Search

Introduction: Primary care providers (PCPs) and oncologists lack time and training to appropriately identify patients at increased risk for hereditary cancer using family health history (FHx) and clinical practice guideline (CPG) criteria. We built a tool, “ItRunsInMyFamily” (ItRuns) that automates FHx collection and risk assessment using CPGs. The purpose of this study was to evaluate ItRuns by measuring the level of concordance in referral patterns for genetic counseling/testing (GC/GT) between the CPGs as applied by the tool and genetic counselors (GCs), in comparison to oncologists and PCPs. The extent to which non-GCs are discordant with CPGs is a gap that health information technology, such as ItRuns, can help close to facilitate the identification of individuals at risk for hereditary cancer. Methods: We curated 18 FHx cases and surveyed GCs and non-GCs (oncologists and PCPs) to assess concordance with ItRuns CPG criteria for referring patients for GC/GT. Percent agreement was used to describe concordance, and logistic regression to compare providers and the tool’s concordance with CPG criteria. Results: GCs had the best overall concordance with the CPGs used in ItRuns at 82.2%, followed by oncologists with 66.0% and PCPs with 60.6%. GCs were significantly more likely to concur with CPGs (OR = 4.04, 95% CI = 3.35–4.89) than non-GCs. All providers had higher concordance with CPGs for FHx cases that met the criteria for genetic counseling/testing than for cases that did not. Discussion/Conclusion: The risk assessment provided by ItRuns was highly concordant with that of GC’s, particularly for at-risk individuals. The use of such technology-based tools improves efficiency and can lead to greater numbers of at-risk individuals accessing genetic counseling, testing, and mutation-based interventions to improve health.

Purpose: The Breast Cancer Genetics Referral Screening Tool (B-RST™) has been endorsed as one of several validated screening tools to identify women appropriate for cancer genetics referral. We conducted a randomized trial to determine the most effective means of follow-up for women who screened positive on B-RST™ 3.0. Methods: Women undergoing screening mammography at one of four Emory clinics were approached to complete the B-RST™. Participants who screened positive were randomized to one of three follow-up groups: self-referral (Group 1), electronic health record (EHR) clinician messaging (Group 2), or direct contact (Group 3). We compared genetic counseling appointment scheduling and completion rates by group. Results: Of 2,422 participants, 658 (27.2%) screened positive. Genetic counseling appointments were scheduled by 9.2%, 20.1% and 9.7% of Group 1, 2 and 3 participants respectively (p=0.001). Challenges to scheduling included lack of physician response to EHR messages and unsuccessful direct contact. Among those scheduled (n=78) 70.5% completed the appointment, with no difference between the three groups. Conclusion: B-RST™ can be used effectively in mammography settings to identify high-risk women for cancer genetics referral. Follow-up via EHR appears an acceptable and efficient approach, but additional strategies are needed to facilitate completion of the genetic counseling process.

New therapies for retinitis pigmentosa (RP) have led to patients desiring more information about their disease. We assessed the readability, content, and accountability of online health information for RP and its treatments.Two internet queries were performed: one pertaining to the condition RP, and another pertaining to treatments of RP. Three analyses were performed on the top search results that met eligibility criteria: (1) A readability analysis produced an average reading level; (2) A content analysis was conducted to score each source on the accuracy, completeness, clarity, and organization of the content; and (3) An accountability analysis was performed to evaluate adherence to accountability benchmarks, including authorship, attribution, disclosure, and currency.The mean reading level was 12.0 (SD = 3.2, 95% CI = 11.0-13.0) for the 8 RP webpages and 12.5 (SD = 3.1, 95% CI = 11.7-13.4) for the 10 RP treatment webpages. The mean content score for RP sites was 21.3 of 32 points (SD = 4.1, 95% CI = 19.5-23.0). The mean content score for RP treatment sites was 5.5 out of 16 points (SD = 3.7, 95% CI = 4.1-6.9). The inter-rater reliability was 0.973 (Cronbach's alpha). For RP sites, the mean accountability score was 2.6 out of 4 points (SD = 0.9, 95% CI = 1.9-3.4). For RP treatment sites, the mean accountability score was 2 out of 4 points (SD = 0.9, 95% CI = 1.4-2.6).Our data suggest that the online information available to patients regarding RP and RP treatment options exceeds the AMA-recommended sixth-grade reading level and contains gaps in content relevant to patients.

