Prediction of BRCA1 and BRCA2 mutations by the BODICEA and BRCAPRO models and NCCN criteria in Libyan breast cancer women

The 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. We 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. BRCA1/2 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. Of 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%). Only two criteria were statistically significant predictors in BRCAPRO and BOADICEA: breast cancer at ≤ 50 years with one or more close blood relatives with breast cancer, and breast cancer patient with a close relative of male breast cancer. For the two respective criteria, sensitivity was 0.78 and 0.89, specificity 0.33 and 0.39, AUC 0.72 and 0.75, PPV 78% and 27.5%, and NPV 67% and 97%. BODICEA and BRCAPRO models are suitable for recommending genetic testing for BRCA gene mutations. The NCCN criteria are too broad. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Research Ethics Committee of National Cancer Institute, Sabratha, Libya, gave ethical approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors