Routine germline BRCA 1 BRCA BRCA 1 and BRCA 2 BRCA BRCA 2 testing in patients with ovarian carcinoma: analysis of the Scottish real‐life experience

摘要

Objective To determine the rates of germline BRCA 1 and BRCA 2 mutations in Scottish patients with ovarian cancer, before and after a change in testing policy. Design Retrospective cohort study. Setting Four cancer/genetics centres in Scotland. Population Patients with ovarian cancer undergoing germline BRCA 1 and BRCA 2 ( gBRCA 1/2 ) sequencing before 2013 (under the ‘old criteria’, with selection based solely on family history), after 2013 (under the ‘new criteria’, with sequencing offered to newly presenting patients with non‐mucinous ovarian cancer), and in the ‘prevalent population’ (who presented before 2013, but 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 BRCA 1 , BRCA 2 , RAD 51C , and RAD 51D mutations. Results Of 599 patients sequenced, 205, 236, and 158 were in the ‘old criteria’, ‘new criteria’, and ‘prevalent’ populations, respectively. The frequency of gBRCA 1/2 mutations was 30.7, 13.1, and 12.7%, respectively. The annual rate of gBRCA 1/2 mutation detection was 4.2 before and 20.7 after the policy change. A total of 48% (15/31) ‘new criteria’ patients with gBRCA 1/2 mutations had a Manchester score of 15 and would not have been offered sequencing based on family history criteria. In addition, 20 patients with gBRCA 1/2 were identified in the prevalent population. The prevalence of gBRCA 1/2 mutations in patients aged 70 years was 8.2%. Conclusions Sequencing all patients with non‐mucinous ovarian cancer gives a much higher annual gBRCA 1/2 mutation detection rate, with the frequency of positive tests still exceeding the 10% threshold upon which many family history‐based models operate. Tweetable abstract BRCA sequencing all non‐mucinous cancer patients increases mutation detection five fold.