Abstract
A growing number of physicians will interact with genetic test results as testing becomes more commonplace. While variants of uncertain significance can complicate results, it is equally important that physicians understand how to incorporate these results into clinical care. An online survey was created to assess physician self-reported comfort level with genetics and variants of uncertain significance. Physicians were asked to respond to three case examples involving genetic test results. The survey was sent to 488 physicians at Mayo Clinic FL on 8/16/2017. Physicians from all specialties were invited to participate. A total of 92 physicians responded to the survey. Only 13/84 (14.6%) responded to all three case examples with the answer deemed “most correct” by review of literature. Physicians that specialized in cancer were more likely to answer questions appropriately (P = .02). Around half (39/84) of the physicians incorrectly defined a variant of uncertain significance (VUS). Over 75% made a recommendation for genetic testing that was not warranted. Many physicians have never received formal genetics training; however, they will be expected to provide an accurate explanation of the genetic test results and subsequent evidence-based medical management recommendations. These results demonstrate that a substantial proportion of physicians lack a true understanding of the implications a VUS. Utilization of supplemental genetics training programs coupled with increase awareness of genetic services may help to improve patient care.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Moreno L (2016) Germline BRCA testing is moving from cancer risk assessment to a predictive biomarker for targeting cancer therapeutics. Clin Transl Oncol 18:981–987
Hudson KL, Murphy JA, Kaufman DJ, Javitt GH, Katsanis SH, Scott J (2006) Oversight of US genetic testing laboratories. Nat Biotechnol 24:1083–1090
Keating NL, Stoeckert KA, Regan MM, DiGianni L, Garber JE (2008) Physicians’ experiences with BRCA1/2 testing in community settings. J Clin Oncol 26:5789–5796
Shields AE, Burke W, Levy DE (2008) Differential use of available genetic tests among primary care physicians in the U.S.: results of a national survey. Genet Med 10:404–414
Richards S, Aziz N, Bale S et al (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17:405–424
Tung N, Lin NU, Kidd J et al (2016) Frequency of germline mutations in 25 cancer susceptibility genes in a sequential series of patients with breast cancer. J Clin Oncol 34:1460–1468
Eccles DM, Mitchell G, Monteiro AN et al (2015) BRCA1 and BRCA2 genetic testing-pitfalls and recommendations for managing variants of uncertain clinical significance. Ann Oncol 26:2057–2065
Hall MJ, Reid JE, Burbidge LA et al (2009) BRCA1 and BRCA2 mutations in women of different ethnicities undergoing testing for hereditary breast-ovarian cancer. Cancer 115:2222–2233
Garcia C (2014) Comparison of risk management strategies between women testing positive for a BRCA variant of unknown significance and women with known BRCA deleterious mutations. Genet Med 16:896–902
Culver JO (2013) Variants of uncertain significance in BRCA testing: evaluation of surgical decisions, risk perception, and cancer distress. Clin Genet 84:464–472
Welsh JL, Hoskin TL, Day CN et al (2017) Clinical decision making in patients with variant of uncertain significance in BRCA1 or BRCA2 genes. Ann Surg Oncol. https://doi.org/10.1245/s10434-017-5959-3
Kurian AW, Li Y, Hamilton AS et al (2017) Gaps in incorporating germline genetic testing into treatment decision-making for early-stage breast cancer. J Clin Oncol 35:2232–2239
Vos J, Otten W, van Asperen C, Jansen A, Menko F, Tibben A (2008) The counsellees’ view of an unclassified variant in BRCA1/2: recall, interpretation, and impact on life. Psycho-Oncology 17:822–830
Eccles BK, Copson E, Maishman T, Abraham JE, Eccles DM (2015) Understanding of BRCA VUS genetic test results by breast cancer specialists. BMC Cancer 15:936
Richer S, Haroun I, Graham TC, Eisen A, Kiss A, Warner E (2013) Variants of unknown significance in BRCA testing: impact on risk perception, worry, prevention and counseling. Ann Oncol 24:viii69–viii74
Greenblatt MS (2015) Sequence variants of uncertain significance: what to do when genetic test results are not definitive. Surg Oncol Clin N Am 24:833–846
Syngal S, Brand RE, Church JM, Giarddiello FM, Hampel HL, Burt RW (2015) ACG clinical guideline: genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol 110:223–263
Brierly KL (2010) Errors in delivery of cancer genetics services: implications for practice. Conn Med 74:413–423
Pruss D, Morris B, Hughes E et al (2014) Development and validation a new algorithm for the reclassification of genetic variants identified in the BRCA1 and BRCA2 genes. Breast Cancer Res Treat 47:119–132
Woodward ER, Sleightholme HV, Considine AM, Williamson S, McHugo JM, Cruger DG (2007) Annual surveillance by CA125 and transvaginal ultrasound for ovarian cancer in both high-risk and population risk women is ineffective. BJOG 114:1500–1509
Bond M, Pavey T, Welch K et al (2013) Systematic review of the psychological consquences of false-positive screening mammograms. Health Technol Assess 17:v–vi
Kruger J, Dunning D (1999) Unskilled and unaware of it: how difficulties in recognizing one’s own incompetence lead to inflated self-assessments. J Pers Soc Psychol 77:1121–1134
Mehdizadeh L, Sturrock A, Myers G, Khatib Y, Dacre J (2014) How well do doctors think they perform on the General Medical Council’s Tests of Competence pilot examinations? A cross-sectional study. BMJ Open 4:e004131
Daly MB, Pilarski R, Berry M et al (2017) Genetic/familial high-risk assessment: breast and ovarian, version 2.2017. NCCN Clin Pract Guidelines Oncol. https://www.nccn.org/professionals/physician_gls/pdf/genetics_screening.pdf. Accessed 8 Aug 2017
Riley BD, Culver JO, Skrzynia C et al (2012) Essential elements of genetic cancer risk assessment, counseling and testing: updated recommendations of the National Society of Genetic Counselors. J Genet Couns 21:151–161
Solomon I, Harrington E, Hooker G et al (2017) Lynch syndrome limbo: patient understanding of variants of uncertain significance. J Genet Couns 26:866–877
Najafzadeh M, Lynd LD, Davis JC et al (2012) Barriers to integrating personalized medicine into clinical practice: a best-worst scaling choice experiment. Genet Med 14:520–526
Talwar D, Tseng TS, Foster M, Xu L, Chen LS (2017) Genetics/genomics education for nongenetic health professionals: a systematic literature review. Genet Med 19:725–732
Delikurt T, Williamson GR, Anastasiadou V, Skirton H (2015) A systematic review of factors that act as barriers to patient referral to genetic services. Eur J Hum Genet 23:739–745
Haidle JL (2015) 2015 NSGC presidential address: gifts of genetic counselors: life’s leadership lessons. J Genet Couns 24:1–5
Vrecar I, Hristovski D, Peterlin B (2017) Telegenetics: an update on availability and use of telemedicine in clinical genetics service. J Med Syst 14:21
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no conflicts of interest, financial or otherwise.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Macklin, S.K., Jackson, J.L., Atwal, P.S. et al. Physician interpretation of variants of uncertain significance. Familial Cancer 18, 121–126 (2019). https://doi.org/10.1007/s10689-018-0086-2
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10689-018-0086-2