Abstract
BRCA mutations occur frequently in breast cancer (BC), but their prognostic impact on outcomes of BC has not been determined. We conducted an updated meta-analysis on the association between BRCA mutations and survival in patients with BC. Electronic databases were searched. The primary outcome measure was overall survival (OS), and the secondary outcome measures included breast cancer-specific survival (BCSS) and event-free survival (EFS). Hazard ratios (HR) and 95% confidence interval (CI) were abstracted and pooled with random-effect modeling. Data from 297, 402 patients with BC were pooled from 34 studies. The median prevalence rates of BRCA1 and BRCA2 mutations were 14.5% and 8.3%, respectively. BRCA mutations were associated with worse OS (BRCA1: HR = 1.69, 95% CI, 1.35 to 2.12, p < 0.001; BRCA2: HR = 1.50, 95% CI 1.03 to 2.19, p = 0.034). However, this did not translate into poor BCSS (BRCA1: HR = 1.14, 95% CI, 0.81 to 1.16, p = 0.448; BRCA2: HR = 1.16; 95% CI 0.82 to 1.66, p = 0.401) or EFS (BRCA1: HR = 1.10, 95% CI, 0.86 to 1.41, p = 0.438; BRCA2: HR= 1.09; 95% CI 0.81 to 1.47, p = 0.558). Several studies analyzed BRCA1 and BRCA2 mutations together and found no impact on OS (HR = 1.21; 95% CI, 0.73 to 2.00, p = 0.454) or EFS (HR = 0.94; 95% CI, 0.60 to 1.48, p = 0.787). BRCA1 and BRCA2 mutations were associated with poor OS in patients with BC, but had no significant impact on BCSS or EFS. An improved survival was observed in BC patients who had BRCA1 mutation and treated with endocrinotherapy. The results may have therapeutic and prognostic implications important for BRCA mutation carriers with BC.
Highlights
BRCA1 and BRCA2 are tumor suppressor genes identified in the early 1990s [1,2,3,4].The two genes are locate in chromosome 17q and 13q, respectively, and encode factors that inhibit cell growth
The rate can be as high as one percent in certain populations such as the Northern European Jews [52]
6174∆T specific mutation was seen in 1.5 percent of the northern European Jews, while another mutation 999 del 5 occurs in 0.6 percent of Icelanders [53]
Summary
BRCA1 and BRCA2 are tumor suppressor genes identified in the early 1990s [1,2,3,4].The two genes are locate in chromosome 17q and 13q, respectively, and encode factors that inhibit cell growth. The common germline mutations of BRCA1 are 5382 ins C, 185 del AG, 3819 del 5 and 4153 del A, while the common germline mutations of BRCA2 include 4075 del GT and 5802 del4 [5] Germline mutations of these genes confer an increased lifetime risk for a number of malignant tumors, especially breast cancer and ovarian cancer [6, 7]. Compared to non-carriers, BRCA1-associated breast cancers (BCs) are often high-grade and poorly differentiated infiltrating ductal carcinomas with special immunophenotypic features. These tumors are often triple negative ((estrogen receptor (ER), progesterone receptor (PR), and human epidermalgrowth factor receptor-2 www.impactjournals.com/oncotarget (HER-2)) and express cytokeratins 5/6 (CK5/6), cyclin E and p53 [9,10,11]. Some studies even showed BRCA-mutation carriers had better survival than non-carriers [42,43,44]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
