Germline Genetic Testing: What the Breast Surgeon Needs to Know

Abstract

Purpose

The American Society of Breast Surgeons (ASBrS) sought to provide educational guidelines for breast surgeons on how to incorporate genetic information and genomics into their practice.

Methods

A comprehensive nonsystematic review was performed of selected peer-reviewed literature. The Genetics Working Group of the ASBrS convened to develop guideline recommendations.

Results

Clinical and educational guidelines were prepared to outline the essential knowledge for breast surgeons to perform germline genetic testing and to incorporate the findings into their practice, which have been approved by the ASBrS Board of Directors.

Recommendations

Thousands of women in the USA would potentially benefit from genetic testing for BRCA1, BRCA2, and other breast cancer genes that markedly increase their risk of developing breast cancer. As genetic testing is now becoming more widely available, women should be made aware of these tests and consider testing. Breast surgeons are well positioned to help facilitate this process. The areas where surgeons need to be knowledgeable include: (1) identification of patients for initial breast cancer-related genetic testing, (2) identification of patients who tested negative in the past but now need updated testing, (3) initial cancer genetic testing, (4) retesting of patients who need their genetic testing updated, (5) cancer genetic test interpretation, posttest counseling and management, (6) management of variants of uncertain significance, (7) cascade genetic testing, (8) interpretation of genetic tests other than clinical cancer panels and the counseling and management required, and (9) interpretation of somatic genetic tests and the counseling and management required.

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References

  1. 1.

    Hughes KS. Genetic testing: what problem are we trying to solve? J Clin Oncol. 2017;35(34):3789–91.

    Article  PubMed  Google Scholar 

  2. 2.

    Daly MB, Pilarski R, Berry MP, et al. NCCN Clinical Practice Guidelines in Oncology: Genetic/Familial High-Risk Assessment: Breast and Ovarian. National Comprehensive Cancer Network; July 30, 2018.

  3. 3.

    2014 Professional Status Survey: Executive Summary. 2014.

  4. 4.

    Noll A, Parekh JP, Zhou M, et al. Barriers to Llynch syndrome testing and preoperative result availability in early-onset colorectal cancer: a National Physician Survey study. Clin Transl Gastroenterol. 2018; 9(9):185.

    Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Hoskovec JM, Bennett RL, Carey ME, et al. Projecting the supply and demand for certified genetic counselors: a workforce study. J Genet Couns. 2018;27(1):16–20.

    Article  PubMed  Google Scholar 

  6. 6.

    Childers KK, Maggard-Gibbons M, Macinko J, Childers CP. National distribution of cancer genetic testing in the United States: evidence for a gender disparity in hereditary breast and ovarian cancer. JAMA Oncol. 2018;4(6):876–79.

    Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Childers CP, Childers KK, Maggard-Gibbons M, Macinko J. National estimates of genetic testing in women with a history of breast or ovarian cancer. J Clin Oncol. 2017;35(34):3800–06.

    Article  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Chen Z, Kolor K, Grosse SD, et al. Trends in utilization and costs of BRCA testing among women aged 18–64 years in the United States, 2003–2014. Genet Med. 2018;20(4):428–34.

    Article  PubMed  Google Scholar 

  9. 9.

    Manickam K, Buchanan AH, Schwartz MB, et al. Exome sequencing–based screening for BRCA1/2 expected pathogenic variants among adult biobank participants. JAMA Netw Open. 2018;1(5):e182140.

    Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Drohan B, Roche CA, Cusack JC, Jr., Hughes KS. Hereditary breast and ovarian cancer and other hereditary syndromes: using technology to identify carriers. Ann Surg Oncol. 2012;19(6):1732–37.

    Article  PubMed  Google Scholar 

  11. 11.

    Hall MJ, Olopade OI. Disparities in genetic testing: thinking outside the BRCA box. J Clin Oncol. 2006;24(14):2197–2203.

    Article  PubMed  Google Scholar 

  12. 12.

    Forman AD, Hall MJ. Influence of race/ethnicity on genetic counseling and testing for hereditary breast and ovarian cancer. Breast J. 2009;15 Suppl 1:S56–62.

    Article  PubMed  Google Scholar 

  13. 13.

    Halbert CH, Kessler LJ, Mitchell E. Genetic testing for inherited breast cancer risk in African Americans. Cancer Invest. 2005;23(4):285–95.

