Prevalence of BRCA1 and BRCA2 Mutations in Patients with Primary Ovarian Cancer – Does the German Checklist for Detecting the Risk of Hereditary Breast and Ovarian Cancer Adequately Depict the Need for Consultation?

Abstract

Background BRCA1/2 mutations are the leading cause of hereditary epithelial ovarian cancer (EOC). The German Consortium for Hereditary Breast and Ovarian Cancer has defined inclusion criteria, which are retrievable as a checklist and facilitate genetic counselling/testing for affected persons with a mutation probability of ≥ 10%. Our objective was to evaluate the prevalence of the BRCA1/2 mutation(s) based on the checklist score (CLS). Methods A retrospective data analysis was performed on EOC patients with a primary diagnosis treated between 1/2011 – 5/2019 at the Central Essen Clinics, where a BRCA1/2 genetic analysis result and a CLS was available. Out of 545 cases with a BRCA1/2 result (cohort A), 453 cases additionally had an extended gene panel result (cohort B). Results A BRCA1/2 mutation was identified in 23.3% (127/545) in cohort A, pathogenic mutations in non-BRCA1/2 genes were revealed in a further 6.2% in cohort B. In cohort A, 23.3% (127/545) of patients had a BRCA1 (n = 92) or BRCA2 (n = 35) mutation. Singular EOC (CLS 2) was present in 40.9%. The prevalence for a BRCA1/2 mutation in cohort A was 10.8%, 17.2%, 25.0%, 35.1%, 51.4% and 66.7% for patients with CLS 2, 3, 4, 5, 6 and ≥ 7 respectively. The mutation prevalence in cohort B was 15.9%, 16.4%, 28.2%, 40.4%, 44.8% and 62.5% for patients with CLS 2, 3, 4, 5, 6 and ≥ 7 respectively. Conclusions The BRCA1/2 mutation prevalence in EOC patients positively correlates with a rising checklist score. Already with singular EOC, the prevalence of a BRCA1/2 mutation exceeds the required 10% threshold. Our data support the recommendation of the S3 guidelines Ovarian Cancer of offering genetic testing to all patients with EOC. Optimisation of the checklist with clear identification of the testing indication in this population should therefore be aimed for.

European experts consensus: BRCA/homologous recombination deficiency testing in first-line ovarian cancer

“…Our literature search retrieved studies indicating that heritable mutations in ovarian cancer risk genes are present in 13-28% 13,[45][46][47] of ovarian cancer patients, and that germline genetic testing is recommended for all such patients, ideally with pre-test genetic counselling. It has also been shown that 50% of high-grade serous ovarian cancer are characterised by HRR deficiency.…”

Hereditary Breast and Ovarian Cancer Service in Sparsely Populated Western Pomerania

“…At the University Medicine Greifswald, the institute of human genetics is the first point of contact for those seeking advice. Trained employees operate a service hotline, evaluate the inclusion criteria according to a standardized check list [ 11 , 20 ] and take care of the appointment management. During the first genetic consultation, documented clinical findings are carefully evaluated, and the pedigree over at least three generations is electronically finalized.…”

Comprehensive Germline Genomic Profiling of Patients with Ovarian Cancer: A Cross-Sectional Study

“…Eighty-one percent of mutations were in the BRCA gene alone. 16 Walsh et al showed that in the American population of prospectively selected OC ( n = 360), 24% had germline mutation,18% in BRCA1/2 , and 6% in non-BRCA genes. 5 In the study done at Royal Marsden Hospital, London, where only BRCA1 and BRCA2 were tested, the yield was 16%.…”