Knowledge outcomes in a randomized trial of telephone vs. in-person disclosure of genetic testing: The COGENT study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1534-1534
Author(s):  
Nina Beri ◽  
Linda J. Patrick-Miller ◽  
Brian L. Egleston ◽  
Olufunmilayo I. Olopade ◽  
Michael J. Hall ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Randomized Trial ◽  
Genetic Knowledge ◽  
True Negative ◽  
Variant Of Uncertain Significance ◽  
Knowledge Change ◽  
Negative Results ◽  
Genetic Test Results ◽  
Uncertain Significance ◽  
Multivariable Analyses

1534 Background: Telephone disclosure (TD) of genetic testing is non-inferior to in-person disclosure (IPD) for most outcomes but did not meet non-inferiority for knowledge change. We sought to understand which concepts patients don’t understand and factors associated with lower knowledge. Methods: Patients were recruited to a multi-center, randomized trial (NCT01736345) comparing TD to IPD of genetic test results. 819 patients were randomized (IPD = 418; TD = 401); 165 declined randomization and requested IPD. Knowledge was assessed after pre-test counseling (V1) and test disclosure (V2). Results: There were no significant differences in genetic or multi-gene (MG) knowledge between disclosure groups after V1 and V2. On average, patients answered 73% (SD 1.19) of genetic knowledge and 57% (SD 1.78) of mg knowledge items correctly.After V1, most understood implications of a positive result (87%), that results are not deterministic (84%) and risks for their children (91%). Understanding of uninformative negative, true negative and variant of uncertain significance (VUS) results was lower (post-V1: 33%, 65%, 29%; post-V2 : 37%, 65%, 25%). In multivariable analyses, lower genetic knowledge after V1 was associated with study site, being older (p < 0.01), single (p < 0.01), non-white (p < 0.01), not Ashkenazi Jewish (p = 0.01), and not having a mutation in the family (p = 0.03), having more relatives with cancer (p < 0.01) and not graduating college (p < 0.01). Lower mg knowledge after V1 was associated with site and being non-white (p = 0.01). Lower genetic knowledge after V2 was not associated with disclosure method but associated with study site, being older (p < 0.01), not graduating college (p < 0.01) and being non-white (p < 0.01). Lower mg knowledge after V2 was only associated with not graduating college (p = 0.02). Conclusions: While there were no significant differences in genetic knowledge by disclosure method, understanding of several concepts (e.g. VUS and negative results) were lower regardless of arm. Several factors, including age, education and race/ethnicity were associated with lower knowledge. Interventions to improve genetic knowledge in real-world and diverse populations are needed. Clinical trial information: NCT07136345.

Randomized trial of web-based genetic education versus usual care in advanced cancer patients undergoing tumor genetic testing: Results from the ECOG-ACRIN NCI Community Oncology Research Program (NCORP; EAQ152) COMET trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2008-2008
Author(s):  
Angela R. Bradbury ◽  
Ju-Whei Lee ◽  
Jill B Gaieski ◽  
Shuli Li ◽  
Ilana F Gareen ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Usual Care ◽  
Genetic Test ◽  
Genetic Knowledge ◽  
Test Results ◽  
Advanced Cancer Patients ◽  
Web Based ◽  
Genetic Test Results ◽  
Anxiety Depression ◽  
Web Intervention

