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Familial Cancer

, Volume 18, Issue 1, pp 121–126 | Cite as

Physician interpretation of variants of uncertain significance

  • Sarah K. MacklinEmail author
  • Jessica L. Jackson
  • Paldeep S. Atwal
  • Stephanie L. Hines
Original Article

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.

Keywords

Genetics Cancer surveillance Variant of uncertain significance 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest, financial or otherwise.

Supplementary material

10689_2018_86_MOESM1_ESM.docx (16 kb)
Supplementary material 1 (DOCX 15 KB)

References

  1. 1.
    Moreno L (2016) Germline BRCA testing is moving from cancer risk assessment to a predictive biomarker for targeting cancer therapeutics. Clin Transl Oncol 18:981–987CrossRefGoogle Scholar
  2. 2.
    Hudson KL, Murphy JA, Kaufman DJ, Javitt GH, Katsanis SH, Scott J (2006) Oversight of US genetic testing laboratories. Nat Biotechnol 24:1083–1090CrossRefGoogle Scholar
  3. 3.
    Keating NL, Stoeckert KA, Regan MM, DiGianni L, Garber JE (2008) Physicians’ experiences with BRCA1/2 testing in community settings. J Clin Oncol 26:5789–5796CrossRefGoogle Scholar
  4. 4.
    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 10:404–414CrossRefGoogle Scholar
  5. 5.
    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 17:405–424CrossRefGoogle Scholar
  6. 6.
    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 34:1460–1468CrossRefGoogle Scholar
  7. 7.
    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 26:2057–2065CrossRefGoogle Scholar
  8. 8.
    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 115:2222–2233CrossRefGoogle Scholar
  9. 9.
    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 16:896–902CrossRefGoogle Scholar
  10. 10.
    Culver JO (2013) Variants of uncertain significance in BRCA testing: evaluation of surgical decisions, risk perception, and cancer distress. Clin Genet 84:464–472CrossRefGoogle Scholar
  11. 11.
    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 Google Scholar
  12. 12.
    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 35:2232–2239CrossRefGoogle Scholar
  13. 13.
    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 17:822–830CrossRefGoogle Scholar
  14. 14.
    Eccles BK, Copson E, Maishman T, Abraham JE, Eccles DM (2015) Understanding of BRCA VUS genetic test results by breast cancer specialists. BMC Cancer 15:936CrossRefGoogle Scholar
  15. 15.
    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–viii74Google Scholar
  16. 16.
    Greenblatt MS (2015) Sequence variants of uncertain significance: what to do when genetic test results are not definitive. Surg Oncol Clin N Am 24:833–846CrossRefGoogle Scholar
  17. 17.
    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 110:223–263CrossRefGoogle Scholar
  18. 18.
    Brierly KL (2010) Errors in delivery of cancer genetics services: implications for practice. Conn Med 74:413–423Google Scholar
  19. 19.
    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 47:119–132CrossRefGoogle Scholar
  20. 20.
    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 114:1500–1509CrossRefGoogle Scholar
  21. 21.
    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–viCrossRefGoogle Scholar
  22. 22.
    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 77:1121–1134CrossRefGoogle Scholar
  23. 23.
    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:e004131CrossRefGoogle Scholar
  24. 24.
    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
  25. 25.
    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 21:151–161CrossRefGoogle Scholar
  26. 26.
    Solomon I, Harrington E, Hooker G et al (2017) Lynch syndrome limbo: patient understanding of variants of uncertain significance. J Genet Couns 26:866–877CrossRefGoogle Scholar
  27. 27.
    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 14:520–526CrossRefGoogle Scholar
  28. 28.
    Talwar D, Tseng TS, Foster M, Xu L, Chen LS (2017) Genetics/genomics education for nongenetic health professionals: a systematic literature review. Genet Med 19:725–732CrossRefGoogle Scholar
  29. 29.
    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 23:739–745CrossRefGoogle Scholar
  30. 30.
    Haidle JL (2015) 2015 NSGC presidential address: gifts of genetic counselors: life’s leadership lessons. J Genet Couns 24:1–5CrossRefGoogle Scholar
  31. 31.
    Vrecar I, Hristovski D, Peterlin B (2017) Telegenetics: an update on availability and use of telemedicine in clinical genetics service. J Med Syst 14:21CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Clinical GenomicsMayo ClinicJacksonvilleUSA
  2. 2.Department of Medicine, Department of General Internal MedicineMayo ClinicJacksonvilleUSA

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