Abstract Background: Breast cancer is the most common malignancy in women in Lebanon and Arab countries with 50% of cases below age 50. The incidence of hereditary breast cancer in Lebanese and Arab women is unknown. Methods: 250 Lebanese women with breast cancer, of young age with or without family history, were recruited at the American University of Beirut Medical Center (AUBMC) between 2009 and 2012. Study was approved by IRB. All signed an informed consent. Risk assessment questionnaire, medical chart review, and whole blood were collected. Coding exons and intron-exon boundaries of BRCA1 and BRCA2 were sequenced. Full BRCA gene sequencing was performed at Institut Jean Perrin, France. Study was funded in part by an Ethnic Research Initiative (ERI) grant awarded by GSK. Results: 14 out of the 250 patients (5.6%) had a deleterious BRCA mutation (7 BRCA1, 7 BRCA2) and 31 (12.4%) had a variant of uncertain significance (VUS). Table 1 shows deleterious BRCA mutations based on age group and FH. Deleterious BRCA mutations based on age group and family history TotalAge ≤ 40 (with no FH)Age ≤ 40 (with positive FH)Age 41-50 (with positive FH)Age ≥ 51 (with positive FH)Number of patients25074747527Patients with deleterious mutations (%)14 (5.6%)1 (1.4%)8 (10.8%)4 (5.3%)1 (3.7%)BRCA 170610BRCA 271231 All 7 BRCA1 mutation carriers had a positive family history, were between 32 and 48 years of age, and had Grade 3 IDC with negative ER, PR, HER2 receptors (TNBC). Six BRCA2 mutation carriers had IDC with positive hormone receptors (HR) and 2 had HER2-positive disease. We found 31 VUS. One VUS (BRCA2) was seen in two sisters with breast cancer. One VUS (BRCA2) was seen in 4 patients and another in 2 patients, while 2 VUS (BRCA1) mutations were seen in 2 sets of 2 patients. The significance of these VUS cannot be ascertained at this time. Haplotype analysis is ongoing. Conclusions: This is the first large study of ethnic Lebanese Arab women with breast cancer. The prevalence of BRCA deleterious mutations in women with breast cancer who are considered high risk of carrying a BRCA mutation is 5.6% in our total cohort, while in patients ≤40 with positive FH it is 10.6%. Those numbers are lower than expected from US and European populations. Tumor grade and pathology characteristics in this patient population correlated with that previously documented for BRCA1 (TNBC) and BRCA2 (positive HR) associated breast cancers. Our data supports use of young age together with positive FH should be used to select patients for counseling and BRCA testing in Lebanon and Arab countries with resource-sensitive guidelines. Several VUS were found in patients and sisters with breast cancer. The finding that 94.4% of high risk patients had no deleterious BRCA mutations suggests the need to look for alternate gene mutations and other factors that may contribute to the development of breast cancer in these high risk patients. Conclusions regarding haplotypes and diversity will be reported at the meeting. Citation Format: Nagi El Saghir, Nancy Uhrhammer, Hussein Assi, Katia Khoury, Stephanie Decousous, Yannick Bidet, Sara Jaber, Raghid Charara, Rania Farhat, Ziad Salem, Ali Shamseddine, Arafat Tfayli, Jaber Abbas, Faek Jamali, Muhieddine Seoud, Deborah Armstrong, Yves-Jean Bignon, Nathalie Zgheib. BRCA1 and BRCA2 mutations in ethnic Lebanese Arab high risk women for hereditary breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-03-06.