2008 Background: Enthusiasm for precision oncology may obscure the complex psychosocial and ethical considerations for tumor genetic testing. Low patient genetic knowledge has been documented and heightens the risk for adverse experiences. We developed a web-based intervention to increase genetic knowledge and decrease distress among advanced cancer patients undergoing tumor genetic testing. Methods: 594 patients (80% from NCORP Community Sites) were recruited and randomized to web-intervention (n = 293) or usual care (n = 301), prior to receipt of tumor genetic test results. Primary outcomes were genetic knowledge, anxiety, depression, and cancer-specific distress measured at T0 (prior to intervention), T1 (post-intervention), T2 (after receipt of tumor results) and T3 (3 months post receipt of tumor results). Secondary outcomes included satisfaction, regret and disappointment. The effect of web-intervention was evaluated using t-test, multiple linear regression and logistic regression, with an intent-to-treat approach. Results: Patients randomized to web-intervention had better knowledge improvement than those randomized to usual care (T1-T0, p < 0.0001; T2-T0, p = 0.003). No difference was observed in change scores for anxiety, depression or cancer-specific distress. To find the moderators of intervention effect (including sex, age, education, and literacy) two 2-way interactions were noted with statistical significance: higher depression among those in the intervention arm versus the control arm for patients with lower literacy (p = 0.03); and lower cancer-specific distress among women in the intervention arm than with usual care but no such effect noted in men (p = 0.01). 71% of patients reported receiving tumor test results and this did not differ by arm. Only 20% of patients reported regret and disappointment at T2, which was more likely for those without a mutation of interest (MOI) detected vs those with a MOI detected (OR = 2.08, 95% CI, 1.13 to 3.83, p = 0.02). Conclusions: Web-based education prior to receipt of tumor genetic test results increases patient understanding of tumor genetic testing. While the intervention did not significantly reduce distress, results suggest that women who received the intervention had lower cancer-specific distress than those with usual care. Future refinements to the web-intervention are needed to address low literacy groups, men and patients with no actionable results. Clinical trial information: NCT02823652.

Exome Sequencing Highlights a Potential Role for Concealed Cardiomyopathies in Youthful Sudden Cardiac Death

2021 ◽  
Author(s):  
Raquel Neves ◽  
David J. Tester ◽  
Michael A. Simpson ◽  
Elijah R. Behr ◽  
Michael J. Ackerman ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Strong Evidence ◽  
Susceptibility Gene ◽  
Susceptibility Genes ◽  
Medical Genetics ◽  
Variant Of Uncertain Significance ◽  
Pathogenic Variants ◽  
Genetic Test Results ◽  
Uncertain Significance ◽  
Genetics And Genomics

Background: Sudden cardiac arrest (SCA) and sudden unexplained death (SUD) are feared sequelae of many genetic heart diseases. In rare circumstances, pathogenic variants in cardiomyopathy-susceptibility genes may result in electrical instability leading to SCA/SUD before any structural manifestations of underlying cardiomyopathy are evident. Methods: Collectively, 38 unexplained SCA survivors (21 males; mean age at SCA 26.4±13.1 years), 68 autopsy-inconclusive SUD cases (49 males; mean age at death 20.4±9.0 years) without disease-causative variants in the channelopathy genes, and 973 ostensibly healthy controls were included. Following exome sequencing, ultrarare (minor allele frequency ≤0.00005 in any ethnic group within Genome Aggregation Database [gnomAD, n=141 456 individuals]) nonsynonymous variants identified in 24 ClinGen adjudicated definitive/strong evidence cardiomyopathy-susceptibility genes were analyzed. Eligible variants were adjudicated as pathogenic, likely pathogenic, or variant of uncertain significance in accordance with current American College of Medical Genetics and Genomics guidelines. Results: Overall, 7 out of 38 (18.4%) SCA survivors and 14 out of 68 (20.5%) autopsy-inconclusive, channelopathic-negative SUD cases had at least one pathogenic/likely pathogenic or a variant of uncertain significance nonsynonymous variant within a strong evidence, cardiomyopathy-susceptibility gene. Following American College of Medical Genetics and Genomics criterion variant adjudication, a pathogenic or likely pathogenic variant was identified in 3 out of 38 (7.9%; P =0.05) SCA survivors and 8 out of 68 (11.8%; P =0.0002) autopsy-inconclusive SUD cases compared to 20 out of 973 (2.1%) European controls. Interestingly, the yield of pathogenic/likely pathogenic variants was significantly greater in autopsy-inconclusive SUD cases with documented interstitial fibrosis (4/11, 36%) compared with only 4 out of 57 (7%, P <0.02) SUD cases without ventricular fibrosis. Conclusion: Our data further supports the inclusion of strongevidence cardiomyopathy-susceptibility genes on the genetic testing panels used to evaluate unexplained SCA survivors and autopsy-inconclusive/negative SUD decedents. However, to avoid diagnostic miscues, the careful interpretation of genetic test results in patients without overt phenotypes is vital.

