TY - JOUR
T1 - Genetic Testing and Clinical Management Practices for Variants in Non-BRCA1/2 Breast (and Breast/Ovarian) Cancer Susceptibility Genes
T2 - An International Survey by the Evidence-Based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) Clinical Working Group
AU - Nielsen, S.
AU - Romero, Iris L.
AU - Olopade, Olufunmilayo I.
AU - Eccles, Diana
AU - Eeles, Ros
AU - Wallis, Yvonne
AU - Al-Mulla, Fahd
AU - Balmana, Judith
AU - Diez, Orland
AU - De La Hoya, Miguel
AU - Lazaro, Conxi
AU - Vega, Ana
AU - Biancolella, Michela
AU - Piane, Maria
AU - Caligo, Maria
AU - Capone, Gabriele L.
AU - Cavalli, Pietro
AU - Cortesi, Laura
AU - de Toffol, Simona
AU - Mori, Luigi
AU - Naldi, Nadia
AU - Puzzo, Marianna
AU - Sini, Maria Christina
AU - Tedaldi, Gianluca
AU - Tibiletti, Maria Grazia
AU - Varesco, Liliana
AU - De Nicolo, Arcangela
AU - Blok, Marinus
AU - Gómez-García, Encarna B.
AU - Mensenkamp, Arjen R.
AU - Moghadasi, Setareh
AU - Chan, T.L. Chris
AU - Claes, Kathleen B. M.
AU - Couch, Fergus
AU - Domchek, Susan M.
AU - Efremidis, Anna
AU - Fostira, Florentia
AU - Goldgar, David E.
AU - Hadjisavvas, A.
AU - Loizidou, Maria
AU - Rossing, Maria
AU - Roed Nielsen, Henriette
AU - Thomassen, Mads
AU - Pedersen, Inge Sokilde
AU - Hirasawa, Akira
AU - Houdayer, Claude
AU - Krieger, Sophie
AU - Kleiblova, Petra
AU - Soukupova, Jana
AU - Monteiro, Alvaro N.
AU - Morrow, April
AU - Pachter, Nicholas S.
AU - Spurdle, Amanda B.
AU - Palmero, E.I.
AU - Robson, Mark
AU - Solano, Angela R.
AU - Teixeira, Manuel R.
AU - Toland, Amanda E.
AU - Törngren, Therese
AU - Vaccari, Erica
AU - Wappenschmidt, Barbara
AU - Weitzel, Jeffrey N.
PY - 2018/10/26
Y1 - 2018/10/26
N2 - 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
AB - 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
KW - HEREDITARY BREAST
KW - INHERITED MUTATIONS
KW - GENOMIC CAPTURE
KW - OVARIAN
KW - PANEL
KW - RISK
KW - PREDISPOSITION
KW - CLASSIFICATION
KW - GUIDELINES
KW - FAMILIES
U2 - 10.1200/PO.18.00091
DO - 10.1200/PO.18.00091
M3 - Article
C2 - 31517176
SN - 2473-4284
VL - 2
SP - 1
EP - 43
JO - JCO Precision Oncology
JF - JCO Precision Oncology
ER -