Routine germline BRCA1 and BRCA2 testing in ovarian carcinoma patients: analysis of the Scottish real life experience

Objective: To determine the rate of germline BRCA1 and BRCA2 mutations in Scottish ovarian cancer patients before and after a change in testing policy. Design: Retrospective cohort study. Setting: Four cancer/genetics centres in Scotland. Population: Ovarian cancer patients undergoing germline BRCA1 and BRCA2 (gBRCA1/2) gene sequencing before 2013 (‘old criteria’; selection based solely on family history), after 2013 (‘new criteria’; sequencing offered to newly presenting non-mucinous ovarian cancer patients) and the ‘prevalent population’ (who presented before 2013, were not eligible for sequencing under the old criteria but were sequenced under the new criteria). Methods: Clinicopathological and sequence data were collected before and for 18 months after this change in selection criteria. Main Outcome Measures: Frequency of germline BRCA1, BRCA2, RAD51C and RAD51D mutations. Results: Of 599 patients sequenced, 205, 236 and 158 were in the ‘old criteria’, ‘new criteria’ and ‘prevalent’ populations respectively. The frequency of gBRCA1/2 mutations was 30.7%, 13.1% and 12.7% respectively. The annual rate of gBRCA1/2 mutation detection was 4.2 before and 20.7 after the policy change. 48% (15/31) ‘new criteria’ patients with gBRCA1/2 mutations had a Manchester score 70 years was 8.2%. Conclusions Sequencing all non-mucinous ovarian cancer patients produces much higher annual gBRCA1/2 mutation detection with the frequency of positive tests still exceeding the 10% threshold upon which many family history based models operate.