Prognostic Impact of BRCA1 and BRCA2 Mutations on Long-Term Survival Outcomes in Egyptian Female Breast Cancer Patients

SIMPLE SUMMARY: Countries with emerging economies suffer from a high incidence of breast cancer and advanced stage at diagnosis, coupled with limited health and medical care resources. Egypt has witnessed the world’s oldest documented cancer case, more than 3500 years BC, and the Egyptian population shows a high degree of genetic diversity compared to other populations due to its complex and diverse ethnic origins, with high incidence and mortality rates of breast cancer. Though the incidence and profile of BRCA1/2 mutations is population specific, data on population-based clinical outcomes are scarce. In this context, this study is an attempt to elucidate the long-term prognostic implications of BRCA1/2 mutations in Egyptian female breast cancer patients over 24 years. We believe that our findings provide indicators to implement screening strategies as well as optimize treatment options and prophylactic measures for BRCA1/2 carriers that can be applied in the routine clinical practice. ABSTRACT: Evidence on the prognostic relevance of BRCA1/2 mutations on breast cancer survival is still debatable. To address this ambiguity, we sought to elucidate the impact of BRCA1/2 mutation carriership on long-term clinical outcomes for the first time in Egyptian female breast cancer patients. This study comprised 103 Egyptian female breast cancer patients previously tested for BRCA1/2 mutations. Clinicopathological characteristics and long-term follow-up data were retrieved from clinical records until death or loss to follow-up. Overall survival (OS), recurrence-free survival (RFS), disease-free survival (DFS), and metastasis-free survival (MFS) were compared in BRCA1/2 mutation carriers and non-carriers. Pathogenic variants (Class 5 according to ACMG/AMP guidelines) were observed in 29 cases. The profile of the detected variants was previously reported. After median follow-up time of 6.9 years (range, 4.2–24.4 years), BRCA1/2 carriers exhibited significantly worse RFS compared to non-carriers (p = 0.01; HR = 3.00 (95%CI 1.35–6.68)). However, we couldn’t demonstrate statistically significant difference between carriers of pathogenic mutations and non-carriers regarding MFS (p = 0.24; HR = 1.38 (95%CI 0.8–2.4)), DFS (p = 0.11; HR = 1.23 (95%CI 0.74–2.06)), or OS (p = 0.36; HR = 1.23 (95%CI 0.58–2.61)). Though no significant impact was observed in OS, yet BRCA1/2 mutation carriers were at high risk of recurrence, highlighting the importance of adopting BRCA screening strategies and prophylactic measures.