Previous surveys of adults with cancer have revealed increased levels of genetic knowledge, varying levels of worry, and high satisfaction with cancer genetic counseling. We sought to determine the impact of cancer genetic counseling on parental levels of genetic knowledge, worry about cancer, and satisfaction in the context of suspected cancer predisposition in a child. We hypothesized that parents would be satisfied with cancer genetic counseling and that cancer genetic counseling would improve baseline parental genetic knowledge and decrease levels of worry. Parents were recruited from a pediatric cancer predisposition clinic in the United States. A survey was administered to two cohorts: One cohort had received cancer genetic counseling in the past and only completed one survey (post-only, n = 26), and another cohort completed the survey before and after cancer genetic counseling (pre/post, n = 23). The survey included questions on demographics, knowledge of genetics, worry levels, and satisfaction with the cancer genetic counseling service. The post-genetic counseling survey also contained a free-text section for parents to indicate what they took away from the sessions. Parental levels of genetics knowledge increased by an average of 1.9 points (p = .01), with 65.2% of parents demonstrating an increase in genetics knowledge score. Average worry levels did not change significantly (p = .37), with 52.2% of parents indicating decreased worry, and 34.8% indicating increased worry. Overall, 91.8% of parents reported high levels of satisfaction. Our results show that cancer genetic counseling in a pediatric cancer predisposition clinic improves parental levels of genetics knowledge. Satisfaction rates suggest that parents find this service beneficial. These results demonstrate the positive impacts of cancer genetic counseling on parents of children in which a hereditary cancer syndrome is known or suspected.

This study aimed to evaluate the laboratory-related outcomes of participants who were offered genomic testing based on cancer family history risk assessment tools.Patients from clinics that serve populations with access barriers, who are screened at risk for a hereditary cancer syndrome based on adapted family history collection tools (the Breast Cancer Genetics Referral Screening Tool and PREMMOf all the participants, 87% successfully returned a saliva kit. Overall, 5% had a pathogenic/likely pathogenic cancer risk variant and 1% had a secondary finding. Almost all (14/15, 93%) participants completed recommended consultations with nongenetics providers after an average of 17 months. The recommended actions (eg, breast magnetic resonance imaging) were completed by 17 of 25 participants. Participant personal history of cancer and PREMMThis accessible model of hereditary cancer risk assessment and genetic testing yielded results that were often acted upon by patients and physicians.

Background Lower socioeconomic status is strongly associated with decreased perception of cancer risk. Fewer low socioeconomic status women than expected currently access cancer genetic services from which they may benefit. Patients and Methods We screened women presenting for a screening mammogram at a safety net academic hospital using the Breast Cancer Genetics Referral Screening Tool Version 3.0 (B-RSTTM), an online tool designed to identify individuals potentially at risk for hereditary breast and ovarian cancer. Participants screening either positive (high risk) or negative (moderate risk) were offered genetic counseling appointments. We used a brief survey to evaluate change in risk perception before and after using B-RSTTM, and after a genetic counseling appointment, if applicable. Barriers to accepting appointments were assessed when participants declined. Results Of the 126 participants, 91 (72.2%) screened negative-average risk, 13 (10.3%) screened negative-moderate risk, and 22 (17.5%) screened positive. Of those who screened positive or negative-moderate, 24 (68.6%) expressed interested in a genetic counseling appointment, of which 19 (79.2%) scheduled. Four of the 19 scheduled (21.1%) completed the appointment. We found a significant difference in the number who rated their breast cancer risk correctly on the post-test between the groups who self-rated as low, moderate, or high risk. Those who perceived themselves as high risk were the most likely to rate their risk correctly on the post-test (P Conclusion We showed that using B-RSTTM in a safety net academic hospital was effective at identifying women at increased risk for hereditary breast and ovarian cancer.

Molecular testing is increasingly being integrated into cancer management. Despite rapid advancements, little work has been done to explore strategies for communicating with patients undergoing molecular tumor testing. This study evaluated the impact of genetic counseling educational tools on improving patients’ understanding of key terms related to molecular testing. A genetic counseling intern designed a picture book to explain six words found in prior research to be difficult to understand (mutation, germline mutation, somatic mutation, biomarker, molecular testing, and targeted therapy). Participants who had previously discussed molecular testing with their oncologist were asked to define the terms. The same participants then received an explanation of each term either from the intern using the picture book in person or from a video presentation of the picture book. They were then asked to redefine each term afterward. The difference between the number of terms defined correctly pre- and post-intervention was compared between presentations. Sixty-three patients with melanoma, colon, lung, or breast cancer were recruited. After both interventions, correct understanding rates improved for all six terms, with significant improvement for germline mutation (p < 0.001), somatic mutation (p < 0.001), biomarker (p < 0.001), and molecular testing (p < 0.001). Understanding of targeted therapy improved significantly (p = 0.011) for the video presentation only. Mean change in knowledge scores did not differ between the two interventions (intern presentation 3.2 vs. video 2.9, p = 0.428). Our data suggest that genetic counseling educational tools can increase patient understanding of terms used to describe molecular testing.

