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

Evans, D. Gareth; Harkness, Elaine F.; Plaskocinska, Inga; Wallace, Andrew; Clancy, Tara; Woodward, Emma R; Howell, Anthony; Tischkowitz, Marc; Lalloo, Fiona

doi:10.1136/jmedgenet-2017-104584

Cited by 57 publications

(65 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In our study, across the North West of England, selection criterion for germline BRCA1/2 testing was mostly based on an individual’s pathology adjusted Manchester Score of ≥15 points, with 17% (94/557) falling below the 15-point threshold 30. This scoring system provides an alternative method for determining whether an individual’s combined BRCA1 and BRCA2 carrier probability is ≥10% (table 1).…”

Section: Discussionmentioning

confidence: 99%

“…30 The development of the Manchester Scoring System was based on empirical data gathered from the Manchester mutation-screening programme 31. Each individual, from one side of the family, is scored for each gene separately, BRCA1 and BRCA2 (table 1).…”

Section: Methodsmentioning

confidence: 99%

“…Each individual, from one side of the family, is scored for each gene separately, BRCA1 and BRCA2 (table 1). For index cases of breast cancer or any index case or unaffected relative of an index case of ovarian cancer (<60 years), the BRCA1 and BRCA2 scores are adjusted according to pathology 30. The pathology adjustment takes into account the higher prevalence of germline pathogenic BRCA1/2 variants in triple-negative breast cancer and high-grade serous ovarian carcinoma 32.…”

Section: Methodsmentioning

confidence: 99%

“…Each individual and family characteristic (from one side of the family only) is given a numerical weight and these are added to give a score for each of the two genes, BRCA1 and BRCA2 30. Score ‘Cancer, age at diagnosis’ first and then adjust score based on ‘Pathology adjustment’.…”

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

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

et al. 2019

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…The recent iteration in 2017 (MSS3), involved four major updates. The changes included adding scores for adopted patients (ie, family history unknown), increasing the downward adjustment for HER2 receptor status and increasing the weightage for TNBC and high-grade serous ovarian cancer (HGSOC) 13. These updates addressed patients with HGSOC, reporting 17.1% incidence of BRCA1/2 mutations 14.…”

Section: Introduction and Aimsmentioning

confidence: 99%