@article{9232696c24c64fe18a4a5f97a8aeaf74,
title = "Performance of BRCA1/2 mutation prediction models in male breast cancer patients",
abstract = "To establish whether existing mutation prediction models can identify which male breast cancer (MBC) patients should be offered BRCA1 and BRCA2 diagnostic DNA screening, we compared the performance of BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm), BRCAPRO (BRCA probability) and the Myriad prevalence table (“Myriad”). These models were evaluated using the family data of 307 Dutch MBC probands tested for BRCA1/2, 58 (19%) of whom were carriers. We compared the numbers of observed vs predicted carriers and assessed the Area Under the Receiver Operating Characteristic (ROC) Curve (AUC) for each model. BOADICEA predicted the total number of BRCA1/2 mutation carriers quite accurately (observed/predicted ratio: 0.94). When a cut-off of 10% and 20% prior probability was used, BRCAPRO showed a non-significant better performance (observed/predicted ratio BOADICEA: 0.81, 95% confidence interval [CI]: [0.60-1.09] and 0.79, 95% CI: [0.57-1.09], vs. BRCAPRO: 1.02, 95% CI: [0.75-1.38] and 0.94, 95% CI: [0.68-1.31], respectively). Myriad underestimated the number of carriers in up to 69% of the cases. BRCAPRO showed a non-significant, higher AUC than BOADICEA (0.798 vs 0.776). Myriad showed a significantly lower AUC (0.671). BRCAPRO and BOADICEA can efficiently identify MBC patients as BRCA1/2 mutation carriers. Besides their general applicability, these tools will be of particular value in countries with limited healthcare resources.",
keywords = "BOADICEA, BRCA1, BRCA2, BRCAPRO, male breast cancer, Myriad prevalence table, Gene Frequency, Humans, Genetic Predisposition to Disease/genetics, Male, Ovarian Neoplasms/diagnosis, BRCA2 Protein/genetics, Breast Neoplasms/diagnosis, Breast Neoplasms, Male/diagnosis, Genetic Testing/methods, Female, Heterozygote, ROC Curve, Mutation, BRCA1 Protein/genetics, Cohort Studies",
author = "S. Moghadasi and V. Grundeken and Janssen, {L. A.M.} and Dijkstra, {N. H.} and M. Rodr{\'i}guez-Girondo and {van Zelst-Stams}, {W. A.G.} and Oosterwijk, {J. C.} and Ausems, {M. G.E.M.} and Oldenburg, {R. A.} and Adank, {M. A.} and Blom, {E. W.} and Ruijs, {M. W.G.} and {van Os}, {T. A.M.} and {van Deurzen}, {C. H.M.} and Martens, {J. W.M.} and Schroder, {C. P.} and Wijnen, {J. T.} and Vreeswijk, {M. P.G.} and {van Asperen}, {C. J.}",
note = "Funding Information: the Netherlands Organization for Scientific Research (NWO), Grant/Award number: 017.008.022; Leiden University Medical Centre, Grant/Award number: 30.925; Leids Universiteits Fonds, Grant/Award number: LUF 3274/7-11-13\K LUF 3274/7-11-13\K, NZ; Simonsfonds, Grant/Award number: 1074. Funding Information: We thank Medactie for help with editing of the article. We thank Petra J.M. van Hees for helping develop the database of MBC cases who underwent a BRCA1/2 test and Anne Pagan for drawing part of the pedigrees in BRCAPRO and checking the drawn pedigrees in BOADICEA and BRCAPRO. This work is part of the research programme Mosaic, which is financed by the Netherlands Organization for Scientific Research (NWO) (Grant 017.008.022), the Van de Kampfonds from Leiden University Medical Centre (Grant 30.925), the Leids Universiteits Fonds (Grant LUF 3274/7-11-13\K, NZ) and the Simonsfonds (Grant 1074). Nothing to declare. Funding Information: We thank Medactie for help with editing of the article. We thank Petra J.M. van Hees for helping develop the database of MBC cases who underwent a BRCA1/2 test and Anne Pagan for drawing part of the pedigrees in BRCAPRO and checking the drawn pedigrees in BOADICEA and BRCAPRO. This work is part of the research programme Mosaic, which is financed by the Netherlands Organization for Scientific Research (NWO) (Grant 017.008.022), the Van de Kampfonds from Leiden University Medical Centre (Grant 30.925), the Leids Universiteits Fonds (Grant LUF 3274/7-11-13\K, NZ) and the Simonsfonds (Grant 1074). Publisher Copyright: {\textcopyright} 2017 The Authors. Clinical Genetics published by John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. {\textcopyright} 2017 The Authors. Clinical Genetics published by John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.",
year = "2018",
month = jan,
doi = "10.1111/cge.13065",
language = "English",
volume = "93",
pages = "52--59",
journal = "Clinical Genetics",
issn = "0009-9163",
publisher = "Wiley-Blackwell",
number = "1",
}