JScreen is a national public health initiative based out of Emory University that provides reproductive carrier screening through an online portal and follow-up genetic counseling services. In 2014, JScreen began reporting to patients variants of uncertain significance (VUSs) in the gene that causes Tay-Sachs disease (HEXA). Genetic counseling was provided to discuss the VUS and patients were offered hexosaminidase A (HEXA) blood enzyme testing to assist with VUS reclassification. To identify patient reactions and factors influencing their follow-up testing decisions after receiving these results, we conducted a retrospective quantitative study by administering online surveys to 62 patients with HEXA VUSs. Participants who pursued enzyme testing and those who did not both experienced low levels of distress when receiving the VUS results. Perceptions of HEXA carrier status after genetic counseling, decisional conflict levels, plans to have children in the near future, time available to pursue enzyme testing, and eligibility for research were significant factors influencing decision-making to pursue or not pursue enzyme testing. Genetic counseling played an important role in helping patients understand the VUS and follow-up testing options. When discussing VUSs with patients, it would be beneficial for genetic counselors to focus on the patient's perception of the VUS, anxiety related to the uncertainty of their results, and follow-up options, when available.

BACKGROUND Identifying patients at risk of hereditary cancer based on their family health history is a highly nuanced task. Frequently, patients at risk are not referred for genetic counseling as providers lack the time and training to collect and assess their family health history. Consequently, patients at risk do not receive genetic counseling and testing that they need to determine the preventive steps they should take to mitigate their risk. OBJECTIVE This study aims to automate clinical practice guideline recommendations for hereditary cancer risk based on patient family health history. METHODS We combined chatbots, web application programming interfaces, clinical practice guidelines, and ontologies into a web service–oriented system that can automate family health history collection and assessment. We used Owlready2 and Protégé to develop a lightweight, patient-centric clinical practice guideline domain ontology using hereditary cancer criteria from the American College of Medical Genetics and Genomics and the National Cancer Comprehensive Network. RESULTS The domain ontology has 758 classes, 20 object properties, 23 datatype properties, and 42 individuals and encompasses 44 cancers, 144 genes, and 113 clinical practice guideline criteria. So far, it has been used to assess >5000 family health history cases. We created 192 test cases to ensure concordance with clinical practice guidelines. The average test case completes in 4.5 (SD 1.9) seconds, the longest in 19.6 seconds, and the shortest in 2.9 seconds. CONCLUSIONS Web service–enabled, chatbot-oriented family health history collection and ontology-driven clinical practice guideline criteria risk assessment is a simple and effective method for automating hereditary cancer risk screening.

Men who carry an FMR1 premutation are at-risk to develop a late-onset neurodegenerative disorder called fragile X-Associated Ataxia/Tremor syndrome (FXTAS). However, little is known about their health informational needs. This qualitative study is the first to describe diagnostic experiences and identify specific health information needs of male premutation carriers. In-depth qualitative interviews were conducted by phone with ten men who carry an FMR1 premutation. Interviews were analyzed using direct content analysis. Saturation was assessed through use of the Comparative Method for Themes Saturation in qualitative interviews (CoMeTS). Five themes were identified: diagnosis experience, sources of health information, desired health information, barriers to obtaining health information, and facilitators to desired health information. Participants desired information about inheritance, symptoms, expectations for disease, and actions available to slow progression. Facilitators to obtaining health information included healthcare provider knowledge, positive experiences with providers, beneficial family dynamics, participating in research, and access to experts. Barriers to obtaining health information included lack of personal knowledge, lack of healthcare provider knowledge, negative experiences with providers, and uncertainty. Addressing the educational needs of men with/at-risk for FXTAS could improve the quality of life of men who carry a fragile X premutation.

Background/Aims: National guidelines endorse using evidence-based tools to identify those at risk for hereditary breast and ovarian cancer (HBOC). This study aimed to evaluate whether women deemed not to be at increased risk of being a BRCA mutation carrier; the majority of those screened, recall, understand and accept the implications of these results for breast cancer risk. Methods: We conducted an online survey with women (n = 148) who screened negative on a brief HBOC screener. Results: While women tended to accept HBOC screener as accurate (range 9–45; mean 32, SD 5.0), less than half (43%) accurately recalled their result. Only 52% understood that they were at low risk of carrying a mutation, and just 34% correctly understood their breast cancer risk. African American women were less likely to recall (33 vs. 53% respectively, OR 0.5, p = 0.03), understand (42 vs. 63% respectively, OR 0.4, p = 0.02), and accept (mean 31 vs. 33 respectively, β –2.1, p = 0.02) the result compared to Whites. Conclusions: Our findings show that those at low risk of carrying a BRCA1/2 mutation had limited understanding of the distinction between mutation risk and breast cancer risk. Theory-based communication strategies are needed to increase the understanding of the implications of being at low risk for hereditary cancers.

