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

S. Nielsen, Iris L. Romero, Olufunmilayo I. Olopade, Diana Eccles, Ros Eeles, Yvonne Wallis, Fahd Al-Mulla, Judith Balmana, Orland Diez, Miguel De La Hoya, Conxi Lazaro, Ana Vega, Michela Biancolella, Maria Piane, Maria Caligo, Gabriele L. Capone, Pietro Cavalli, Laura Cortesi, Simona de Toffol, Luigi MoriNadia Naldi, Marianna Puzzo, Maria Christina Sini, Gianluca Tedaldi, Maria Grazia Tibiletti, Liliana Varesco, Arcangela De Nicolo, Marinus Blok, Encarna Gomez Garcia, Arjen R. Mensenkamp, Setareh Moghadasi, T.L. Chris Chan, Kathleen B. M. Claes, Fergus Couch, Susan M. Domchek, Anna Efremidis, Florentia Fostira, David E. Goldgar, A. Hadjisavvas, Maria Loizidou, Maria Rossing, Henriette Roed Nielsen, Mads Thomassen, Inge Sokilde Pedersen, Akira Hirasawa, Claude Houdayer, Sophie Krieger, Petra Kleiblova, Jana Soukupova, Alvaro N. Monteiro, April Morrow, Nicholas S. Pachter, Amanda B. Spurdle, E.I. Palmero, Mark Robson, Angela R. Solano, Manuel R. Teixeira, Amanda E. Toland, Therese Törngren, Erica Vaccari, Barbara Wappenschmidt, Jeffrey N. Weitzel

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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. (C) 2018 by American Society of Clinical Oncology

Original languageEnglish
Pages (from-to)1-43
Number of pages43
JournalJCO Precision Oncology
Volume2
DOIs
Publication statusPublished - 26 Oct 2018

Keywords

  • HEREDITARY BREAST
  • INHERITED MUTATIONS
  • GENOMIC CAPTURE
  • OVARIAN
  • PANEL
  • RISK
  • PREDISPOSITION
  • CLASSIFICATION
  • GUIDELINES
  • FAMILIES

Cite this

Nielsen, S., Romero, I. L., Olopade, O. I., Eccles, D., Eeles, R., Wallis, Y., Al-Mulla, F., Balmana, J., Diez, O., De La Hoya, M., Lazaro, C., Vega, A., Biancolella, M., Piane, M., Caligo, M., Capone, G. L., Cavalli, P., Cortesi, L., de Toffol, S., ... Weitzel, J. N. (2018). 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, 2, 1-43. https://doi.org/10.1200/PO.18.00091