Mainstream genetic testing for high‐grade ovarian, tubal and peritoneal cancers: A tertiary referral centre experience

Abstract

Background Fifteen percent of ovarian, tubal, and peritoneal (OTP) invasive epithelial cancers are linked to an underlying heritable pathogenic variant (PV) in the BRCA1/2 cancer susceptibility genes. Identifying a PV has management implications for an affected individual and relatives. Cancer team‐facilitated genetic testing (mainstreaming) aims to provide equitable systematic access to genetic testing for appropriate patients. Aim To evaluate a multi‐disciplinary team (MDT)‐led mainstream germline genetic testing program for OTP cancer at a tertiary referral centre. Materials and methods We conducted a retrospective review of our MDT‐led mainstream genetic testing program initiated in June 2017. We included all patients diagnosed with OTP cancer registered with the hospital gynaecological oncology MDT from program initiation to December 2020. Patients were considered eligible for testing if they were diagnosed with a high‐grade epithelial OTP AND ≤70 years, OR if >70 with a first/second degree relative with breast and/or ovarian cancer OR Jewish ancestry. Results Of 205 women diagnosed with high‐grade epithelial OTP cancer, 140 were eligible for mainstreaming. Eight‐five percent were mainstreamed, with the gynae‐oncologists facilitating 64.5% of tests. The overall PV detection rate in BRCA1/2 was 10.1% (BRCA1 n = 9, BRCA2 n = 3). The median turnaround time (TAT) was 44.5 days (range 16–118). All women with PV were referred to the Familial Cancer Service for further assessment and five (of six eligible; 83%) were subsequently treated with polyadenosine diphosphate ribose polymerase inhibitors. Cascade testing was undertaken in 75% of families with a mean of three relatives tested per proband. Conclusion Mainstreamed genetic testing is feasible, with an acceptable TAT, ensuring adequate opportunity to inform treatment decisions. Tumour testing and inclusion of moderate‐risk cancer predisposition genes in mainstreaming represent potential pathways that will require further exploration.

Impact of genetic counselling strategy on diagnostic yield and workload for genome sequencing-based tumour diagnostics

“…It would impose too heavy of a burden on genetic counsellors to offer pre-test counselling too all these patients. Currently, mainstreaming of genetic care, in which pretest counselling by nongenetic health care professionals is integrated into routine care, is studied by multiple groups and seems feasible and resource efficient [50][51][52][53][54][55][56][57][58] . Mainstreaming has many advantages, all patients (that consented) can be included and genetic counsellors only get patients referred with a proven PGV.…”