This study aimed to assess women’s willingness to alter mammogram frequency based on their low risk for HBOC, and to examine if cognitive and emotional factors are associated with women’s inclination to decrease mammogram frequency. We conducted an online survey with women (N = 124) who were unlikely to have a BRCA mutation and at average population risk for breast cancer based on family history. Most women were either white (50%) or African American (38%) and were 50 years or older (74%). One-third of women (32%) were willing to decrease mammogram frequency (as consistent with the USPSTF guideline), 42% reported being unwilling and 26% were unsure. Multivariate logistic regression showed that feeling worried about breast cancer (Adjust OR = 0.33, p = 0.01), greater genetic risk knowledge (Adjust OR = 0.74, p = 0.047), and more frequent past mammogram screening (Adjust OR = 0.13, p = 0.001) were associated with being less willing to decrease screening frequency. Findings suggest that emerging genomics-informed medical guidelines may not be accepted by many patients when the recommendations go against what is considered standard practice. Further study of the interplay between emotion- and cognition-based processing of the HBOC screen result will be important for strategizing communication interventions aimed at realizing the potential of precision public health.

Lower socioeconomic status is strongly associated with decreased perception of cancer risk. Fewer low socioeconomic status women than expected currently access cancer genetic services from which they may benefit.We screened women presenting for a screening mammogram at a safety net academic hospital using the Breast Cancer Genetics Referral Screening Tool Version 3.0 (B-RSTOf the 126 participants, 91 (72.2%) screened negative-average risk, 13 (10.3%) screened negative-moderate risk, and 22 (17.5%) screened positive. Of those who screened positive or negative-moderate, 24 (68.6%) expressed interested in a genetic counseling appointment, of which 19 (79.2%) scheduled. Four of the 19 scheduled (21.1%) completed the appointment. We found a significant difference in the number who rated their breast cancer risk correctly on the post-test between the groups who self-rated as low, moderate, or high risk. Those who perceived themselves as high risk were the most likely to rate their risk correctly on the post-test (P .001).We showed that using B-RST

Hereditary breast and ovarian cancer syndrome (HBOC) is an inherited condition associated with mutations in the BRCA1 or BRCA2 (BRCA) genes. Identification of individuals with HBOC requires that primary care providers understand the genetic principles required to appropriately collect family history and refer individuals for genetic evaluation. A survey was developed and administered to primary care providers in Georgia to assess their existing knowledge of HBOC and direct targeted educational efforts. We found that Georgia providers demonstrate some knowledge of basic genetic principles but were unable to consistently identify individuals at risk for HBOC. Knowledge deficits included lack of understanding of inheritance patterns and failure to recognize the significance of ovarian cancer history. Strategies for improving identification of patients with HBOC include increasing provider knowledge and integrating HBOC risk assessment tools into practice. Identification of individuals at risk is the critical first step in the process of reducing incidence of breast and ovarian cancer associated with BRCA mutations.

Newborn screening (NBS) follow-up protocols vary significantly by state, and there is a need to better understand the infrastructure and communication flow of NBS programs. In addition, assessment of the educational needs of families and providers with regard to the implications of NBS results is required to inform the development of appropriate informational resources and training opportunities. To begin to address these issues, we administered a web-based survey to state NBS coordinators within the Southeast Regional Newborn Screening & Genetics Collaborative (SERC). Fourteen coordinators responded to the survey, including at least one from each of the 10 SERC states/territories. Over one-third of respondents had never received formal training regarding the metabolic conditions identified on NBS. Most communicated results via telephone or fax, though two centers indicated use of a web-based platform. Only two programs were involved in directly reporting results to the family. Four programs reported a long-term follow-up protocol. Deficits were noted for primary care provider (PCP) knowledge of metabolic disorders identified on NBS, and how to inform parents of abnormal results. Close to half indicated that the adequacy of the number of genetic counselors, dietitians, and medical/biochemical geneticists was minimal to insufficient. Respondents uniformly recognized the importance of providing additional educational and informational resources in multiple categories to NBS staff, PCPs, and families.

Evidence shows underutilization of cancer genetics services. To explore the reasons behind this underutilization, this study evaluated characteristics of women who were referred for genetic counseling and/or had undergone BRCA1/2 testing.An ovarian cancer risk perception study stratified 16,720 eligible women from the Henry Ford Health System into average-, elevated-, and high-risk groups based on family history. We randomly selected 3,307 subjects and interviewed 2,524 of them (76.3% response rate).Among the average-, elevated-, and high-risk groups, 2.3, 10.1, and 20.2%, respectively, reported genetic counseling referrals, and 0.8, 3.3, and 9.5%, respectively, reported having undergone BRCA testing. Personal breast cancer history, high risk, and perceived ovarian cancer risk were associated with both referral and testing. Discussion of family history with a doctor predicted counseling referral, whereas belief that family history influenced risk was the strongest BRCA testing predictor. Women perceiving their cancer risk as much higher than other women their age were twice as likely (95% confidence interval: 2.0-9.6) to report genetic counseling referral.In a health system with ready access to cancer genetic counseling and BRCA testing, women who were at high risk underutilized these services. There were strong associations between perceived ovarian cancer risk and genetic counseling referral, and between a belief that family history influenced risk and BRCA testing.

