Prevalence of germline BRCA1/2 pathogenic variants in unselected Korean patients with HER2-negative metastatic breast cancer: a nationwide prospective study (KCSG BR19-10)

Abstract

Background: Assessment of germline (g) BRCA1/2 status is recommended for all patients with HER2-negative metastatic breast cancer (MBC) to identify candidates for poly(ADP-ribose) polymerase (PARP) inhibitor therapy, which is not always possible in clinical practice due to limited testing resources. In this study, we investigate the cross-sectional prevalence of gBRCA1/2 pathogenic variant (PV) carriers in unselected Korean patients with HER2-negative MBC.

Methods: Patients diagnosed with HER2-negative metastatic BC receiving palliative systemic treatment were eligible for inclusion in the study. Peripheral blood was prospectively drawn from each patient and gBRCA1/2 status was assessed by next-generation sequencing using an NGeneBio BRCAaccuTest.

Findings: A total of 586 patients were enrolled between October 2019 and March 2022, and the prevalence of gBRCA1/2 PV was analyzed in 570 patients. The median age at enrollment was 54 years (interquartile range, 48-61) and 567 patients were female. Among the 570 patients with gBRCA1/2 analysis, 481 had hormone receptor-positive/HER2-negative breast cancer (BC) and 89 had triple-negative breast cancer (TNBC). The overall prevalence of gBRCA1/2 PV carriers was 7.4% (42/570, 95% confidence interval (CI) 5.4%-9.8%) in unselected patients with HER2-negative MBC [gBRCA1, 1.8% (95% CI 0.8%-3.2%), 10/570; gBRCA2, 5.6%(95% CI % - 7.8%), 32/570]. The overall prevalence of gBRCA1/2 PV carriers in Korean patients with HER2-negative MBC and a low risk of hereditary breast ovarian cancer syndrome (HBOC) was 5.7% [19/332, 95% confidence interval 3.5%-8.8%; TNBC 10.5% (95% CI 1.3%-33.1%), 2/19; HR-positive/HER2-negative 5.4%(95% CI 3.2%-8.6%), 17/313].

Interpretation: Our study measured the size of the current underestimation of gBRCA1/2 PV carriers in unselected Korean patients with HER2-negative MBC, particularly in patients without high risk factors for HBOC. An active screening strategy for unselected HER2-negative MBC should be pursued to avoid missing potential candidates for systemic treatment with PARP inhibitors.

Funding: Pfizer.