Parent perceptions of offspring responses to parental communication of BRCA1/2 test results

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1511-1511 ◽  
Author(s):  
A. R. Bradbury ◽  
L. Patrick-Miller ◽  
B. Egleston ◽  
C. Sands ◽  
M. Feigon ◽  
...  
Keyword(s):  
Genetic Test ◽  
Positive Impact ◽  
Childhood And Adolescence ◽  
Test Results ◽  
Variant Of Uncertain Significance ◽  
Mutation Carriers ◽  
Genetic Test Results ◽  
Self Reports ◽  
Uncertain Significance ◽  
The Impact

1511 Background: Many BRCA1/2 mutation carriers report sharing their genetic test results with their minor children. The impact of this communication on offspring remains unknown. Methods: 163 parents who had BRCA1/2 testing completed qualitative interviews regarding their experiences with communication of their genetic test results to offspring. Descriptive responses were coded and response proportions utilized to summarize results. We used multiple regressions fit by GEE to test associations with disclosure. We controlled for parent mutation status in each regression. Results: 163 parents (52 BRCA1/2 mutation carriers) reported on 323 offspring 5 to 25 years old at the time of parent genetic testing. 107 (66%) parents reported disclosing to at least one offspring. Child age (p < 0.001) and parent cancer history (p = 0.004) were positively associated with disclosure. Parents without a BRCA1/2 mutation were more likely to communicate test results than parents with a mutation (p = 0.007). Among parents who disclosed, few (14%) reported they perceived their offspring to have had an initial negative affective or behavioral response. Others (13%) reported offspring concern for self and family. Reports of initial negative responses and concern were more frequent among parents with a mutation or a variant of uncertain significance. Many parents reported that the communication had no significant impact (39%) or a positive impact (36%) on their offspring. Conclusions: Many parents report sharing BRCA1/2 test results with their offspring. Parent self-reports suggest that they do not perceive most offspring to experience adverse reactions to this communication. Self-reports suggest that offspring learning of a BRCA1/2 mutation or a variant of uncertain significance may be more susceptible to initial negative reactions. Further research is necessary to explore psychosocial and behavioral responses to learning of hereditary risk during childhood and adolescence, and to inform the development of interventions to optimize adaptive response. No significant financial relationships to disclose.

scholarly journals Logistics and Uptake of Genetic Testing for Patients Referred for Telegenetic Counselling for Cancer

2018 ◽  
Vol 6 ◽  
Author(s):  
Kate Parks Shane-Carson ◽  
Cortlandt Martin
Keyword(s):  
Genetic Testing ◽  
Pathogenic Mutation ◽  
Ohio State University ◽  
State University ◽  
Completion Rates ◽  
Variant Of Uncertain Significance ◽  
Counselling Session ◽  
Uncertain Significance ◽  
The Ohio State University

