Clinical and Counseling Experiences of Early Adopters of Whole Exome Sequencing

Currently, there are limited data regarding the practice of genetic counseling for whole exome sequencing (WES). Improved understanding of how genetic counselors and other providers are educating, counseling, and communicating results may identify practice trends, and patient or provider needs. Between April 2013 and December 2014, we surveyed providers who ordered WES testing from GeneDx, a CLIA-certified laboratory. Forty-nine respondents completed the survey; 41 % of participants reported board certification in genetic counseling. Pre-test and post-test counseling was completed in all but one case each. Pre-test counseling lasted less than 1 h for 53 % of cases and 1 to 2 h for 43 %. Topics discussed with all patients included consent for testing, and incidental findings; other topics were variable. In contrast to pre-test counseling, 59 % reported post-test counseling lasting 1 to 2 h and 33 % less than an hour; post-testing counseling was significantly longer in cases with a definitive diagnosis than those without (p?=?0.0129). The survey findings indicate some variability regarding the amount of time spent on counseling and the topics discussed during pre-test counseling. Additional exploration, patient and provider educational resources, and potentially more specific guidelines regarding counseling for WES may be warranted.     

Attitude of Medical School Students in China Towards Genetic Testing and Counseling Issues in FXS

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. However, genetic testing protocols and genetic counseling guidelines for FXS are not yet established in mainland China. In the present study, we conducted a comprehensive analysis using a self-administered questionnaire among students at the Xiangya medical school to investigate their attitude towards genetic testing and counseling issues of FXS. We have gained a general understanding of the attitudes of medical students towards these FXS issues in China. This information is of immense importance to develop appropriate genetic tests and to train counselors for FXS. As the medical school students surveyed are prospective physicians who will be a part of the Chinese health system, our survey was focused on the basic knowledge of FXS, population-based FXS screening, confidentiality and reproductive options for mutation carriers. The study demonstrated that only less than one third of the participants had heard about FXS. 94.6 % of participants were in favor of FXS screening for women in their reproductive age who had a genetic history of FXS. Furthermore, only half of the participants would inform their families about their genetic status in case of positive test results, and more than half of the participants supported natural conception and prenatal diagnosis for FXS mutation carriers. Additional findings and research implications are also discussed. This survey targeting potential doctors provides important information for the development of FXS genetic test and counselor training for the Chinese health system.     

“Grasping the Grey”: Patient Understanding and Interpretation of an Intermediate Allele Predictive Test Result for Huntington Disease

Since the discovery of the genetic mutation underlying Huntington disease (HD) and the development of predictive testing, the genetics of HD has generally been described as straightforward; an individual receives either mutation-positive or negative predictive test results. However, in actuality, the genetics of HD is complex and a small proportion of individuals receive an unusual predictive test result called an intermediate allele (IA). Unlike mutation-positive or negative results, IAs confer uncertain clinical implications. While individuals with an IA will usually not develop HD, there remains an unknown risk for their children and future generations to develop the disorder. The purpose of this study was to explore how individuals understood and interpreted their IA result. Interviews were conducted with 29 individuals who received an IA result and 8 medical genetics service providers. Interviews were analyzed using the constant comparative method and the coding procedures of grounded theory. Many participants had difficulty “Grasping the Grey” (i.e. understanding and interpreting their IA results) and their family experience, beliefs, expectations, and genetic counseling influenced the degree of this struggle. The theoretical model developed informs clinical practice regarding IAs, ensuring that this unique subset of patients received appropriate education, support, and counseling.     

Impact of Panel Gene Testing for Hereditary Breast and Ovarian Cancer on Patients

Recent advances in next generation sequencing have enabled panel gene testing, or simultaneous testing for mutations in multiple genes for a clinical condition. With more extensive and widespread genetic testing, there will be increased detection of genes with moderate penetrance without established clinical guidelines and of variants of uncertain significance (VUS), or genetic variants unknown to either be disease-causing or benign. This study surveyed 232 patients who underwent genetic counseling for hereditary breast and ovarian cancer to examine the impact of panel gene testing on psychological outcomes, patient understanding, and utilization of genetic information. The survey used standardized instruments including the Impact of Event Scale (IES), Multidimensional Impact of Cancer Risk Assessment (MICRA), Satisfaction with Decision Instrument (SWD), Ambiguity Tolerance Scale (AT-20), genetics knowledge, and utilization of genetic test results. Study results suggested that unaffected individuals with a family history of breast or ovarian cancer who received positive results were most significantly impacted by intrusive thoughts, avoidance, and distress. However, scores were also modestly elevated among unaffected patients with a family history of breast and ovarian cancer who received VUS, highlighting the impact of ambiguous results that are frequent among patients undergoing genetic testing with large panels of genes. Potential risk factors for increased genetic testing-specific distress in this study included younger age, black or African American race, Hispanic origin, lower education level, and lower genetic knowledge and highlight the need for developing strategies to provide effective counseling and education to these communities, particularly when genetic testing utilizes gene panels that more commonly return VUS. More detailed pre-test education and counseling may help patients appreciate the probability of various types of test results and how results would be used clinically, and allow them to make more informed decisions about the type of genetic testing to select.     

