Clinicopathological Characteristics and Clinical Outcome in Egyptian Female Breast Cancer Patients With and Without BRCA1/2 Mutations

Abstract

Introduction: Germline mutations in BRCA1 and BRCA2 genes confer high risk of developing breast cancer. We sought to examine whether the clinicopathological characteristics and the clinical outcome differ in patients with and without BRCA mutations. Patients and Methods: A series of 103 Egyptian female patients were recruited from Breast Cancer Unit, Clinical Oncology Department, Ain Shams University, Egypt. The enrolled patients, unselected for age of onset or family history, were tested for BRCA1/2 mutations using HRM analysis and direct sequencing. The clinical and pathological features of the patients were retrospectively assessed and comparisons were made using Chi-square. Disease free survival (DFS) was estimated by Kaplan–Meier method and compared in the two groups with log-rank. Results: The overall rate of BRCA1/2 mutations was 44%. Novel deleterious mutations were detected and submitted to NCBI Clinvar database. Deleterious mutations were identified in 29 cases and unclassified variants in 32 cases, 15 of which had a co-occuring deleterious mutation. Patients with BRCA mutations tended to have early onset breast cancer compared to non-carriers (P=0.002), more often premenopausal (P=0.006), with a familial history of breast cancer as well as other cancers (P=0.005). BRCA-related breast cancers were more likely to have T3-T4 stage than wild type (41% versus 28%, P=0.02), positive lymph node involvement (78 versus 53%, P=0.007) and develop bilateral breast cancers (24% versus 9%, P =0.007). The incidence of ER negative and PR negative tumors was higher in BRCA carriers, but not statistically significant (P=0.17 and 0.15, respectively). No difference in HER-2/neu status was observed (P=0.25). Early age at onset, positive lymph node involvement, family history of any cancer were independent predictive factors for occurrence of BRCA1/2 mutations. The median follow-up time for the cohort was 5.53 years. Patients with BRCA mutations had poorer 5-year DFS compared to non-carriers (47.7% versus 67.4%, P=0.041); but Cox regression analysis failed to demonstrate a significant independent influence of BRCA mutation status on DFS. Conclusion: This study shows that BRCA-related breast cancers in the Egyptian population have distinctive clinical and tumor features as well as outcome. This data has important health implications for guiding cancer control policies.