Purpose:  There is a dearth of information about the uptake of genetic testing after telegenetic (videoconference) counselling for hereditary cancer, which has been previously reported as a limitation of this service delivery model.  Methods:  We performed a review of the triage list for patients referred to The Ohio State University (OSU) from two community cancer centres for telegenetic counselling appointments from April 1, 2014 to May 31, 2016.  Results:  A total of 179 patients were referred for telegenetic counselling, and of   these 62.6% (112/179) completed a 30-60 minute telegenetic counselling appointment.   Of those counselled, 82.1% (92/112) completed genetic testing,    12.0% (11/92) of whom were found to have a pathogenic mutation.  Of those with mutations, 45.5% (5/11) returned for a follow-up telegenetic counselling session to review results in more detail.  In addition, 18.5% (17/92) of patients tested had at least one variant of uncertain significance (VUS). Conclusions:  The presence of a nurse/nurse practitioner with the patient at the remote site during the telegenetic counselling session may have facilitated higher completion rates for genetic testing compared to previous reports in the literature, and appropriateness of genetic testing in this method of providing genetic counselling is reflected in the rates of results identifying deleterious mutations and variants of uncertain significance.

Genetic testing referral, uptake, and results in a program for women age 40 or younger with breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1542-1542
Author(s):  
Asma Ali ◽  
Ellen Warner ◽  
Kimberley Hill
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Young Women ◽  
Epidemiological Data ◽  
The Other ◽  
Brca Testing ◽  
Variant Of Uncertain Significance ◽  
Mutation Carriers ◽  
Uncertain Significance ◽  
Testing Uptake

1542 Background: PYNK: Breast Cancer Program for Young Woman is a novel program started in 2008 at our center to optimize management and promote research for women ≤ age 40 newly diagnosed with breast cancer. Clinical and epidemiological data including cancer family history (FH) is prospectively collected on each consenting patient. As Toronto’s population is uniquely multiethnic we sought to determine BRCA testing eligibility, uptake and results for PYNK patients. Methods: Of the 145 consecutive patients, data were available for 109, of whom 2 had testing prior to diagnosis. Our provincial BRCA testing criteria are age < 35 at diagnosis; suspicious FH; or Ashkenazi Jewish (AJ) and age < 50 at diagnosis. Results: Of the 107 previously untested patients, 40 were < 35 at diagnosis. In 5 of the other 67 testing eligibility could not be assessed. 66 of the 102 (65%) were eligible and of those 65 (98%) were offered referral for counseling. One declined counseling, 9 were not yet seen, 2 declined testing, and 53 were tested. Test results are available for 47 as follows: 30 (64%) no mutation, 4 (8%) variant of uncertain significance (VUS), 7(15%) BRCA1 mutations and 6 (13%) BRCA2 mutations including 1 of the 4 AJ women. Ethnicity of the other 12 mutation carriers was: 1 Hispanic, 2 European, 2 African, 4 Asians, 1 mix, 1 unknown and 1 not recorded. Two (15%) of the mutation carriers had no FH of breast or ovarian cancer. Four additional women opted for counseling and testing despite ineligibility and none had mutations. Conclusions: A specialized program for young women facilitates appropriate referral for genetic testing and encourages high testing uptake, which is important given the high prevalence of mutations (28% of tested women). Further research is necessary to assess the psychological and management impact of having a VUS on young women compared to their older counterparts.

Knowledge and understanding of genetic test results in men undergoing multigene testing for inherited prostate cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1516-1516
Author(s):  
Veda N. Giri ◽  
Sarah Hegarty ◽  
Elias Obeid ◽  
Colette Hyatt ◽  
Carolyn Y Fang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Multivariable Analysis ◽  
Variant Of Uncertain Significance ◽  
Factors Associated ◽  
Genetic Test Results ◽  
Uncertain Significance ◽  
Significant Disagreement ◽  
Knowledge Of Cancer ◽  
Inherited Mutations

