A pivotal study on patients’ selection for BRCA1 and BRCA2 mutations by different models in Libyan breast cancer women

Abstract

AbstractIntroductionThe BRCA mutation spectrum of familial breast cancer in Libya remains unknown. Several genetic models developed to predict the probability of BRCA1/2 mutations have not been applied in Libya, where the NCCN criteria are used for highly penetrating breast cancer susceptibility genes. This study aimed to predict BRCA1/2 mutation probability in familial breast cancer and eligibility for genetic testing by using BOADICEA and BRCAPRO models and NCCN criteria.MethodsBRCA1/2 mutations were retrospectively predicted in 62 unrelated women with familial breast cancer between 2018 and 2021. Logistic regression, ROC analysis, and AUC were used to compare NCCN referral criteria with the BRCAPRO and BOADICEA scores.ResultsOf 62 breast cancer patients, 32 (51.6%) (mean age 43.5±8 years) were predicted by both models as BRCA mutation carriers. BRCAPRO predicted BRCA1 and BRCA2 mutations in 27.4% and 41.9% of the women, respectively. BOADICEA predicted 8% for BRCA1 and 29% for BRCA2. At least one NCCN criterion was met by 50/62 women (80.6%). Three criteria were statistically significant predictors in BRCAPRO and BOADICEA: breast cancer at ≤ 50 years with one or more close blood relatives with breast cancer, breast cancer patient with a close relative of male breast cancer, and triple-negative breast cancer. For the three respective criteria, sensitivity was 0.78, 0.89 and 0.75, specificity was 0.33, 0.39 and 0.22, AUC was 0.72, 0.75 and 0.76, PPV was 78%, 27.5% and 33.3, and NPV was 67%, 97% and 95.5.ConclusionsBODICEA and BRCAPRO models are suitable for recommending genetic testing for BRCA gene mutations. The NCCN criteria are too broad.