    Article  PubMed  Google Scholar 

  14. 14.

    Beitsch PD, Whitworth PW, Hughes K, et al. Underdiagnosis of hereditary breast cancer: are genetic testing guidelines a tool or an obstacle? J Clin Oncol. 2018:Jco1801631.

  15. 15.

    Guidelines miss cancer patients who could benefit from genetic testing: Part 1. In: Perspectives in Genetics: Empowering the Medical Community through Education and Insight. Vol 2018. Online: Invitae; 2018.

  16. 16.

    Syngal S, Furniss C. Germline genetic testing for pancreatic ductal adenocarcinoma at time of diagnosis. JAMA. 2018;319(23):2383–85.

    Article  PubMed  Google Scholar 

  17. 17.

    Pritchard CC, Mateo J, Walsh MF, et al. Inherited DNA-repair gene mutations in men with metastatic prostate cancer. N Engl J Med. 2016;375(5):443–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Guo X, Shi J, Cai Q, et al. Use of deep whole-genome sequencing data to identify structure risk variants in breast cancer susceptibility genes. Hum Mol Genet. 2018;27(5):853–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Park S, Supek F, Lehner B. Systematic discovery of germline cancer predisposition genes through the identification of somatic second hits. Nat Commun. 2018;9(1):2601.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Liang X, Vacher S, Boulai A, et al. Targeted next-generation sequencing identifies clinically relevant somatic mutations in a large cohort of inflammatory breast cancer. Breast Cancer Res. 2018;20(1):88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Kurian AW, Li Y, Hamilton AS, et al. Gaps in incorporating germline genetic testing into treatment decision-making for early-stage breast cancer. J Clin Oncol. 2017;35(20):2232–39.

    Article  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Trivers KF, Baldwin LM, Miller JW, et al. Reported referral for genetic counseling or BRCA 1/2 testing among United States physicians: a vignette-based study. Cancer. 2011;117(23):5334–43.

    Article  PubMed  Google Scholar 

  23. 23.

    Morman NA, Byrne L, Collins C, Reynolds K, Bell JG. Breast cancer risk assessment at the time of screening mammography: perceptions and clinical management outcomes for women at high risk. J Genet Couns. 2017;26(4):776–84.

    Article  PubMed  Google Scholar 

  24. 24.

    Tung N, Lin NU, Kidd J, et al. Frequency of germline mutations in 25 cancer susceptibility genes in a sequential series of patients with breast cancer. J Clin Oncol. 2016;34(13):1460–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Maxwell KN, Wubbenhorst B, D’Andrea K, et al. Prevalence of mutations in a panel of breast cancer susceptibility genes in BRCA1/2-negative patients with early-onset breast cancer. Genet Med. 2015;17(8):630–38.

    Article  CAS  PubMed  Google Scholar 

  26. 26.

    Desmond A, Kurian AW, Gabree M, et al. Clinical actionability of multigene panel testing for hereditary breast and ovarian cancer risk assessment. JAMA Oncol. 2015;1(7):943–51.

    Article  PubMed  Google Scholar 

  27. 27.

    Whitworth P, Beitsch P, Arnell C, et al. Impact of payer constraints on access to genetic testing. J Oncol Pract. 2017;13(1):e47–56.

    Article  PubMed  Google Scholar 

  28. 28.

    Stenehjem DD, Au T, Sainski AM, et al. Impact of a genetic counseling requirement prior to genetic testing. BMC Health Serv Res. 2018;18(1):165.

    Article  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Consensus Guideline on Hereditary Genetic Testing for Patients with and without Breast Cancer 2017. https://www.breastsurgeons.org/about/statements/PDF_Statements/BRCA_Testing.pdf. Accessed 13 Aug 2018.

  30. 30.

    National Accreditation Program for Breast Centers Standards Manual; 2018 edition (2018). https://accreditation.facs.org/accreditationdocuments/NAPBC/Portal%20Resources/2018NAPBCStandardsManual.pdf. Accessed 13 Aug 2018.

  31. 31.

    Robson ME, Bradbury AR, Arun B, et al. American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility. J Clin Oncol. 2015;33(31):3660–67.

    Article  CAS  PubMed  Google Scholar 

  32. 32.