1516 Background: Genetic counseling (GC) for prostate cancer (PCA) risk is an emerging field, with limited insights regarding needs of males considering genetic testing (GT). Genetic Evaluation of Men is a prospective multigene testing study to identify inherited mutations linked to PCA, with testing following GC. We surveyed men pre-GT and post-GT on knowledge of cancer risk and genetics (KCRG) and understanding of personal GT results to identify GC needs. Methods: Eligibility for males affected or high-risk for PCA encompass age, race, family history (FH), and PCA stage/grade. Demographic, clinical, and FH data were obtained from participants and medical records. Pre-GT survey included questions on KCRG (15 items) and health literacy/numeracy (6 items). Post-GT survey additionally included understanding of GT results (9 items). Personal and FH were categorized into three hereditary cancer syndromes (HCS) linked to PCA. Factors associated with baseline KCRG were assessed by univariable models followed by multivariable linear regression. McNemar’s test was used to assess concordance of understanding GT results vs. actual results. Results: Among 109 men (mean age 63 years, 81% White, 59% PCA diagnosis) who completed pre- and post-surveys, factors associated with higher pre-test KCRG included meeting HCS criteria (p = 0.006) and higher numeracy (p = 0.025). On multivariable analysis, HCS remained significantly predictive of higher KCRG (p = 0.040). However, of 101 men who responded definitively regarding understanding of personal GT results, 13 responded incorrectly on mutation status indicating significant disagreement with actual results (McNemar’s p < 0.001). Of these 13 men, 12 had > = 1 variant of uncertain significance (VUS). Additionally, 6 men were unsure whether they carried a mutation when their GT results found VUS but no mutations. Conclusions: This is the first report of knowledge and understanding of genetics and cancer risk in the context of multigene testing for PCA. While personal/FH of HCS was associated with higher KCRG, understanding of personal GT results was lacking, and warrants tailored GC strategies for multigene testing for inherited PCA.

Prevalence of BRCA1/2 mutations among an Irish cohort unrestricted by testing eligibility thresholds.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13013-e13013
Author(s):  
Michael Conroy ◽  
David James Gallagher ◽  
Michael P. Farrell
Keyword(s):  
Genetic Testing ◽  
Brca1 Mutation ◽  
Brca2 Mutation ◽  
Diagnostic Testing ◽  
Retrospective Chart Review ◽  
Scoring Systems ◽  
National Guidelines ◽  
Variant Of Uncertain Significance ◽  
Uncertain Significance ◽  
Age Of Diagnosis

e13013 Background: Diagnostic criteria for BRCA1/2 genetic testing vary worldwide. Different eligibility thresholds for testing are used in different healthcare systems. In the public system in Ireland, this threshold is based on the Manchester Score (MS), with a score of ≥16 (approximately 10% likelihood of BRCA1/2 mutation) required for testing. Individuals unaffected by cancer are not eligible for diagnostic testing. Testing is also available privately by self-paying. We reviewed all self-pay patients in Ireland who were unrestricted by national guidelines. Methods: We performed a retrospective chart review of results from BRCA1/2 genetic testing in the Mater Private Hospital genetics clinic. Outcomes were recorded as ‘positive’, ‘wild type’ or ‘variant of uncertain significance’ (VUS). Results: 276 patients underwent testing between 2011 and 2016. 203 were affected with a median age of diagnosis of 48 (range 14-76), and 73 were unaffected individuals with a median age of 45 (range 30-74) at testing. 103 affected patients had a MS of ≥ 16: 7(6.8%) tested positive for BRCA1 mutation and 11(10.7%) tested positive for a BRCA2 mutation. Seven (6.8%) had a VUS characterised. 100 affected patients had an MS of <16: 3(3%) tested positive for a BRCA1 mutation and 5(5%)tested positive for a BRCA2 mutation. Eight (8%) had a VUS identified. 39 unaffected individuals had a MS ≥ 16: 6(15.4%) tested positive for a BRCA1 mutation, and 1(2.6%) for a BRCA2 mutation. 5(12.8%) had a VUS. 34 unaffected patients had an MS of <16: 2 (5.8%) tested positive for a BRCA2 mutation and 1 (2.9%) had a VUS. A total of 134 patients had a MS<16, and the prevalence of BRCA1/2 mutation in this group was 7% (n=10). Conclusions: The mutation detection rate was higher than expected in unaffected individuals and individuals belonging to families with MS < 16. Scoring systems such as the MS help to prioritise resources but miss many BRCA1/2 mutation carriers. [Table: see text]

scholarly journals Gaps in Receipt of Clinically Indicated Genetic Counseling After Diagnosis of Breast Cancer

