Comparison of Clinical Outcomes of BRCA1/2 Pathologic Mutation, Variants of Unknown Significance, or Wild Type Epithelial Ovarian Cancer Patients

Abstract

Purpose: The purpose of this study was to investigate the clinical features of epithelial ovarian cancer (EOC) patients according to BRCA1/2 mutation status (mutation, variant of uncertain significance [VUS], or wild type).

Materials and methods: We analyzed 116 patients whose BRCA1/2 genetic test results were available for mutation type and clinical features, including progression-free survival (PFS), overall survival (OS), and response rate. These characteristics were compared according to BRCA1/2 mutation status.

Results: Thirty-seven (37/116, 31.9%) BRCA1/2mutations were identified (BRCA1, 30; BRCA2, 7). Mutation of c.3627_3628insA (p.Leu1209_Glu1210?fs) in BRCA1 was observed in five patients (5/37, 13.5%). Twenty-five patients had BRCA1/2 VUSs (25/116, 21.6%). Personal histories of breast cancer were observed in 48.6% of patients with BRCA1/2 mutation (18/37), 16.0% of patients with BRCA1/2 VUS (4/25), and 7.4% of patients with BRCA wild type (4/54) (p < 0.001). Patients with BRCA1/2 mutation showed longer OS than those with BRCA1/2 wild type (p=0.005). No significant differences were detected in PFS, OS, or response rates between patients with BRCA1/2 VUS and BRCA1/2 mutation (p=0.772, p=0.459, and p=0.898, respectively).

Conclusion: Patientswith BRCA1/2 mutation had longer OS than thosewith BRCA1/2wild type. Patients with BRCA1/2 mutation and BRCA1/2 VUS displayed similar prognoses.

Keywords: BRCA1; BRCA2; Ovarian epithelial cancer; Prognosis.

Fig. 1.

Patient selection diagram. VUS, variant of uncertain significance.

Fig. 2.

Progression-free survival (PFS) curves according to BRCA1/2 mutation status. Median PFS was 17 months for BRCA1/2 mutation patients, 14 months for BRCA1/2 variant of uncertain significance (VUS) patients, and 13 months for BRCA1/2 wild type patients. A log-rank test revealed longer PFS for BRCA1/2mutation than wild type patients; however, this was not statistically significant (p=0.071). No differences were detected between BRCA1/2 wild type and VUS (p=0.455) or BRCA1/2 mutation and VUS (p=0.772).

Fig. 3.

Overall survival (OS) curves according to BRCA1/2 mutation status. Median OS was 33 months for BRCA1/2 mutation patients, 24 months for BRCA1/2 variant of uncertain significance (VUS) patients, and 17 months for BRCA1/2 wild type patients. A log-rank test revealed significantly longer OS for BRCA1/2mutation than wild type patients (p=0.005). No differences were detected between BRCA1/2 wild type and VUS (p=0.211) or BRCA1/2 mutation and VUS (p=0.459).