Despite increased awareness of hereditary breast and ovarian cancer among clinicians and the public, many BRCA1/2 mutation carriers remain unaware of their risk status. The Breast Cancer Genetics Referral Screening Tool (B-RST™) was created and validated to easily identify individuals at increased risk for hereditary breast and ovarian cancer for referral to cancer genetics services. The purpose of this study was to revise B-RST™ to maximize sensitivity against BRCA1/2 mutation status. We analyzed pedigrees of 277 individuals who had undergone BRCA1/2 testing to determine modifications to the B-RST™ 2.0 algorithm that would maximize sensitivity for mutations, while maintaining simplicity. We used McNemar’s chi-square test to compare validation measures between the revised version (3.0) and the 2.0 version. Algorithmic changes made to B-RST™ 2.0 increased the sensitivity against BRCA1/2 mutation analysis from 71.1 to 94.0% (P

It took Angelina Jolie’s announcement in 2013 to bring broad awareness of hereditary breast and ovarian cancer (HBOC) to the general public. However, it has been 25 years since MaryClaire King mapped BRCA1 to chromosome 17 through linkage analysis involving painstaking collection of a large number of families with multiple cases of early-onset breast cancer. Though familial “clusters” of breast cancer had been described since the early 1800s, the concept that cancer can result from inheritance of a single faulty gene first made its way into the scientific literature when Knudson published his famous “2-hit hypothesis” in 1971. Lynch et al were one of the first to describe the association of breast with ovarian cancer in a 1978 article entitled “Familial Association of Breast and Ovarian.” However, it was the pioneering work of Gardner and Stephens initiated in the mid-1940s identifying and following large Mormon kindreds in Utah that ultimately drove the search for the “breast cancer gene.” Despite the work of Knudson, Lynch, Gardner, and others, the research and clinical communities remained skeptical well into the early 1980s that breast cancer could be hereditary, as opposed to primarily the result of environmental and lifestyle factors. The race to isolate the BRCA1 gene was ultimately won by Mark Skolnick, founder of Myriad Genetic Laboratories, Inc, in 1994, followed closely by the cloning of BRCA2 in 1995. At that time, despite the evidence of increased incidence of ovarian cancer in BRCA1 and BRCA2 families, many still believed there was an ovarian cancer–only gene that was responsible for pedigrees segregating multiple ovarian cancer cases, but no breast cancer. However, further study confirmed that there was not an “OVCA1” gene, and that BRCA1 and BRCA2 accounted for most familial site-specific ovarian cancer. In addition, the failure to find a BRCA1 and BRCA2 mutation in many apparently classic HBOC families led to the search for “BRCA3.” Ultimately it was determined that there likely did not exist another single major hereditary cancer gene responsible for most BRCA1and BRCA2-negative families.

The Georgia Breast Cancer Genomic Health Consortium is a partnership created with funding from the Centers for Disease Control and Prevention (CDC) to the Georgia Department of Public Health to reduce cancer disparities among high-risk minority women. The project addresses young women at increased risk for hereditary breast and ovarian cancer (HBOC) syndrome through outreach efforts.The consortium provides education and collects surveillance data using the breast cancer genetics referral screening tool (B-RST) available at www.BreastCancerGeneScreen.org . The HBOC educational protocol was presented to 73 staff in 6 public health centers. Staff used the tool during the collection of medical history. Further family history assessments and testing for mutations in the BRCA1/2 genes were facilitated if appropriate.Data was collected from November 2012 through December 2013, including 2,159 screened women. The majority of patients identified as black/African American and were 18-49 years old. Also, 6.0 % (n = 130) had positive screens, and 60.9 % (n = 67) of the 110 patients who agreed to be contacted provided a detailed family history. A total of 47 patients (42.7 %) met National Comprehensive Cancer Network guidelines when family history was clarified. Fourteen (12.7 %) underwent genetic testing; 1 patient was positive for a BRCA2 mutation, and 1 patient was found to carry a variant of uncertain significance.The introduction of genomics practice within public health departments has provided access to comprehensive cancer care for uninsured individuals. The successful implementation of the B-RST into public health centers demonstrates the opportunity for integration of HBOC screening into primary care practices.

