272PD BRCA1/2 mutation frequency and patterns of treatment response in Asian women with ovarian, primary peritoneal or fallopian tube carcinoma (OPFC): experience from an Asian cancer centre

Abstract

Aim/Background: Patients with germline BRCA1 or BRCA2 mutation related ovarian, primary peritoneal or fallopian tube carcinoma (BMOPFC) have improved prognosis and higher response rates to certain chemotherapy and poly (ADP-ribose) polymerase (PARP) inhibitors. These features are attributed to homologous recombination mediated DNA repair defects (HRD) resulting in impaired ability of tumour cells to repair double strand breaks and cell death. The frequency of BMOPFC in Asian women is unclear. Methods: Data was prospectively collected on Asian patients with OPFCs referred to the cancer genetics clinic at the National University Hospital, Singapore for counselling from 2014-2015. Germline HRD related gene mutations were determined by next generation sequencing and deletion/duplication analysis. Platinum free intervals (PFI), median progression free survival (mPFS) and response rate (RR) to subsequent lines of chemotherapy were assessed. Results: Out of 64 OPFC patients referred for screening, only 54.7% (n = 35) underwent genetic testing. 31.4% (n = 11; Stage 1:2:3:4:N/A = 0:1:5:4:1) of women tested were found to harbour a pathogenic mutation in the DNA repair pathway, of which 54.5% (n = 7/11) harboured a germline mutation in BRCA1 and 27.3% (n = 3/ 11) in BRCA2. Other HRD related mutations observed were RAD51c (n = 1) and BRIP1 (n = 1). Median age at diagnosis was 49 years and 73% reported a family history of breast, ovarian or prostate cancer. All patients were treated with a 1st line platinum doublet (median PFI of 13 mths [range: 5-45 mths]; mPFS = 17.5 mths). At relapse, a median of 2 (range: 1-4) subsequent lines of platinum-based chemotherapy (2nd line RR = 71.4%, mPFS ≥12 mths; 3rd line RR = 50%, mPFS ≥11.5 mths) were prescribed. Conclusions: BRCA1/2 mutations are common in this small series of Asian women with OPFC. High RRs and prolonged PFS after platinum-based chemotherapy are also a feature of Asian BMOPFC. With the advent of PARP inhibitors, germline BRCA1/2 testing should be offered to all Asian women with non-mucinous OPFC.