Abstract P4-06-11: Is myriad a reliable genetic risk model for prediction BRCA1/2 mutations in Romanian high-risk breast cancer patients?
Authors: Eniu A , Pop L , Stoian A , Dronca E , Matei R , Ligtenberg M , Ouchene H , Onisim A , Rotaru O , Eniu R , Antone N 
Published: February 2018

Abstract
Aim: To assess the predictive efficacies of genetic risk model Myriad for BRCA1/2 mutations in high-risk Romanian breast cancer patients (pts).
Methods: This prospective study evaluated the validity of Myriad risk assessment model for 250 high-risk breast cancer pts tested for BRCA1/2 mutations between 02.2015-12.2016 at IOCN. Inclusion criteria selected pts diagnosed with triple negative breast cancer under the age of 50, or having conventional family history criteria. All pts signed an informed consent. Myriad calculator software was utilized in order to assess the score for all 250 patients. BRCA testing was performed using an AmpliSeq-based sequencing analysis, on the Ion Torrent Personal Genome Machine at RCFG. Pathogenic mutations were validated using Sanger technology. MLPA was performed for all pts.
Results:The mean Myriad scores for all patients was 8.09% (2.2-26.6%) and the mean Myriad score for BRCA1/2 mutated pts was 11.56% (2.2-26.6%). The majority of pts, 166 (66,4%) presented a Myriad score between 2.2-4.8%, out of which 18 pts (40.9%) were BRCA1/2 mutated. Considering a higher score and the presence of deleterious BRCA1/2 mutations, 12 (27.27%) pts presented a score of 10.3-10.4%, 9 (20.45%) pts a score of 21.2-21.9%, and respectively 5 (11.36%)pts had a score of 26.6%. The subgroup analyzes revealed that the prediction of Myriad genetic risk model in high-risk breast cancer pts was statistical significant when the groups present scores between 10.3 and 26.2%. Other subgroup analysis failed to demonstrate statistical significance.
Table 1: Frequency analysis according to Myriad genetic risk model scores and BRCA1/2 mutational status.Myriad genetic risk model scores* (n=250)BRCA 1/2 mutated (n=44)No BRCA1/2 mutation (n= 191)Variants of unknown significance # (n=18)2.2-4.8% (n=166)18(40.9%)136(71.20%)12(66.66%)6.9%-8% (n=8)08(4.18%)010.3-10.4% (n=45)12(27.27%)29(15.18%)4(22.22%)15.9%(n=1)01(0.52%)021.2%-21.9% (n=14)9(20.45%)4(2.09%)1(5.55%)26.6% (n=16)5(11.36%)10(5.23%)1(5.55%)* The risk was calculated using BRCA risk calculator available at http://www.myriadpro.com/brca-risk-calculator/calc.html # Number of VUS results includes 3 pts that presented BRCA mutations positive results.
Table 2: Myriad genetic risk model stratified by 10.3 and 21.2% scores and BRCA test results.Data analyzedBRCA 1/2 mutatedNo BRCA1/2 mutationTotalP valueMyriad score 10.3%1229410.0100Myriad score 21.2%9413 Total213354
Conclusions: The Myriad genetic risk model can be an acceptable risk assessment tool for determining the risk of carrying BRCA mutations in Romanian population if the score is between 10-20%. The inaccuracy in carrier prediction using Myriad model represents a challenge worthy of additional investigation and comparison with other genetic models. Genetic counselors should recognize this limitation when using Myriad model and recommending genetic testing for Romanian high-risk breast cancer pts.ClinicalTrials.gov Identifier: NCT02317120.
Citation Format: Eniu A, Pop L, Stoian A, Dronca E, Matei R, Ligtenberg M, Ouchene H, Onisim A, Rotaru O, Eniu R, Antone N. Is myriad a reliable genetic risk model for prediction BRCA1/2 mutations in Romanian high-risk breast cancer patients? [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-06-11.