Abstract
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. This article is protected by copyright. All rights reserved.
| Original language | English |
|---|---|
| Pages (from-to) | 1451-1458 |
| Number of pages | 8 |
| Journal | BJOG-An International Journal of Obstetrics and Gynaecology |
| Volume | 125 |
| Issue number | 11 |
| Early online date | 10 May 2018 |
| DOIs | |
| Publication status | Published - Oct 2018 |
Bibliographical note
Funding InformationEdinburgh Ovarian Cancer Database
Cancer Research UK
Keywords
- Journal Article
- BRCA1
- BRCA2
- RAD51C
- RAD51D
- ovarian cancer
Access to Document
- Accepted Manuscript
This is the peer reviewed version of the following article:Rust K, Spiliopoulou P, Tang CY, Bell C, Stirling D, Phang THF, Davidson R, Mackean M, Nussey F, Glasspool RM, Reed NS, Sadozye A, Porteous M, McGoldrick T, Ferguson M, Miedzybrodzka Z, McNeish IA, Gourley C. Routine germline BRCA1 and BRCA2 testing in patients with ovarian carcinoma: analysis of the Scottish real‐life experience. BJOG 2018; 125:1451–1458., which has been published in final form at DOI: 10.1111/1471-0528.15171. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.