Abstract PS8-31: Patterns, predictors and prevalence of germline BRCA1 and BRCA2 mutations among young patients with breast cancer in Jordan

Abstract

Abstract Introduction: Hereditary causes, mostly related to BRCA1 and BRCA2 mutations, are not uncommon causes for breast cancer. Western studies had shown that such mutations are more prevalent among younger patients. In this study, we evaluate the prevalence of germline mutations in BRCA1 and BRCA2 among breast cancer patients diagnosed at age 40 or younger. Methods: Data on Jordanian breast cancer patients diagnosed at age 40 years or younger was reviewed. Blood samples were obtained for DNA extraction and BRCA sequencing was performed at reference labs. BRCA1 and BRCA2 mutations were classified as pathogenic/likely pathogenic and variant of uncertain significance (VUS). Results: A total of 616 patients aged 40 years or younger were enrolled. Genetic testing and genetic counseling have been completed for all. Majority (n=499, 81.0%) had a family history of breast cancer and 12.6% had triple-negative disease. Among the whole group, 75 (12.2%) were tested positive for pathogenic or likely pathogenic mutations, mostly (66.7%) in BRCA2 and an additional 57 (9.3%) had VUS. In multivariate analysis, triple-negative disease (Odd Ratio [OR]: 5.37; 95% CI: 2.88-10.02, p<0.0001), breast cancer in two or more family members (OR: 4.44; 95% CI: 2.52-7.84, p<0.0001), and a personal history of two or more primary breast cancers (OR: 3.43; 95% CI: 1.62-7.24, p=0.001) were associated with higher BRCA mutation rates (Table). In multivariate analysis, triple-negative disease (Odds Ratio [OR]: 5.37; 95% CI: 2.88-10.02, p<0.0001), breast cancer in two or more family members (OR: 4.44; 95% CI: 2.52-7.84, p<0.0001), and a personal history of two or more primary breast cancer (OR: 3.43; 95% CI: 1.62-7.24, p=0.001), were associated with higher BRCA mutation rates. A spectrum of 39 different mutations, 22 in BRCA2 and 17 in BRCA1 were detected. To our knowledge, three mutations in BRCA2 (c.4222_4223del and c.6193C>T in exon 11 and c.1013del in exon 10) have not been reported previously in any database. Conclusions: Among young Jordanian patients with breast cancer, mutation rates are significantly higher in patients with triple-negative disease, personal history of breast cancer and those with two or more close relatives with breast cancer. Variables TotalPositive MutationsBRCA1BRCA2BRCA1& BRCA2P-ValueAge at diagnosis (years)≤ 35341163450 (14.7%)0.017> 3527591625 (9.1%)One or more close relative with breast cancer at any ageYes30593746 (15.1%)0.029No311151429 (9.3%)One or more close relatives with breast cancer diagnosed at age 50 years or youngerYes15332427 (17.6%)0.017No463222648 (10.4%)Diagnosed at ≤ 60 years with triple negative diseaseYes6916723 (33.3%)<0.001No54794352 (9.5%)Any age with at least 2 breast cancer primariesYes486814 (29.2%)<0.001No568194261 (10.7%)Two or more close relatives with breast cancerYes9752429 (30.0%)<0.001No519202646 (8.9%)All Patients616255075 (12.2%) Citation Format: Hikmat Abdel-Razeq, Lama Abujamous, Mahmoud Abunasser, Sarah Edaily, Rayan Bater. Patterns, predictors and prevalence of germline BRCA1 and BRCA2 mutations among young patients with breast cancer in Jordan [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-31.