2018 ◽  
Vol 36 (12) ◽  
pp. 1218-1224 ◽  
Author(s):  
Steven J. Katz ◽  
Kevin C. Ward ◽  
Ann S. Hamilton ◽  
M. Chandler Mcleod ◽  
Lauren P. Wallner ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Counseling ◽  
Los Angeles ◽  
Early Stage ◽  
Pathogenic Mutation ◽  
Variant Of Uncertain Significance ◽  
Younger Women ◽  
Genetic Test Results ◽  
Uncertain Significance ◽  
Risk Patients

Purpose Little is known about the extent to which genetic counseling is integrated into community practices for patients newly diagnosed with breast cancer. We examined the receipt of clinically indicated genetic counseling in these patients. Patients and Methods We surveyed 5,080 patients between the ages of 20 and 79 years, diagnosed from July 2013 to August 2015 with early-stage breast cancer and reported to the SEER registries of Georgia and Los Angeles County. Surveys were linked to SEER clinical data and genetic test results. The study sample (N = 1,711) comprised patients with indications for formal genetic risk evaluation. Results Overall, 47.4% did not get tested, 40.7% tested negative, 7.4% had a variant of uncertain significance only, and 4.5% had a pathogenic mutation. Three quarters (74.6%) received some form of genetic counseling (43.5%, formal counseling and 31.1%, physician-directed discussion). Virtually all tested patients (96.1%) reported some form of genetic discussion (62.2%, formal counseling and 33.9%, physician-directed discussion). However, only one half (50.6%) of those not tested received any discussion about genetics. Younger women were more likely to report some type of counseling, controlling for other factors: odds ratio, 4.5 (95% CI, 2.6 to 8.0); 1.9 (95% CI, 1.1 to 3.3); and 1.5 (95% CI, 1.0 to 2.3) for women younger than 50 years of age, 50 to 59 years of age, and 60 to 69 years of age versus those 70 years of age and older. Patients’ assessments of the amount of information they received about whether to get tested were similarly high whether they were counseled by a genetics expert or by a physician only (80.8% v 79.4% stated information was just right, P = .59). Conclusion Less than one half (43.5%) of patients with clinical indications received formal genetic counseling. There is a large gap between mandates for timely pretest formal genetic counseling in higher-risk patients and the reality of practice today.

Is the variant of uncertain significance (VUS) rate important in genetic testing for breast cancer?

2018 ◽  
Vol 44 (6) ◽  
pp. 875
Author(s):  
Gordon Wishart ◽  
Stewart Payne ◽  
Zoe Allen ◽  
Matthew Edwards ◽  
Vicki Kiesel
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Variant Of Uncertain Significance ◽  
Uncertain Significance

scholarly journals The Probability of Pathogenicity in Clinical Genetic Testing: A Solution for the Variant of Uncertain Significance

2016 ◽  
Vol 5 (4) ◽  
pp. 52
Author(s):  
Michael Gollob ◽  
Jeffrey S. Rosenthal ◽  
Kevin Thorpe
Keyword(s):  
Genetic Testing ◽  
Genetic Variant ◽  
Rare Variants ◽  
Direct Calculation ◽  
Medical Genetics ◽  
Clinical Genetic ◽  
Rare Genetic Variant ◽  
Variant Of Uncertain Significance ◽  
Clinical Genetic Testing ◽  
Uncertain Significance

We present a direct calculation for determining the probability that a rare genetic variant is the cause of an observed disease, under appropriate assumptions, in terms of the joint prevalence of the disease and of rare variants.  Our calculation provides a resolution of the so-called ``variant of unknown (or uncertain) significance'' problem, which has plagued medical genetics researchers.

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