An international systematic review (SR) of breast cancer (BC) BRCA mutation (BRCAm) prevalence

Abstract

Background: Carriers of BRCAmhave an increased risk of developing BC. Considering the availability of BRCAm-targeted advanced breast cancer (aBC) drugs and evolving treatment guidelines, an SR was conducted to summarise the prevalence of BRCAm carriers in the overall BC population and stratified by clinical and demographic subgroups in different countries. Methods: This SR adhered to the Cochrane method. Electronic databases (eg, Medline & Embase; n=7) and grey literature sources were searched (Jan 2012 to Nov 2017). Studies reporting on BC BRCAm prevalence were included. BRCA1/2m prevalence (including germline) in BC (overall and aBC), clinical (TNBC, HR+/HER2- BC), and demographic subgroups (race/ethnicity) were summarised. Results: 17,872 records were retrieved; 70 studies were included. Regions/countries: Europe (n=16), USA (n=33), Canada (n=2), Australia (n=2), Japan (n=1), South Korea (n=11), Russia (n=2), and Israel (n=3). Only 29 studies explicitly reported BRCA germline status with prevalence ranging from 1.8%in an overall BC population (Sardinia) to 59.52% in a study of BC with family history (Spain). BRCAm prevalence varied widely in 16 overall BC population studies ranging from 2.7% (France) to 23.6% (Italy). Broader BRCAm prevalence ranges were observed in 5 aBC studies, varying from 2% in an overall BC population (France) to 53.8% in a study of Ashkenazi Jews (Israel). 42 reported BRCA1m and BRCA2m separately with no consistent distribution pattern between the 2. In the 24 TNBC studies, prevalence varied from 9.3% in an overall BC population (Australia) to 73.3% in a study of BC with a family history (Israel). BRCA1m prevalence was higher in TNBC studies that reported BRCA1m separately from BRCA2m (16 of 24 studies). In 3 studies of HR+/HER2- BC, BRCAm prevalence varied from 5% (USA) to 9.9% (South Korea). BRCAmprevalence ranged from 14.2% (USA) to 53.8% (Israel) in those of Ashkenazi Jewish ancestry. Conclusions: Reported BRCAm prevalence in BC varies widely in clinical and demographic subgroups across countries; there are few studies on aBC and most lack germline BRCAm status specification. Further BC BRCAm epidemiologic studies are warranted to validate the prevalence of BRCAm with germline status.