The Evolution of Cancer Risk Assessment in the Era of Next Generation Sequencing

Cancer genetics professionals face a new opportunity and challenge in adapting to the availability of cancer genetic testing panels, now available as a result of Next Generation Sequencing (NGS) technology. While cancer panels have been available for over a year, we believe that there is not yet enough data to create practice guidelines. Despite this, a year of experience allows us to provide our opinion on points to consider as cancer genetic counselors incorporate this testing technology into genetic counseling practice models. NGS technology offers the ability to potentially diagnose hereditary cancer syndromes more efficiently by testing many genes at once for a fraction of what it would cost to test each gene individually. However, there are limitations and additional risks to consider with these tests. Obtaining informed consent for concurrent testing of multiple genes requires that genetics professionals modify their discussions with patients regarding the potential cancer risks and the associated implications to medical management. We propose dividing the genes on each panel into categories that vary by degree of cancer risk (e.g. penetrance of the syndrome) and availability of management guidelines, with the aim to improve patient understanding of the range of information that can come from this testing. The increased risk for identifying variants of uncertain significance (VUS) when testing many genes at once must be discussed with patients. Pretest genetic counseling must also include the possibility to receive unexpected results as well as the potential to receive a result in the absence of related medical management guidelines. It is also important to consider whether a single gene test remains the best testing option for some patients. As panels expand, it is important that documentation reflects exactly which genes have been analyzed for each patient. While this technology holds the promise of more efficient diagnosis for many of our patients, it also comes with new challenges that we must recognize and address.     

Factors Influencing Perceptions of Breast Cancer Genetic Counseling among Women in an Urban Health Care System

The study assessed perceptions of breast cancer genetic counseling. Focus groups were conducted with twenty women (ages < = 50 years) in a Midwestern, urban health system identified as at above average risk of developing hereditary breast cancer and referred for breast cancer genetic counseling following mammography. All participants associated the words “breast cancer” with fear. African American women who received breast cancer genetic counseling may have channeled their fear into increased vigilance related to breast health. African American women who did not receive breast cancer genetic counseling were most knowledgeable about it. In contrast, Caucasian women who did not receive it reported uncertainty about the role of genetic counseling and testing in assessing breast cancer risk, mistrust in medical professionals, and lack of trust in the accuracy of genetic tests. The results could be used to help develop interventions to improve informed decision-making regarding breast cancer genetic counseling.     

Focusing on Patient Needs and Preferences May Improve Genetic Counseling for Colorectal Cancer

During cancer genetic counseling, different items which counselors consider important are discussed. However, relatively little empirical evidence exists regarding the needs and preferences of counselees. In this study needs and preferences were assessed from counselees with a personal and/or family history of colorectal cancer (CRC), who were referred for genetic counseling regarding CRC. They received a slightly modified version of the QUOTE-GENE^ca questionnaire prior to their first visit to the Hereditary Cancer Clinic. Response rate was 60 % (48/80 participants). Counselees rated the importance of 45 items assessing their needs and preferences regarding the content and process of genetic counseling. Participants rated the items regarding discussion of information about their familial CRC risk (100 %) and preventive options (98 %) as important or very important. Fewer participants rated items concerning general information on genetics as important. Sensitive communication during counseling was considered very important by a large percentage of counselees. Generally, no major differences were seen between participants in relation to individual characteristics. Our data suggest that focusing on familial CRC risk and surveillance options, in combination with sensitive communication may lead to better satisfaction with genetic counseling.     

