Article open access publication

Genetic Testing and Clinical Management Practices for Variants in Non-BRCA1/2 Breast (and Breast/Ovarian) Cancer Susceptibility Genes: An International Survey by the Evidence-Based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) Clinical Working Group

JCO Precision Oncology, American Society of Clinical Oncology (ASCO), ISSN 2473-4284

Volume 2, 2, 2018

DOI:10.1200/po.18.00091, Dimensions: pub.1107866706, PMC: PMC6742430, PMID: 31517176,



  1. (1) The University of Chicago Center for Clinical Cancer Genetics, Chicago, IL.
  2. (2) University of Southampton, grid.5491.9
  3. (3) Kuwait University, grid.411196.a
  4. (4) Hospital Universitari Vall d'Hebron, grid.411083.f
  5. (5) University of Rome Tor Vergata, grid.6530.0
  6. (6) Maastricht University Medical Centre, grid.412966.e
  7. (7) Azienda Ospedaliera Universitaria Pisana, grid.144189.1
  8. (8) IEO, European Institute of Oncology IRCCS.
  9. (9) University of Florence, grid.8404.8
  10. (10) Ospedale Cremona, Azienda Socio Sanitaria Territoriale (ASST) di Cremona, Cremona.
  11. (11) Hong Kong Sanatorium and Hospital, grid.414329.9
  12. (12) Ghent University Hospital, grid.410566.0
  13. (13) University of Modena and Reggio Emilia, grid.7548.e
  14. (14) Mayo Clinic, grid.66875.3a
  15. (15) Hospital Clínico San Carlos, grid.411068.a
  16. (16) Toma Advanced Biomedical Assays, Busto Arsizio.
  17. (17) University of Pennsylvania, grid.25879.31
  18. (18) Institute of Cancer Research, grid.18886.3f
  19. (19) Athens Medical Center, grid.431897.0
  20. (20) National Centre of Scientific Research Demokritos, grid.6083.d
  21. (21) University of Utah, grid.223827.e
  22. (22) Cyprus Institute of Neurology and Genetics, grid.417705.0
  23. (23) Rigshospitalet, grid.475435.4, Capital Region
  24. (24) Keio University, grid.26091.3c
  25. (25) Paris Descartes University, grid.10992.33
  26. (26) Charles University, grid.4491.8
  27. (27) Normandie Université, grid.460771.3
  28. (28) Catalan Institute of Oncology, grid.418701.b
  29. (29) Fondazione IRCCS Istituto Nazionale dei Tumori, grid.417893.0
  30. (30) Radboud University Nijmegen Medical Centre, grid.10417.33
  31. (31) Leiden University Medical Center, grid.10419.3d
  32. (32) Moffitt Cancer Center, grid.468198.a
  33. (33) University of Brescia, grid.7637.5
  34. (34) Prince of Wales Hospital, grid.415193.b
  35. (35) Ospedale di Parma, grid.411482.a
  36. (36) Odense University Hospital, grid.7143.1, Southern Denmark Region
  37. (37) King Edward Memorial Hospital, grid.415259.e
  38. (38) Hospital de Câncer de Barretos, grid.427783.d
  39. (39) Aalborg Hospital, grid.27530.33, North Denmark Region
  40. (40) Sapienza University of Rome, grid.7841.a
  41. (41) Azienda Ospedaliera di Cosenza, grid.452249.c
  42. (42) Memorial Sloan Kettering Cancer Center, grid.51462.34
  43. (43) National Research Council, grid.5326.2
  44. (44) University of Buenos Aires, grid.7345.5
  45. (45) Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, grid.419563.c
  46. (46) Portuguese Oncology Institute, grid.418711.a
  47. (47) Ospedale di Circolo e Fondazione Macchi, grid.412972.b
  48. (48) The Ohio State University, grid.261331.4
  49. (49) Lund University, grid.4514.4
  50. (50) Dana-Farber Cancer Institute, grid.65499.37
  51. (51) Ospedale Policlinico San Martino IRCCS per l'Oncologia, Genoa.
  52. (52) University of Santiago de Compostela, grid.11794.3a
  53. (53) Women's and Children's NHS Foundation Trust, Birmingham, United Kingdom.
  54. (54) University Hospital Cologne, grid.411097.a
  55. (55) City Of Hope National Medical Center, grid.410425.6
  56. (56) QIMR Berghofer Medical Research Institute, grid.1049.c
  57. (57) Istituto Oncologico Veneto, grid.419546.b


Purpose: To describe a snapshot of international genetic testing practices, specifically regarding the use of multigene panels, for hereditary breast/ovarian cancers. We conducted a survey through the Evidence-Based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) consortium, covering questions about 16 non-BRCA1/2 genes. Methods: Data were collected via in-person and paper/electronic surveys. ENIGMA members from around the world were invited to participate. Additional information was collected via country networks in the United Kingdom and in Italy. Results: Responses from 61 cancer genetics practices across 20 countries showed that 16 genes were tested by > 50% of the centers, but only six (PALB2, TP53, PTEN, CHEK2, ATM, and BRIP1) were tested regularly. US centers tested the genes most often, whereas United Kingdom and Italian centers with no direct ENIGMA affiliation at the time of the survey were the least likely to regularly test them. Most centers tested the 16 genes through multigene panels; some centers tested TP53, PTEN, and other cancer syndrome-associated genes individually. Most centers reported (likely) pathogenic variants to patients and would test family members for such variants. Gene-specific guidelines for breast and ovarian cancer risk management were limited and differed among countries, especially with regard to starting age and type of imaging and risk-reducing surgery recommendations. Conclusion: Currently, a small number of genes beyond BRCA1/2 are routinely analyzed worldwide, and management guidelines are limited and largely based on expert opinion. To attain clinical implementation of multigene panel testing through evidence-based management practices, it is paramount that clinicians (and patients) participate in international initiatives that share panel testing data, interpret sequence variants, and collect prospective data to underpin risk estimates and evaluate the outcome of risk intervention strategies.


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Field Citation Ratio (FCR): 3.13

Relative Citation ratio (RCR): 0.6

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Green, Accepted