New paradigms for<i>BRCA1</i>/<i>BRCA2</i>testing in women with ovarian cancer: results of the Genetic Testing in Epithelial Ovarian Cancer (GTEOC) study

Plaskocinska, Inga; Shipman, Hannah; Drummond, James; Thompson, Edward H.; Buchanan, Vanessa; Newcombe, Barbara; Hodgkin, Charlotte; Barter, Elisa; Ridley, Paul; Ng, Ray Kit; Miller, Suzanne; Dann, Adela; Licence, Victoria; Webb, Hayley; Tan, Li Tee; Daly, Margaret; Ayers, S.; Rufford, Barnaby; Earl, Helena; Parkinson, Christine; Duncan, Timothy J.; Jimenez-Liñan, Mercedes; Sagoo, Gurdeep S.; Abbs, Stephen; Hulbert‐Williams, Nicholas J.; Pharoah, Paul D.P.; Crawford, Robin; Brenton, James D.; Tischkowitz, Marc

doi:10.1136/jmedgenet-2016-103902

Cited by 58 publications

(88 citation statements)

References 27 publications

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“…The oldest mutation carrier identified was 84 years old. Our data contrast with a recent study from the east of England, where only one of 86 women over the age of 70 years carried a pathogenic mutation, which led the authors to conclude that testing should be restricted to patients under 70 years of age in the absence of positive family history. Our results are more in line with those of Norquist et al, who identified BRCA1/2 mutations in over 5% of their population aged 70–79 years .…”

Section: Discussioncontrasting

confidence: 99%

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

Rust

Spiliopoulou

Tang

et al. 2018

BJOG

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Objective To determine the rates of germline BRCA1 and BRCA2 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 BRCA1 and BRCA2 (gBRCA1/2) 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 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. A total of 48% (15/31) ‘new criteria’ patients with gBRCA1/2 mutations had a Manchester score of <15 and would not have been offered sequencing based on family history criteria. In addition, 20 patients with gBRCA1/2 were identified in the prevalent population. The prevalence of gBRCA1/2 mutations in patients aged >70 years was 8.2%. Conclusions Sequencing all patients with non‐mucinous ovarian cancer gives a much higher annual gBRCA1/2 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.

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Section: Discussioncontrasting

confidence: 99%

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

Rust

Spiliopoulou

Tang

et al. 2018

BJOG

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“…There was a good validation of the new MSS (MSS3) in a population-based cohort of epithelial ovarian cancer22 with 15/17 (88.2%) being detected at the 10% (15-point) threshold.…”

Section: Discussionmentioning

confidence: 97%

Pathology update to the Manchester Scoring System based on testing in over 4000 families

et al. 2017

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“…In an East of England series (GTEOC study), the prevalence of germline pathogenic BRCA1/2 variants among all high-grade serous and endometrioid ovarian cancer cases was 8% (18/232) and increased to 12% (17/146) in women diagnosed under the age of 70 years, but fell to 1% (1/86) in those aged ≥70 years 19. Similarly, in a Scottish series, the prevalence of pathogenic BRCA1/2 variants among unselected non-mucinous epithelial ovarian cancer was 13.1% (31/236), but fell to 8.2% (13/159) in women diagnosed over the age of >70 years 20.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of germline pathogenic BRCA1/2 variants in sequential epithelial ovarian cancer cases

et al. 2019

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IntroductionPoly(ADP-ribose) polymerase inhibitors significantly improve progression-free survival in platinum-sensitive high-grade serous and endometrioid ovarian carcinoma, with greatest benefits observed in women with a pathogenic BRCA1/2 variant. Consequently, the demand for germline BRCA1/2 testing in ovarian cancer has increased substantially, leading to the screening of unselected populations of patients. We aimed to determine the prevalence of pathogenic germline BRCA1/2 variants in women diagnosed with epithelial ovarian cancer, categorised according to the established risk factors for hereditary breast and ovarian cancer syndrome and the Manchester BRCA Score, to inform risk stratification.MethodsA cohort of sequential epithelial ovarian cancer cases recruited between June 2013 and September 2018 underwent germline BRCA1/2 testing by next-generation sequencing and multiplex ligation-dependent probe amplification.ResultsFive hundred and fifty-seven patients were screened. Of these, 18% had inherited a pathogenic BRCA1/2 variant. The prevalence of pathogenic BRCA1/2 variants was >10% in women diagnosed with ovarian cancer earlier than 60 years of age (21%) and those diagnosed later than 60 years of age with a family history of breast and/or ovarian cancer (17%) or a medical history of breast cancer (34%). The prevalence of pathogenic BRCA1/2 variants was also >10% in women with a Manchester BRCA Score of ≥15 points (14%).DiscussionOur study suggests that age at diagnosis, family history of breast and/or ovarian cancer, medical history of breast cancer or a Manchester BRCA Score of ≥15 points are associated with a >10% prevalence of germline pathogenic BRCA1/2 variants in epithelial ovarian cancer.

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New paradigms forBRCA1/BRCA2testing in women with ovarian cancer: results of the Genetic Testing in Epithelial Ovarian Cancer (GTEOC) study

Cited by 58 publications

References 27 publications

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

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

Pathology update to the Manchester Scoring System based on testing in over 4000 families

Prevalence of germline pathogenic BRCA1/2 variants in sequential epithelial ovarian cancer cases

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