Genetic Risk Assessment for Women with Epithelial Ovarian Cancer: Referral Patterns and Outcomes in a University Gynecologic Oncology Clinic

Little is known about genetic service utilization and ovarian cancer. We identified the frequency and outcome of genetic counseling referral, predictors of referral, and referral uptake for ovarian cancer patients. Using pathology reports, we identified all epithelial ovarian cancer patients seen in a university gynecologic oncology clinic (1/04–8/06). Electronic medical records (EMR) were used to document genetic service referral, time from diagnosis-to-referral, point-in-treatment at referral, personal/family cancer history, demographics, and genetic test results. Groups were compared using chi-squared and Fisher’s exact test for categorical variables and t-tests for continuous variables. The study population consisted of 376 women with ovarian cancer, 72 (19 %) of who were referred for genetic counseling/testing, primarily during surveillance. Of those referred, 42 (58 %) had personal or family genetic counseling and 34 (47 %) were ultimately tested or identified due to known family mutation. Family history and prior cancer were associated with referral. Family history, living in a larger community, higher-stage disease, and serous histology were associated with undergoing genetic counseling. Risk assessment identified 20 BRCA1/2 (5.3 %) and 1 HNPCC (0.3 %) mutation carriers. Based on recent estimates that 11.7–16.6 % of women with ovarian cancer are BRCA carriers and 2 % are HNPCC carriers, results suggest under-identification of carriers and under-utilization of genetic services by providers and patients. Interventions to increase medical providers’ referrals, even in a specialized oncology clinic, are necessary and may include innovations in educating these providers using web-based methods. Ease of referral by the introduction of an electronic cancer genetic referral form represents another new direction that may increase genetic risk assessment for high-risk women with ovarian cancer.     

Telephoned BRCA1/2 Genetic Test Results: Prevalence, Practice, and Patient Satisfaction

While the traditional model of genetic evaluation for breast cancer risk recommended face-to-face disclosure of genetic testing results, BRCA1/2 testing results are increasingly provided by telephone. The few existing studies on telephone genetic counseling provide conflicting results about its desirability and efficacy. The current study aimed to (1) Estimate the prevalence among genetic counselors of providing BRCA1/2 genetic test results by phone (2) Assess patient satisfaction with results delivered by telephone versus in-person. A survey was sent to members of the Familial Cancer Risk Counseling Special Interest Group via the NSGC listserve and was completed by 107 individuals. Additionally, 137 patients who had received BRCA genetic testing results either by phone or in-person at UNC Chapel Hill Cancer Genetics Clinic were surveyed regarding satisfaction with the mode of their BRCA1/2 results delivery. The genetic counseling survey revealed that the majority of responding counselors (92.5%) had delivered BRCA1/2 genetic test results by telephone. Patients having received results either in person or by phone reported no difference in satisfaction. Most patients chose to receive results by phone and those given a choice of delivery mode reported significantly higher satisfaction than those who did not have a choice. Those who waited less time to receive results once they knew they were ready also reported higher satisfaction. This study found supportive results for the routine provision of BRCA1/2 genetic test results by telephone. Results suggest that test results should be delivered as swiftly as possible once available and that offering patients a choice of how to receive results is desirable. These are especially important issues as genetic testing becomes more commonplace in medicine.     

An Exploration of Genetic Counselors’ Needs and Experiences with Prenatal Chromosomal Microarray Testing

Because of the higher yield over traditional chromosomal analysis, chromosomal microarray analysis (CMA) is being used increasingly in prenatal diagnosis. Unfortunately, the clinical implication of many copy number variants found on prenatal CMA is uncertain, complicating genetic counseling. Recognizing that uncertain results will be encountered frequently as more of the genome is assayed prenatally, we set out to understand the experiences and needs of genetic counselors when counseling patients about uncertain prenatal microarray results, their comfort with various aspects of prenatal genetic counseling, and their interest in additional education and training about prenatal microarray testing. We first interviewed 10 genetic counselors about their experiences of providing pre- and post-test genetic counseling about prenatal CMA. Based on the findings from the counselor interviews, we developed items for a survey to assess the prevalence of genetic counselors’ attitudes towards, experience and comfort with, and educational needs regarding prenatal CMA. Based on surveys completed by 193 prenatal genetic counselors, we found that when there is an uncertain CMA result, only 59 % would be comfortable providing genetic counseling and only 43 % would be comfortable helping a patient make a decision about pregnancy termination. Being less comfortable was associated with seeing fewer patients having prenatal CMA testing. Respondents expressed a high degree of interest in additional education about prenatal CMA and counseling about uncertain results. Further genetic counselor education and training aimed at improving counselors’ personal comfort with uncertain results and communicating about them with patients is needed.     

