Abstract P1-08-10: Clinicopathological characteristics and clinical outcome in Egyptian female breast cancer patients with and without BRCA1/2 mutations
Authors: AbdelHamid SG , El-Mesallamy HO , AbdelAziz HM , Zekri A-RN 
Published: May 2016

Abstract
Background: Germline mutations in BRCA1 and BRCA2 genes confer high risk of developing breast cancer. We sought to examine for the first time in the Egyptian population, which has witnessed the world's oldest recorded breast cancer case, 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 diagnosed with breast cancer before 2008 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 between BRCA mutation carriers and non-carriers, respectively, using Chi-square. Disease free survival (DFS) was estimated by Kaplan–Meier method and compared in the two groups with log-rank. Survival Cox proportional hazards models were fit to determine the independent association of mutation status with outcome.
Results: The overall rate of BRCA1/2 mutations was 44% (46/103). 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). Grade and histology were not associated with mutation status. 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). Multivariate logistic regression model showed that early age at onset, positive lymph node involvement, family history of any cancer (P=0.047, 0.05 and 0.05, respectively) are independent predictive factors for occurrence of BRCA1/2 mutations. Carriers of BRCA2 deleterious mutations were more likely to report positive family history of cancer other than breast compared to non-carriers (P=0.001). The median follow-up time for the cohort was 5.53 years (ranged from 4.7 to 20.4 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 is the first study in the Middle East to show that BRCA-related breast cancers in the Egyptian population have distinctive clinical and tumor features as well as outcome. Early onset breast cancer, family history of cancer and positive lymph node involvement are predictors for BRCA mutation in this Egyptian cohort. This data has important health implications for guiding cancer control policies.
Citation Format: AbdelHamid SG, El-Mesallamy HO, AbdelAziz HM, Zekri A-RN. Clinicopathological characteristics and clinical outcome in Egyptian female breast cancer patients with and without BRCA1/2 mutations. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-08-10.