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

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 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.

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.

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 Genetic Testing to Guide Risk-Stratified Screens for Breast Cancer

2019 ◽  
Vol 9 (1) ◽  
pp. 15 ◽  
Author(s):  
Ava Willoughby ◽  
Paul Andreassen ◽  
Amanda Toland
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Genetic Testing ◽  
High Risk ◽  
Cancer Susceptibility ◽  
Cancer Surveillance ◽  
Risk Scores ◽  
Breast And Ovarian Cancer ◽  
Cancer Susceptibility Genes ◽  
Uncertain Significance

Breast cancer screening modalities and guidelines continue to evolve and are increasingly based on risk factors, including genetic risk and a personal or family history of cancer. Here, we review genetic testing of high-penetrance hereditary breast and ovarian cancer genes, including BRCA1 and BRCA2, for the purpose of identifying high-risk individuals who would benefit from earlier screening and more sensitive methods such as magnetic resonance imaging. We also consider risk-based screening in the general population, including whether every woman should be genetically tested for high-risk genes and the potential use of polygenic risk scores. In addition to enabling early detection, the results of genetic screens of breast cancer susceptibility genes can be utilized to guide decision-making about when to elect prophylactic surgeries that reduce cancer risk and the choice of therapeutic options. Variants of uncertain significance, especially missense variants, are being identified during panel testing for hereditary breast and ovarian cancer. A finding of a variant of uncertain significance does not provide a basis for increased cancer surveillance or prophylactic procedures. Given that variant classification is often challenging, we also consider the role of multifactorial statistical analyses by large consortia and functional tests for this purpose.

scholarly journals Genetic testing for breast cancer risk, from BRCA1/2 to a seven gene panel: an ethical analysis

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Erik Gustavsson ◽  
Giovanni Galvis ◽  
Niklas Juth
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Cost Effectiveness ◽  
Gene Panel ◽  
Special Focus ◽  
Secondary Findings ◽  
Variants Of Uncertain Significance ◽  
Pathogenic Variants ◽  
Increased Risk ◽  
Uncertain Significance

Abstract Background Genetic testing is moving from targeted investigations of monogenetic diseases to broader testing that may provide more information. For example, recent health economic studies of genetic testing for an increased risk of breast cancer suggest that it is associated with higher cost-effectiveness to screen for pathogenic variants in a seven gene panel rather than the usual two gene test for variants in BRCA1 and BRCA2. However, irrespective of the extent to which the screening of the panel is cost-effective, there may be ethical reasons to not screen for pathogenic variants in a panel, or to revise the way in which testing and disclosing of results are carried out. Main text In this paper we discuss the ethical aspects of genetic testing for an increased risk of breast cancer with a special focus on the ethical differences between screening for pathogenic variants in BRCA1/2 and a seven gene panel. The paper identifies that the panel increases the number of secondary findings as well as the number of variants of uncertain significance as two specific issues that call for ethical reflection. Conclusions We conclude that while the problem of handling secondary findings should not be overstated with regard to the panel, the fact that the panel also generate more variants of uncertain significance, give rise to a more complex set of problems that relate to the value of health as well as the value of autonomy. Therefore, it is insufficient to claim that the seven gene panel is preferable by only referring to the higher cost effectiveness of the panel.

Time Trends in Receipt of Germline Genetic Testing and Results for Women Diagnosed With Breast Cancer or Ovarian Cancer, 2012-2019

2021 ◽  
pp. JCO.20.02785
Author(s):  
Allison W. Kurian ◽  
Kevin C. Ward ◽  
Paul Abrahamse ◽  
Irina Bondarenko ◽  
Ann S. Hamilton ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Genetic Testing ◽  
Ovarian Cancer Risk ◽  
Test Results ◽  
Pathogenic Variants ◽  
Uncertain Significance ◽  
Hispanic White ◽  
Cancer Risk Reduction ◽  
Gene Category

PURPOSE Genetic testing is important for breast and ovarian cancer risk reduction and treatment, yet little is known about its evolving use. METHODS SEER records of women of age ≥ 20 years diagnosed with breast or ovarian cancer from 2013 to 2017 in California or Georgia were linked to the results of clinical germline testing through 2019. We measured testing trends, rates of variants of uncertain significance (VUS), and pathogenic variants (PVs). RESULTS One quarter (25.2%) of 187,535 patients with breast cancer and one third (34.3%) of 14,689 patients with ovarian cancer were tested; annually, testing increased by 2%, whereas the number of genes tested increased by 28%. The prevalence of test results by gene category for breast cancer cases in 2017 were BRCA1/2 , PVs 5.2%, and VUS 0.8%; breast cancer–associated genes or ovarian cancer–associated genes ( ATM, BARD1, BRIP1, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, NBN, NF1, PALB2, PMS2, PTEN, RAD51C, RAD51D, STK11, and TP53), PVs 3.7%, and VUS 12.0%; other actionable genes ( APC, BMPR1A, MEN1, MUTYH, NF2, RB1, RET, SDHAF2, SDHB, SDHC, SDHD, SMAD4, TSC1, TSC2, and VHL) PVs 0.6%, and VUS 0.5%; and other genes, PVs 0.3%, and VUS 2.6%. For ovarian cancer cases in 2017, the prevalence of test results were BRCA1/2, PVs 11.0%, and VUS 0.9%; breast or ovarian genes, PVs 4.0%, and VUS 12.6%; other actionable genes, PVs 0.7%, and VUS 0.4%; and other genes, PVs 0.3%, and VUS 0.6%. VUS rates doubled over time (2013 diagnoses: 11.2%; 2017 diagnoses: 26.8%), particularly for racial or ethnic minorities (47.8% Asian and 46.0% Black, v 24.6% non-Hispanic White patients; P < .001). CONCLUSION A testing gap persists for patients with ovarian cancer (34.3% tested v nearly all recommended), whereas adding more genes widened a racial or ethnic gap in VUS results. Most PVs were in 20 breast cancer–associated genes or ovarian cancer–associated genes; testing other genes yielded mostly VUS. Quality improvement should focus on testing indicated patients rather than adding more genes.

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.

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