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

Rust K1, Spiliopoulou P2, Tang CY3, Bell C4, Stirling D5, Phang THF6, Davidson R7, Mackean M1, Nussey F1, Glasspool R2, Reed N2, Sadozye A2, Porteous M5, McGoldrick T8, Ferguson M3, Miedzybrodzka Z4,6, McNeish IA2,9, Gourley C1,10.

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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.