Reproductive Endocrinologists’ Utilization of Genetic Counselors for Oncofertility and Preimplantation Genetic Diagnosis (PGD) Treatment of <Emphasis Type="Italic">BRCA1/2</Emphasis> Mutation Carriers

Genetic counselors believe fertility preservation and preimplantation genetic diagnosis (PGD) discussions to be a part of their role when counseling BRCA1/2 mutation-positive patients. This study is the first to explore reproductive endocrinologists’ (REI) practices and attitudes regarding involvement of genetic counselors in the care of BRCA1/2 mutation carriers seeking fertility preservation and PGD. A survey was mailed to 1000 REIs from Reproductive Endocrinology & Infertility (SREI), an American Society for Reproductive Medicine (ASRM) affiliate group. A 14.5 % response rate was achieved; data was analyzed using SPSS software. The majority of participating REIs were found to recommend genetic counseling to cancer patients considering fertility preservation (82 %) and consult with a genetic counselor regarding PGD for hereditary cancer syndromes (92 %). Additionally, REIs consult genetic counselors regarding PGD patient counseling (88 %), genetic testing (78 %), and general genetics questions (66 %). Two areas genetic counselors may further aid REIs are: elicitation of family history, which is useful to determine fertility preservation and PGD intervention timing (32 % of REIs utilize a cancer family history to determine intervention timing); and, interpretation of variants of uncertain significance (VOUS) as cancer panel genetic testing becomes more common (36 % of REIs are unfamiliar with VOUS). Given our findings, the Oncofertility Consortium® created an online resource for genetic counselors focused on fertility preservation education and communication strategies.     

Awareness and Preferences Regarding <Emphasis Type="Italic">BRCA1/2</Emphasis> Genetic Counseling and Testing Among Latinas and Non-Latina White Women at Increased Risk for Hereditary Breast and Ovarian Cancer

This study was an investigation of awareness, cognitions, and psychosocial and educational needs related to genetic counseling and testing among Latinas and non-Latina whites at increased risk for having a BRCA1/2 mutation. Sixty-three Latina and eighty-four non-Latina white women completed telephone surveys employing a mixture of quantitative and qualitative questions assessing awareness, benefits, risks, barriers, and genetic counseling communication preferences regarding BRCA1/2 testing. Among participants who had not previously had genetic counseling/testing, 56.9% of Latinas (29/51) and 34.8% of non-Latina white participants (24/69) were unaware of the availability of BRCA1/2 testing. In multivariate logistic regression analysis, Latina ethnicity was the only statistically significant independent factor associated with lack of awareness (OR = 0.42; 95% CI = 0.19–0.35). No appreciable differences were noted between ethnic groups regarding perceived benefits of BRCA1/2 testing or desired genetic counseling topics. These findings underscore the importance of increasing awareness of cancer genetic counseling and genetic testing among both Latina and non-Latina white populations.     

Evaluation of Group Genetic Counseling for Hereditary Breast and Ovarian Cancer

As demand for genetic counseling regarding hereditary cancer continues to grow, more efficient methods of providing this service must be explored. In this pilot study, group genetic counseling was offered to two different cohorts of women seeking genetic counseling for Hereditary Breast and Ovarian Cancer. Seven group sessions, designed to cover all aspects of an individual genetic counseling appointment, were conducted. Although patients were receptive to group genetic counseling, a significant proportion chose individual counseling when given the option. Advantages of group genetic counseling include shared experience and increased efficiency. Disadvantages include increased frustration at not being eligible for genetic testing, group influence on decision-making, privacy concerns, increased need for follow-up, and difficulty booking group appointments. Overall, the level of patient satisfaction with group genetic counseling was similar to that of individual counseling. The results of this pilot study suggest that further research is needed to determine whether group genetic counseling is an acceptable alternative to individual counseling.     

At the Heart of the Pregnancy: What Prenatal and Cardiovascular Genetic Counselors Need to Know about Maternal Heart Disease

In the last decade, an increasing number of cardiac conditions have been shown to have a genetic basis. Cardiovascular genetic counseling has emerged as a subspecialty aiming to identify unaffected at-risk individuals. An important sector of this at-risk population also includes expectant mothers, in whom unique clinical challenges may arise. Genetic counselors, especially those in cardiovascular and prenatal settings, have an opportunity to identify and assist women who may benefit from cardiovascular care during pregnancy. This paper provides basic management and genetic evaluation principles for affected women, as well as guidance on identifying those who are at risk. We provide considerations for cardiac surveillance in pregnancy and the post-partum period. Finally, key psychosocial issues that appraise how to best provide support to at risk women as they make informed decisions are discussed. We propose that a team approach including cardiology, maternal fetal medicine, and genetic counseling best serves this patient population. Ongoing questions addressing an evidence based approach to cardiovascular genetic conditions in pregnancy still remain. Thus, well-designed research protocols are essential to mark progress in this area.     