    Code of Medical Ethics Opinion 4.1.1—Genetic Testing & Counseling. https://www.ama-assn.org/delivering-care/genetic-testing-counseling. Accessed 13 Aug 2018.

  33. 33.

    Agnese DM, Pollock RE. Breast cancer genetic counseling: a surgeon’s perspective. Front Surg. 2016;3:4.

    Article  PubMed  PubMed Central  Google Scholar 

  34. 34.

    Beitsch PD, Whitworth PW. Can breast surgeons provide breast cancer genetic testing? An American Society of Breast Surgeons survey. Ann Surg Oncol. 2014;21(13):4104–08.

    Article  PubMed  Google Scholar 

  35. 35.

    Hughes KS. Personal community with Myriad Genetics. In: Kevin Hughes M (ed); 2018.

  36. 36.

    Hughes KS, Parmigiani G, Braun DP. All Syndromes Known to Man Evaluator. 2018; www.ask2me.org. Accessed 8/13/2018.

  37. 37.

    Slavin TP, Van Tongeren LR, Behrendt CE, et al. Prospective study of cancer genetic variants: variation in rate of reclassification by ancestry. J Natl Cancer Inst. 2018.

  38. 38.

    Augusto BM, Lake P, Scherr CL, Couch FJ, Lindor NM, Vadaparampil ST. From the laboratory to the clinic: sharing BRCA VUS reclassification tools with practicing genetics professionals. J Commun Genet. 2018;9(3):209–15.

    Article  Google Scholar 

  39. 39.

    Roberts MC, Dotson WD, DeVore CS, et al. Delivery of cascade screening for hereditary conditions: a scoping review of the literature. Health Affairs (Project Hope). 2018;37(5):801–08.

    Article  Google Scholar 

  40. 40.

    Katapodi MC, Jung M, Schafenacker AM, et al. Development of a Web-based family intervention for BRCA carriers and their biological relatives: acceptability, feasibility, and usability study. JMIR Cancer. 2018;4(1):e7.

    Article  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Nilsson MP, Emmertz M, Kristoffersson U, et al. Germline mutations in BRCA1 and BRCA2 incidentally revealed in a biobank research study: experiences from re-contacting mutation carriers and relatives. J Community Genet. 2018;9(3):201–08.

    Article  Google Scholar 

  42. 42.

    Buchanan AH, Manickam K, Meyer MN, et al. Early cancer diagnoses through BRCA1/2 screening of unselected adult biobank participants. Genet Med. 2018;20(5):554–8.

    Article  CAS  PubMed  Google Scholar 

  43. 43.

    Mandelker D, Zhang L, Kemel Y, et al. Mutation detection in patients with advanced cancer by universal sequencing of cancer-related genes in tumor and normal DNA vs guideline-based germline testing. JAMA. 2017;318(9):825–35.

    Article  PubMed  PubMed Central  Google Scholar 

  44. 44.

    The American Society of Breast Surgeons Mastery of Breast Surgery (2018). https://www.breastsurgeons.org/programs/mastery/index.php. Accessed 13 Aug 2018.

  45. 45.

    Pritzlaff M, Yorczyk A, Robinson LS, et al. An internal performance assessment of CancerGene Connect: an electronic tool to streamline, measure and improve the genetic counseling process. J Genet Couns. 2014;23(6):1034–44.

    Article  PubMed  PubMed Central  Google Scholar 

  46. 46.

    CRA Health. 2018; www.crahealth.com. Accessed 9/30/2018.

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Disclosures

Dr. Hughes receives Honoraria from Focal Therapeutics (surgical implant for radiation planning with breast conservation), 23andMe, and is a founder of and has a financial interest in CRA Health (formerly Hughes RiskApps). Dr. Hughes’ interests were reviewed and are managed by Massachusetts General Hospital and Partners Health Care in accordance with their conflict of interest policies. Dr. Plichta has received grant funding from the Color Foundation (9/2017–10/2018).

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Correspondence to Kevin S. Hughes MD.

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Plichta, J.K., Sebastian, M.L., Smith, L.A. et al. Germline Genetic Testing: What the Breast Surgeon Needs to Know. Ann Surg Oncol 26, 2184–2190 (2019). https://doi.org/10.1245/s10434-019-07341-8

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