Patients’ characteristics
Table 1 contains a comparison of the clinical characteristics between the BRCA wild-type genotype group and the BRCA mutation group. Of the 169 patients included, 122 (71.9%) had the wild-type BRCA genotype, and 47 (28.1%) had the BRCA1/2 mutations. There were no significant between-group differences in patient characteristics such as age, CA-125 level, FIGO stage, histologic type, tumor grade, tumor burden, CRS, residual disease, rate of radical surgery, surgical complexity score, chemotherapy regimen, or cycles of NAC.
CRS relative to BRCA1/2 mutation status
CRS 3 patients were 43 (35.2%) and 16 (34.0%) for patients without and with BRCA1/2 mutations, respectively (P = 0.516) (Table 2). Although CRS 3 rates differed between BRCA1 (26.9%), BRCA2 (42.9%) and the wild-type BRCA genotype, these difference did not achieve statistical significance.
Kaplan–Meier curves for OS and PFS stratified by CRS in patients with the BRCA1/2 mutations are shown in Fig. 2. Fifteen (48.4%) in the CRS 1/2 and 8 (50.0%) in the CRS 3 group had recurred by the time of the analysis. Median PFS in the CRS 1/2 group was 21.7 months (95% confidence interval [CI], 16.2 - 33.3) and 22.0 months (95% CI, 14.4 – 29.6) in the CRS 3 group. Four (12.9%) in the CRS1/2 and no patients in the CRS3 group had died by the time of the analysis. Median OS was not reached in both groups. CRS 3 in patients with the BRCA1/2 mutations was not significantly associated with improved PFS (P = 0.949) and OS (P = 0.168). In patients without BRCA mutations, 52 (65.8%) in the CRS 1/2 and 24 (55.8%) in the CRS 3 group had recurred by the time of the analysis. Median PFS in the CRS 1/2 group was 17.2 months (95% CI, 14.7 – 19.7) and 22.4 months (95% CI, 14.5 – 30.3). Eighteen (22.8%) in the CRS 1/2 and 5 (11.6%) patients in the CRS 3 group had died by the time of the analysis. Median OS in the CRS 1/2 group was 96.4 months (95% C], 27.1 – 165.7) and not reached in the CRS 3 group. However, CRS 3 in patients without BRCA mutations was significantly associated with improved PFS (P = 0.030) and OS (P = 0.039) (Fig. 3). The results of the multivariate Cox regression analyses of PFS and OS in all patients are shown in Additional file 1. In terms of recurrence, multivariate analysis showed that BRCA1/2 mutation was a marginally significant prognostic factor (HR, 0.65; 95% CI, 0.40-1.04). Multivariate analysis showed CRS 3 (HR, 0.29; 95% CI, 0.10-0.80) and BRCA1/2 mutation (HR, 0.27; 95% CI, 0.08-0.92) were significantly associated with a longer OS.
We also categorized the patients based on BRCA mutations and CRS (BRCA1/2 mutations with CRS 1/2; the wild-type BRCA genotype with CRS 1/2; BRCA1/2 mutations with CRS 3; and the wild-type BRCA genotype with CRS 3) to evaluate survival according to the relationship of BRCA1/2 mutations in the CRS. Fifteen (48.4%) in BRCA1/2 mutations with CRS1/2, 52 (65.8%) in the wild-type BRCA genotype with CRS1/2, 8 (50%) in BRCA1/2 mutations with CRS3, and 24 (55.8%) in the wild-type BRCA genotype with CRS3 group had recurred by the time of the analysis. Median PFS in 4 groups were 21.7 (95% CI, 16.2-33.3), 17.2 (95% CI, 14.7-19.7), 22.0 (95% CI, 14.4-29.6), and 22.4 (95% CI, 14.5-30.3), respectively. Three (9.7%) in BRCA1/2 mutations with CRS1/2, 18 (22.8%) in the wild-type BRCA genotype with CRS1/2, 0 (0%) in BRCA1/2 mutations with CRS3, and 5 (11.6%) in the wild-type BRCA genotype with CRS3 group had died by the time of the analysis. Median OS in the BRCA1/2 mutations with CRS3 group was 96.4 and other 3 groups were not reached. In patients with CRS 1/2, the carriers of BRCA1/2 mutations had better PFS (P = 0.044) and OS (P = 0.043) than the wild-type BRCA genotype patients. However, in patients with CRS 3, there was no significant difference in PFS (P = 0.863) and OS (P = 0.216) between BRCA1/2 carriers and the wild-type BRCA genotype patients (Fig. 4). In addition, we performed a subset analysis including only in Grade 3 patients excluding the 16 patients with Grade1 or 2. Similar results were obtained for patients with Grade 3 (Additional file 2). In patients with CRS 1/2, the carriers of BRCA1/2 mutations had better PFS (P = 0.015) and OS (P = 0.049) than the wild-type BRCA genotype patients. However, in patients with CRS 3, there was no significant difference in PFS (P = 0.917) and OS (P = 0.389) between BRCA1/2 carriers and the wild-type BRCA genotype patients.