Patient Satisfaction with Cancer Genetic Counseling: A Psychometric Analysis of the Genetic Counseling Satisfaction Scale

Satisfaction is an important patient reported outcome of genetic counseling, as it is one of the elements used by professional organizations and healthcare accrediting bodies to determine the quality of professional work. However, empirical research on patient satisfaction with genetic counseling has been limited, partly due to the lack of standardized measures available to assess this construct. The purpose of this study was to conduct a psychometric analysis of a new satisfaction measure, the Genetic Counseling Satisfaction Scale (GCSS), within a sample of women participating in a no-cost cancer genetic counseling and testing program. The sample consisted of 61 women undergoing counseling and testing for hereditary breast-ovarian cancer risk (BRCA1/2 testing) who completed the GCSS following pretest counseling. The results suggest that the GCSS was reliable (Cronbach's coefficient alpha = 0.90) and that participants were highly satisfied with the care they received. In addition, there were no differences in satisfaction between cancer genetic counseling and prenatal counseling participants (based on preexisting norms), and satisfaction did not vary by sociodemographic characteristics. Implications and recommendations are discussed.     

Patient Motivation, Satisfaction, and Coping in Genetic Counseling and Testing for BRCA1 and BRCA2

Women with a strong family history of breast and/or ovarian cancer can now have genetic testing, that may identify mutations associated with increased cancer predisposition. Within the context of a clinical trial evaluating printed educational materials, we examined motivation, satisfaction, coping, and perceptions of genetic counseling and testing among 159 women who underwent pretest counseling and made a testing decision. Ninety-six percent of the participants elected to have BRCA1/2 testing. When making a decision about genetic testing, study participants were concerned less about the potential negative effects that could result from testing than the potential benefits. After counseling, participants said that they felt better able to make decisions that were right for them and that their questions and concerns were adequately addressed during the session. Ninety-five percent of the women were satisfied with their test decision. Participants used a range of strategies to cope with thoughts and feelings about cancer and/or genetic testing immediately following test decision. Results suggest that the genetic counseling session helped women make decisions about testing for BRCA1 and BRCA2, even in the setting of a trial in which all women also received detailed educational materials. Further, the results indicate that future research focusing on perceptions of risks and benefits of testing and of coping strategies immediately following test decision may be warranted.     

Attitudes Towards Prenatal Genetic Counseling,Prenatal Genetic Testing,and Termination of Pregnancy among Southeast and East Asian Women in the United States

Recognizing the heterogeneity of the Asian population with regards to acculturation, education, health awareness, and cultural values is vital for tailoring culturally sensitive and appropriate care. Prior studies show that cultural values influence perceptions of genetics within Asian populations. The reputation of the family unit factors into decisions such as pregnancy termination and disclosure of family medical history, and the nondirective model of American genetic counseling may conflict with the historical Asian model of paternalistic health care. Previous studies also provide conflicting evidence regarding correlations between education, acculturation, age, and awareness and perceptions of genetic testing. The aims of this study were to describe attitudes towards prenatal genetics among Southeast and East Asian women living in the United States for varying amounts of time and to explore sociocultural factors influencing those attitudes. Twenty-three Asian women who were members of Asian cultural organizations in the United States were interviewed via telephone about their attitudes towards prenatal genetic counseling, prenatal genetic testing, and termination of pregnancy. Responses were transcribed and coded for common themes using a thematic analysis approach. Four major themes emerged. In general, participants: (1) had diverse expectations for genetic counselors; (2) tended to weigh risks and benefits with regards to genetic testing decisions; (3) had mixed views on termination for lethal and non-lethal genetic conditions; and (4) identified cultural factors which influenced testing and termination such as lack of available resources, societal shame and stigma, and family pressure. These findings may allow prenatal genetic counselors to gain a richer, more nuanced understanding of their Asian patients and to offer culturally tailored prenatal genetic counseling.     

Risk-Reduction Surgery Decisions in High-Risk Women Seen for Genetic Counseling

Women at greatest risk for hereditary breast and ovarian cancer may consider prophylactic removal of breasts or ovaries as a risk-reduction measure. This report describes uptake of risk-reduction mastectomy (RRM), risk-reduction oophorectomy (RRO), and related factors in 62 high-risk women who received genetic counseling. Seven (11%) participants underwent RRM and 13 (21%) underwent RRO. Of these women, 37% did not have BRCA testing, suggesting other factors influence decisions to undergo surgery. Women who had indicated (pre-genetic counseling) their intent not to have surgery chose not to have surgery. Information received during genetic counseling that women perceived as being most important for influencing risk-reduction surgery decisions was BRCA test result (positive or negative), followed by discussion of family cancer history. Reasons for indecision about risk-reduction surgery included genetic testing results, concerns about surgery, timing in life, and early menopause. The findings enhance our understanding of information that is helpful to women considering this surgery.