BRCA1/2 Mutations and Long-Term Clinical Outcomes in Egyptian Breast Cancer Patients

Abstract

Introduction: Clinical findings regarding the impact of BRCA1/2 mutational status on the prognosis of breast cancer patients are still controversial. We aimed to investigate the prognostic relevance of BRCA1/ 2 mutations on recurrence and long-term survival, for the first time, in Egyptian female breast cancer patients. Patients and Methods: The study cohort comprised 103 Egyptian female breast cancer patients previously tested for BRCA1/2 mutations using HRM analysis and direct sequencing. Clinicopathological and long-term clinical follow-up data 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), recurrence-free survival, and metastasis-free survival (MFS) were compared in all BRCA1/ 2 mutation carriers versus non-carriers at 2, 5, 10, and 15 years after diagnosis. Results: The profile of the detected variants was previously reported. The American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guidelines were used to re-classify the variants. The median follow-up time was 6.9 years (range, 4.2-24.4 years). BRCA carriers had significantly worse DFS than non-carriers, at 2 years 86.7% vs 88.2%; at 5 years 38.1% vs 57.8%; and at 10 years 21.6% vs 34.1% ( P=0.024). Negative estrogen receptor (ER) status (HR=2.44, 95%CI=1.33-4.47) and large tumor size (HR=2.19, HR=1.21-3.98) were also significant factors for worse DFS. Recurrence-free survival was significantly worse in BRCA carriers compared to non-carriers, at 5 years: 95.2% vs 98.2%; at 10 years: 54.4% vs 79.8%; and at 15 years 34.6% vs 61.7% ( P=0.005). BRCA carriers showed poorer OS and MFS, though not statistically significant [OS in BRCA carriers and non-carriers at 5 years: 81.6% vs 89.3%; at 10 years: 59.2% vs 60.6%; and at 15 years: 36.3 vs 59.2% ( P=0.42); and MFS at 2 years 86.7% vs 88.1%; at 5 years 44.5% vs 61.1% ; and at 10 years: 25.3% vs 38.2% ( P=0.41)]. Conclusion: To our knowledge, this is the first study in the Middle East to investigate long-term survival outcome of BRCA1/2 related breast cancer. We, herein, underline the necessity of implementing BRCA screening strategies and intensive surveillance in the mainstream oncology practice in Egypt.