Abstract PS8-34: High rates of BRCA1 and BRCA2 germline mutations among Arab patients with triple-negative breast cancer

Abstract

Abstract Background: Patients with triple-negative (TN) disease, which represent 10-15% of all breast cancer cases, is associated with the worst prognosis among all breast cancer subtypes. Because of higher risk for BRCA mutation, patients diagnosed at age ≤60 years with triple-negative disease should undergo genetic testing. Identification of BRCA1 or BRCA2 mutation has clinical impact on breast and ovarian cancer prevention and treatment. Many drugs were recently approved for patients with BRCA mutation carriers. We here investigate the patterns and prevalence of BRCA1 and BRCA2 mutations among Arab patients diagnosed with this breast cancer subtypes and treated at our institution. Patients and Methods: We utilized our database of all breast cancer patients, from Jordan and neighboring Arab countries, tested for BRCA mutations (n=1302) as per the NCCN guidelines. Patients with no expression of estrogen (ER) or progesterone (PR) receptors and negative for HER2 (triple-negative) were enrolled regardless of their age or family history. Following a detailed genetic counselling in a clinic established for this purpose, BRCA testing was then performed at 3 reference labs in UK and USA. BRCA1 and BRCA2 mutations were classified as pathogenic/likely pathogenic and variant of uncertain significance (VUS). Results: During the three-year study period, a total of 171 (13.1%) of all patients in database fulfilled our inclusion criteria. Twenty-two (12.9%) patients were from Palestine, Syria and Iraq. Median age was 41 (range, 19-77) years and all were females. Among this group, a total of 45 (26.3%) were tested positive for BRCA1 (n=32, 18.7%) or BRCA2 (n=13, 7.6%) while 12 (7.0%) others had VUS. Mutations were detected in 26 (31.7%) of 82 patients who were triple-negative and diagnosed at age 40 years or younger. Additionally, 26 (36.6%) of 71 patients with triple-negative disease who had one or more close relatives with breast, pancreatic, or prostate cancer (Gleason score ≥7) had positive BRCA1 or BRCA2 mutation, too. In multivariate analysis, the impact of younger age on mutation rates was considered insignificant (OR: 1.86; 95%CI: 0.89-3.91; p=0.10). However, breast cancer diagnosis at any age with 2 or more close relatives with breast cancer have is associated with a significantly higher BRCA mutation rate (OR: 2.76; 95%CI: 1.13, 6.71; p = 0.03). Conclusions: Arab patients with triple-negative breast cancer subtype have very high BRCA1 or BRCA2 mutation rates. Family history of breast cancer in close relatives further increase this risk. Citation Format: Hikmat Abdel-Razeq, Lama Abujamous, Rayan Bater. High rates of BRCA1 and BRCA2 germline mutations among Arab patients with triple-negative breast cancer [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 PS8-34.