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

Kelly Rust, Pavlina Spiliopoulou, Chee Yuan Tang, Christine Bell, Diane Stirling, Tze Hui Fifi Phang, Rosemarie Davidson, Melanie Mackean, Fiona Nussey, Ros Glasspool, Nick Reed, Azmat Sadozye, Mary Porteous, Trevor McGoldrick, Michelle Ferguson, Zofia Miedzybrodzka, Iain A. McNeish, Charlie Gourley (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    27 Citations (Scopus)
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    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 <15 and would not have been offered sequencing based on family history criteria. In addition, 20 gBRCA1/2 patients were identified in the prevalent population. The prevalence of gBRCA1/2 mutations in patients >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.

    Original languageEnglish
    Pages (from-to)1451-1458
    Number of pages8
    JournalBJOG: An International Journal of Obstetrics & Gynaecology
    Issue number11
    Early online date20 Feb 2018
    Publication statusPublished - 1 Oct 2018


    • Journal article
    • BRCA1
    • BRCA2
    • RAD51C
    • RAD51D
    • Ovarian cancer
    • ovarian cancer
    • BRCA1
    • BRCA2

    ASJC Scopus subject areas

    • Obstetrics and Gynaecology


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