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, Sarah M.
AU - Eccles, Diana M.
AU - Romero, Iris L.
AU - Al-Mulla, Fahd
AU - Balmaña, Judith
AU - Biancolella, Michela
AU - Blok, Rien
AU - Caligo, Maria Adelaide
AU - Calvello, Mariarosaria
AU - Capone, Gabriele Lorenzo
AU - Cavalli, Pietro
AU - Chan, T.L. Chris
AU - Claes, Kathleen B.M.
AU - Cortesi, Laura
AU - Couch, Fergus J.
AU - de la Hoya, Miguel
AU - De Toffol, Simona
AU - Diez, Orland
AU - Domchek, Susan M.
AU - Eeles, Ros
AU - Efremidis, Anna
AU - Fostira, Florentia
AU - Goldgar, David
AU - Hadjisavvas, Andreas
AU - Hansen, Thomas v.O.
AU - Hirasawa, Akira
AU - Houdayer, Claude
AU - Kleiblova, Petra
AU - Krieger, Sophie
AU - Lázaro, Conxi
AU - Loizidou, Maria
AU - Manoukian, Siranoush
AU - Mensenkamp, Arjen R.
AU - Moghadasi, Setareh
AU - Monteiro, Alvaro N.
AU - Mori, Luigi
AU - Morrow, April
AU - Naldi, Nadia
AU - Nielsen, Henriette R.
AU - Olopade, Olufunmilayo I.
AU - Pachter, Nicholas S.
AU - Palmero, Edenir I.
AU - Pedersen, Inge S.
AU - Piane, Maria
AU - Puzzo, Marianna
AU - Robson, Mark
AU - Rossing, Maria
AU - Sini, Maria Christina
AU - Solano, Angela
AU - Soukupova, Jana
AU - Tedaldi, Gianluca
AU - Teixeira, Manuel
AU - Thomassen, Mads
AU - Tibiletti, Maria Grazia
AU - Toland, Amanda
AU - Törngren, Therese
AU - Vaccari, Erica
AU - Varesco, Liliana
AU - Vega, Ana
AU - Wallis, Yvonne
AU - Wappenschmidt, Barbara
AU - Weitzel, Jeffrey
AU - Spurdle, Amanda B.
AU - De Nicolo, Arcangela
AU - Gómez-García, Encarna B.
PY - 2018/10/26
Y1 - 2018/10/26
N2 - PurposeTo 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.MethodsData 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.ResultsResponses 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.ConclusionCurrently, 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.
AB - PurposeTo 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.MethodsData 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.ResultsResponses 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.ConclusionCurrently, 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.
U2 - 10.1200/PO.18.00091
DO - 10.1200/PO.18.00091
M3 - Journal article
SN - 2473-4284
VL - 2
JO - JCO Precision Oncology
JF - JCO Precision Oncology
ER -