There is a lack of information about knowledge gaps in the lysosomal storage disease (LSD) population, which limits the capacity for proper genetic counseling. This is the first study to discern these gaps and assesses if online information can fill them. This study consists of a pre-survey, a research period, and a post-survey. The pre-survey collects demographic information, tests knowledge, and determines participants’ questions. Questions are split into current and initial questions (from the time of diagnosis). Participants are then directed to ThinkGenetic.com, a source for accurate and current genetic information, for research at their leisure. The post-survey determines if knowledge scores improved and if questions were answered. 100 participants were recruited from the Emory University Lysosomal Storage Disease Clinic. 34 participants achieved perfect scores (5) on both surveys. Scores changed for 34 participants, in which all but 4 increased. The median increase was 1. All decreased scores lowered by 1 point. The majority of initial and current questions pertained to treatment. Initial questions also focused on daily living and general knowledge of the disease. Current questions also focused on daily living. 51 participants reported finding answers to their initial questions, whereas only 33 participants reported finding answers to their current questions. Participants reported that questions remained about treatment, research studies, and daily living, indicating that this is where their knowledge gaps lie. The data suggests that accurate online information can answer questions at the time of diagnosis. However, as they live longer with the disease, participants accumulate questions that may require further research. The small increase in knowledge scores is attributed to the small number of knowledge questions and the high baseline knowledge of the cohort. We will continue this study with more LSD patients, family members, and caregivers.

An understanding of the diagnosis and clinical management of hereditary breast and ovarian cancer syndrome (HBOC) is essential for obstetricians/gynecologists. This article provides practical information regarding collecting a family history, cancer risk assessment and genetic testing, BRCA-associated cancer prognosis and treatment, screening recommendations, and prevention strategies. Through appropriate cancer risk assessment, women with BRCA1/2 mutations can be identified, and screening and prevention strategies can be used before a diagnosis of cancer occurs. Women's health providers with a strong working knowledge of HBOC are able to improve the quality of care for women and families impacted by BRCA1/2 mutations.

Background: In 2005, the United States Preventive Services Task Force (USPSTF) released guidelines which outlined specific family history patterns associated with an increased risk for BRCA1/2 mutations, and recommended at-risk individuals be referred for genetic counseling and evaluation for BRCA testing. The purpose of this study was to assess the prevalence of individuals with a USPSTF increased-risk family history pattern, the frequency with which specific patterns were met, and resulting healthcare actions among women from the Henry Ford Health System. Methods: As part of a study evaluating ovarian cancer risk perception and screening, 2,524 randomly selected participants completed a detailed interview (response rate 76%) from an initial eligible cohort of 16,720 women. Results: Approximately 6% of participants had a family history fulfilling one or more of the USPSTF patterns. Although 90% of these women had shared their family history with their provider, less than 20% had been referred for genetic counseling and only 8% had undergone genetic testing. Caucasian women with higher income and education levels were more likely to receive referrals. Among the 95 participants in the total study cohort who reported BRCA testing, 78% did not have a family history that met one of the USPSTF patterns. Conclusions: These results suggest a higher prevalence of women with an increased-risk family history than originally predicted by the USPSTF, and lack of provider recognition and referral for genetic services. Impact: Improvements in healthcare infrastructure and clinician education will be required to realize population level benefits from BRCA genetic counseling and testing. Cancer Epidemiol Biomarkers Prev; 22(4); 728–35. ©2013 AACR.

The last several years has witnessed an explosion in genomics, with the advent of genome-wide association studies revealing hundreds of DNA variants significantly associated with most common diseases, including cancer. On the heels of these scientific advances came the direct-to-consumer (DTC) genetic testing industry. Genome-wide scans for disease have been marketed and sold directly to the public, without the involvement of a health care provider. Unlike genetic testing for mutations in known hereditary cancer susceptibility genes such as BRCA1/2, these genomic profiles examine DNA variants, which typically have a minimal risk impact, and account for only a fraction of the heritable component of cancer. Furthermore, risk information provided to consumers does not account for family history or other known risk factors. The clinical validity and utility of personal genome scans for disease risk prediction remain for the most part unestablished, although some argue lack of evidence of harm and the possibility that positive impacts on health behaviors or genetic awareness may result from consumer use. The DTC genetic testing industry has sparked significant controversy not only among the scientific community, but also among professional societies and government agencies.In this review, we present some of the history and methodological considerations of DTC genomic profiling, with a focus on cancer risk prediction. The literature regarding consumer awareness and utilization is explored, including understanding, expectations, and behavioral and psychological responses to DTC genomic risk prediction. Primary care provider and genetic professional knowledge and perceptions of DTC genomic profiling are also addressed. Ethical and scientific controversy surrounding the DTC genetic testing industry is presented, along with policy recommendations, regulatory actions, and the changing landscape of the DTC genetic testing market in response. Although our understanding of the human genome holds much promise in the realm of cancer prevention and treatment, DTC genomic profiling for cancer risk prediction is unlikely in its current form to have any significant impact on the health of the public. Time will tell if the next venture in genomic medicine, whole genome sequencing, will be accompanied by the translational research and emphasis on public/provider education required to ensure its successful application toward reducing the burden of cancer at a population level.

T he genomic revolution has the potential to change the practice of medicine and healthcare. Advances in technology are driving down the cost of genetic testing, the public is more aware of and interested in such testing and its uses, and genetic testing companies are now offering direct-to-consumer (DTC) testing via kits sold on the Internet. Some argue that these changes make genetic testing more accessible to the general public and medical community at large and that these changes are critical to the full integration of genomic technology into society. However, many of the DTC tests offered are of questionable accuracy and utility and combine tests that provide mundane information about genetic traits with those for serious genetic conditions with life-threatening implications for the patient and the entire family. We will examine both sides of the issues surrounding DTC genetic testing, focusing on important considerations for clinicians using case vignettes to illustrate key issues.

