Abstract 428: Long-term survival outcomes in Egyptian female breast cancer patients with and without BRCA mutations
Authors: AbdelHamid Sherihan Galal , El-Mesallamy Hala Osman , AbdelAziz Hany , zekri Abdel-Rahman N. 
Published: July 2021

Abstract
Background: Prognostic impact of BRCA1 and BRCA2 mutations in breast cancer has been a subject of several studies over the past few years, with inconsistent interpretations. In an attempt to address this uncertainty, we aimed to study the association between BRCA1/2 mutation carriership and long-term survival outcomes for the first time in Egyptian female breast cancer patients.
Patients and Methods: BRCA1/2 mutations were identified in 103 Egyptian female breast cancer patients using HRM analysis and direct sequencing. DNA for genotyping was extracted from whole blood samples submitted at recruitment. Clinicopathological data and long-term outcomes including date and site of disease progression, were retrieved from medical records until death or loss to follow-up. Outcome measures including overall survival (OS), disease-free survival (DFS), locoregional recurrence free survival (LRRFS) and metastasis free survival (MFS) were compared in all BRCA1 or BRCA2 mutation carriers versus non-carriers at 2, 5, 10, and 15 years after diagnosis.
Results: Pathogenic variants (Class 5 according to American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines) were observed in 29 cases. The profile of the detected variants was previously reported. Median ages at diagnosis was 40 years (range, 24-57 years) in BRCA carriers and 48 years (range, 39-66 years) in non-carriers (P=0.008). BRCA carriers tended to have early onset breast cancer (48% versus 28%, P=0.05), more likely premenopausal (82% vs 54%, P=0.02), and with positive family history of breast cancer (45% vs 35%, P=0.024). Positive lymph node metastasis was more significantly observed in BRCA carriers (76% vs 53%, P=0.03). After median follow-up time of 6.9 years (range, 4.2-24.4 years), there was no significant difference in OS between BRCA carriers and non-carriers at 10 years: 71.1% [95%CI 51-84] vs 94.3% [84-98]; and at 15 years: 60.2% [38-77] vs 60.4% [43-74]; (P=0.36). No difference was detected in DFS between BRCA carriers versus non-carriers (DFS at 2 years: 83% [95%CI 65-92] vs 88% [76-93]; at 5 years: 34% [18-51] vs 61% [47-72]; and at 10 years: 16% [6-35] vs 35% [21-45]); (P=0.1); or MFS (at 2 years were: 83% [95%CI 65-92] vs 87.7% [76-93]; at 5 years: 38.3% [21-56] vs 62.7% [49-73]; and at 10 years: 17.9% [5-35] vs 38.4% [24-52]; (P=0.2). However, LRRFS was significantly worse in BRCA carriers as compared to non-carriers; at 5 years: 51.1% [28-69] vs 84% [70-92]; and at 10 years: 34.1% [10-40] vs 60.1% [50-75]; (P=0.018).
Conclusion: To our knowledge, this is the first study in the Middle East to report the long-term prognostic implications of BRCA1/2 mutations in breast cancer. Though no significant difference was detected in the OS, yet BRCA carriers had high risk of locoregional recurrence and hence, BRCA screening and intensive surveillance should be implemented in the mainstream oncology practice in Egypt.
Citation Format: Sherihan Galal AbdelHamid, Hala Osman El-Mesallamy, Hany AbdelAziz, Abdel-Rahman N. zekri. Long-term survival outcomes in Egyptian female breast cancer patients with and without BRCA mutations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 428.