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

TY - JOUR

T1 - Routine germline BRCA1 and BRCA2 testing in ovarian carcinoma patients

T2 - analysis of the Scottish real life experience

AU - Rust, Kelly

AU - Spiliopoulou, Pavlina

AU - Tang, Chee Yuan

AU - Bell, Christine

AU - Stirling, Diane

AU - Phang, Tze Hui Fifi

AU - Davidson, Rosemarie

AU - Mackean, Melanie

AU - Nussey, Fiona

AU - Glasspool, Ros

AU - Reed, Nick

AU - Sadozye, Azmat

AU - Porteous, Mary

AU - McGoldrick, Trevor

AU - Ferguson, Michelle

AU - Miedzybrodzka, Zofia

AU - McNeish, Iain A.

AU - Gourley, Charlie

N1 - No funding

PY - 2018/10/1

Y1 - 2018/10/1

N2 - 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.

AB - 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.

KW - Journal article

KW - BRCA1

KW - BRCA2

KW - RAD51C

KW - RAD51D

KW - Ovarian cancer

KW - ovarian cancer

KW - BRCA1

KW - BRCA2

U2 - 10.1111/1471-0528.15171

DO - 10.1111/1471-0528.15171

M3 - Article

C2 - 29460478

SN - 1470-0328

VL - 125

SP - 1451

EP - 1458

JO - BJOG: An International Journal of Obstetrics & Gynaecology

JF - BJOG: An International Journal of Obstetrics & Gynaecology

IS - 11

ER -