1592Background: Molecular testing is increasingly being integrated into cancer management. However, despite rapid advancements in this area, little work has been done to explore strategies for comm...

1514Background: It is estimated that less than 10% of BRCA1/2 mutation carriers have been identified, despite well-documented evidence of reduced cancer morbidity and mortality with targeted screen...

Purpose: Simple screening tools are needed to facilitate the appropriate referral of patients for genetic counseling and testing for BRCA1/2 mutations. This study evaluated the reliability and accuracy of a “referral screening tool” designed for rapid identification of individuals at potential hereditary risk for breast/ovarian cancer. Methods: The referral screening tool was administered to 2464 unselected women undergoing screening mammography. Detailed four-generation cancer pedigrees were collected by telephone interview on a random subset of 296 women. The pedigrees were analyzed using four established hereditary risk models (BRCAPRO, Myriad II, BOADICEA, FHAT), with a ≥10% BRCA1/2 mutation probability or a FHAT score of ≥10 as the definition of “high risk.” Results: The referral screening tool identified 6.2% of subjects as screen “positive” (high risk). Concordance of randomly repeated referral screening tools (156 of 2464) was 96% (kappa = 0.75). In comparison with the pedigree analyses, the referral screening tool demonstrated an overall (high risk by any model) sensitivity of 81.2%, specificity of 91.9%, and discriminatory accuracy of 0.87. Conclusions: Within the population studied, the referral screening tool seems to be a reliable and valid tool to identify individuals who should be referred for consideration of BRCA1/2 testing. Further examination of the referral screening tool in primary care settings is warranted to assess its impact on the efficiency with which health care providers triage patients to cancer genetics services.

The Evaluation of Genomic Applications in Practice and Prevention Working Group published an evidence-based recommendation stating that every newly diagnosed colorectal cancer (CRC) should undergo tumor screening for Lynch syndrome (LS). In 2011, leading cancer institutions and public health agencies created the Lynch Syndrome Screening Network (LSSN) in order to promote routine LS screening on all newly diagnosed CRCs and endometrial cancers (EC). The LSSN facilitates implementation of appropriate screening via shared resources, protocols and data through network collaboration. The LSSN website contains resources for institutions interested in initiating screening, including materials for program development, implementation and sustainability. The LSSN listserv gives providers access to experts in LS screening and implementation. The LSSN database will allow exploration of key gaps in implementation as a consortia-wide endeavor. To date, the LSSN’s membership includes 85 institutions involved in the care of CRC patients and nine official partners such as national and state public health entities and other non-profit institutions. Nearly 80 % of the LSSN’s members have already implemented routine or universal CRC and/or EC screening. LSSN serves to further the population health potential of universal LS screening through collaborative efforts and resources.

Introduction Understanding the characteristics of early and late survey responders has implications for recruitment efforts and for informing potential response bias. The main objective of this analysis was to examine survey responder status (ie, early vs late response) by sociodemographic characteristics and by salience of study variables among respondents. Methods We analyzed data from a survey on family cancer history and perceived cancer risk among women at a large managed health-care organization. For baseline and 12-month follow-up surveys, we defined early versus late responder status according to the 95th percentile of the number of days it took to obtain completed interviews. Results We found no significant associations between responder status and sociodemographic characteristics at baseline or follow-up. At baseline, early responders were significantly more likely than late responders to have a personal history of breast cancer (5.2% vs 3.4%, P = .04) and to have been referred for genetic counseling (4.6% vs 2.0%, P = .004). The association between personal history of breast cancer and responder status persisted at follow-up; only 3.5% of late responders at baseline were also late responders at follow-up. Follow-up survey nonresponse rates did not vary by baseline responder status. Conclusion Survey topic salience is associated with early response and is important for recruitment. However, once recruited, late responders do not remain late responders at follow-up, suggesting that extra efforts made to recruit late responders are worthwhile. Health-related agencies that conduct surveys should consider survey salience in survey administration and recruitment strategies.

Lynch syndrome is the most common cause of inherited colorectal cancer, accounting for approximately 3% of all colorectal cancer cases in the United States. In 2009, an evidence-based review process conducted by the independent Evaluation of Genomic Applications in Practice and Prevention Working Group resulted in a recommendation to offer genetic testing for Lynch syndrome to all individuals with newly diagnosed colorectal cancer, with the intent of reducing morbidity and mortality in family members. To explore issues surrounding implementation of this recommendation, the Centers for Disease Control and Prevention convened a multidisciplinary working group meeting in September 2010. This article reviews background information regarding screening for Lynch syndrome and summarizes existing clinical paradigms, potential implementation strategies, and conclusions which emerged from the meeting. It was recognized that widespread implementation will present substantial challenges, and additional data from pilot studies will be needed. However, evidence of feasibility and population health benefits and the advantages of considering a public health approach were acknowledged. Lynch syndrome can potentially serve as a model to facilitate the development and implementation of population-level programs for evidence-based genomic medicine applications involving follow-up testing of at-risk relatives. Such endeavors will require multilevel and multidisciplinary approaches building on collaborative public health and clinical partnerships.

