in primary care clinics who did not have breast cancer. Structural equation modeling (SEM), linear, and logistic modeling tested an interaction of family history of breast cancer on the relationship between spiritual coping and risk perceptions. Overall analyses demonstrated an inverse relationship between spiritual coping and breast cancer risk perceptions and a modifying effect of family history. More frequent spiritual coping was associated with lower risk perceptions for women with positive family histories, but not for those with negative family histories. Results support further research in this area that could influence communication of risk information to cancer genetic counseling patients.