A systematic review of the international prevalence of BRCA mutation in breast cancer

Abstract

A systematic review was conducted, summarizing international BRCA 1 or 2 (BRCA1/2) mutation prevalence in breast cancer. Databases (eg, Medline and Embase; N=7) and conferences were searched (January 2012 to December 2017). From 17,872 records, 70 studies were included. In 58 large (N>100) studies, BRCA1/2 mutation prevalence varied widely from 1.8% (Spain) in sporadic breast cancer to 36.9% (United States) in estrogen receptor/progesterone receptor low+ (1-9% on immunohistochemistry/human epidermal growth factor receptor 2-negative [HER2-]) breast cancer. In 2 large studies unselected for family history, ethnicity, sex, or age and no/unclear selection by breast cancer stage or hormone receptor (HR) status, germline BRCA (gBRCA) mutation prevalence was 2.9% (Italy) to 3.0% (South Korea). In the 4 large unselected triple-negative breast cancer studies, gBRCA mutation prevalence varied from 9.3% (Australia) to 15.4% (United States). gBRCA mutation prevalence in 1 large unselected HR positive/HER2- early breast cancer study was 5% (United States). In 2 large unselected metastatic breast cancer studies, gBRCA mutation prevalence was 2.7% (France) and 4.3% (Germany). Locally advanced breast cancer studies were small and not in unselected populations. Poor reporting of gBRCA status and basis of selection implies a need for further large well-reported BRCA mutation prevalence studies in breast cancer.

Keywords: BRCA1; BRCA2; chemotherapy; prevalence; systematic review.

Figure 1

PRISMA flow chart detailing literature searches and inclusion screening.

Figure 2

Summary of JBI risk of bias assessment for prevalence studies. Abbreviations: JBI, Joanna Briggs Institute.

Figure 3

Prevalence (%) in largest (N>500) studies. Notes: Horizontal axis has 3 levels: bottom – selection (family history/sex/ethnicity); middle – hormone receptor status (red = TNBC, dark green = mixed, light green = NR/unclear); top – country. BC stage not shown because NR/unclear for all but 2 studies (1 mixed and 1 invasive); *Bar for Son, 2012 is striped in order to distinguish it from bar for Kim, 2012: it is of mixed hormone receptor status. Pale blue = germline reported; red text = deleterious/pathogenic/clinically significant reported. High risk: based on fulfilment of at least 1 of a set of criteria, including family history, early onset, or male BC, which vary by study (See Table 1). Mixed: implies that the study included both those individuals with and without a family history of breast cancer, but the study did not report that probands were unselected. Abbreviations: BC, breast cancer; NR, not reported; TNBC, triple-negative breast cancer.