Differences in the expression of specific genes within breast tumors have been associated with risk of recurrence after treatment. Most women with Stage I or II node-negative breast cancer (especially when estrogen-receptor positive and treated with tamoxifen) remain disease-free at 10 years. Information on risk of recurrence could help identify women most likely to benefit from chemotherapy. Several clinically available gene expression profiles (GEP) providerecurrence risk scoresthat are intended to supplement information used by clinicians and patients in treatment decision-making. Abstract Differences in the expression of specific genes within breast tumors have been associated with risk of recurrence after treatment. Most women with Stage I or II node-negative breast cancer (especially when estrogen-receptor positive and treated with tamoxifen) remain disease-free at 10 years. Information on risk of recurrence could help identify women most likely to benefit from chemotherapy. Several clinically available gene expression profiles (GEP) providerecurrence risk scoresthat are intended to supplement information used by clinicians and patients in treatment decision-making. Abstract Differences in the expression of specific genes within breast tumors have been associated with risk of recurrence after treatment. Most women with Stage I or II node-negative breast cancer (especially when estrogen-receptor positive and treated with tamoxifen) remain disease-free at 10 years. Information on risk of recurrence could help identify women most likely to benefit from chemotherapy. Several clinically available gene expression profiles (GEP) providerecurrence risk scoresthat are intended to supplement information used by clinicians and patients in treatment decision-making.

Lynch syndrome is the most common hereditary colorectal cancer syndrome and the most common cause of hereditary endometrial cancer. Identifying and evaluating families for Lynch syndrome is increasing in complexity due to the recognition that: family history-based clinical criteria lack sensitivity and specificity; genetic testing for Lynch syndrome continues to evolve as understanding of the molecular mechanisms underlying it evolves; and the Lynch syndrome phenotype encompasses multiple organ systems and demonstrates overlap with other hereditary cancer syndromes. This document is a summary of considerations when evaluating individuals and families for Lynch syndrome, including information on cancer risks, diagnostic criteria, tumor and genetic testing strategies, and the management of individuals with this condition.

Background Testing for mutations in the breast and ovarian cancer susceptibility genes BRCA1 and BRCA2 ( BRCA ) has been commercially available since 1996. Purpose This study sought to determine, among U.S. primary care physicians, the level of awareness and utilization of BRCA testing and the 2005 U.S. Preventive Services Task Force (USPSTF) recommendations. Methods In 2009, data were analyzed on 1500 physician respondents to the 2007 DocStyles national survey (515 family practitioners, 485 internists, 250 pediatricians, and 250 obstetricians/gynecologists). Results Overall, 87% of physicians were aware of BRCA testing, and 25% reported having ordered testing for at least one patient in the past year. Ordering tests was most prevalent among obstetricians/gynecologists in practice for more than 10 years, with more affluent patients. Physicians were asked to select indications for BRCA testing from seven different clinical scenarios representing increased (4) or low-risk (3) situations consistent with the USPSTF guidelines. Among ordering physicians (pediatricians excluded), 45% chose at least one low-risk scenario as an indication for BRCA testing. Only 19% correctly selected all of the increased-risk and none of the low-risk scenarios. Conclusions A substantial majority of primary care physicians are aware of BRCA testing and many report having ordered at least one test within the past year. A minority, however, appear to consistently recognize the family history patterns identified by the USPSTF as appropriate indications for BRCA evaluation. These results suggest the need to improve providers' knowledge about existing recommendations—particularly in this era of increased BRCA direct-to-consumer marketing.

We report clinical and molecular studies on a large American family of Norwegian descent with X-linked nonprogressive congenital ataxia (XCA) in six affected males over three generations. Neuroimaging showed global cerebellar hypoplasia without evidence of supratentorial anomalies. Linkage analysis resulted in a maximum LOD score Z = 3.44 for marker DXS1192 at Theta = 0.0 with flanking markers DXS1047 and DXS1227 defining a region of 12 cM in Xq25-q27.1. The clinical and neuroradiological findings in the present family are very similar to those described in two reported X-linked families [Illarioshkin et al., 1996; Bertini et al., 2000]; however, the newly identified locus does not overlap with the one defined previously, indicating that there are at least two genes responsible for this rare form of X-linked congenital cerebellar ataxia with normal intelligence.

Further development and evaluation of a breast/ovarian cancer genetics referral screening tool