A new scoring system in cancer genetics: application to criteria for<i>BRCA1</i>and<i>BRCA2</i>mutation screening

Bonaı̈ti, B.; Alarcon, Flora; Andrieu, Nadine; Bonadona, Valérie; Dondon, Marie-Gabrielle; Pennec, Sophie; Stoppa‐Lyonnet, Dominique; Bonaïti‐Pellié, Catherine; Perdry, Hervé

doi:10.1136/jmedgenet-2013-101674

Cited by 5 publications

(10 citation statements)

References 32 publications

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“…The performance of the new scoring system was evaluated using a simulation of 10 million families, built from women affected with breast or ovarian cancer at different ages. 76, 79 At a score threshold of 5, where positive predicted value (PPV) (15% ie, percentage of carriers among tested individuals) and specificity (87% ie, percentage of non-tested individuals among non-carriers) are similar to the Manchester scoring system with a pathogenic mutation probability of 10%, sensitivity (ie, percentage of tested individuals among carriers) with the new scoring system was higher than the Manchester scoring system (77 vs 72%). 76 The improved performance of the new scoring system compared with the Manchester scoring system was attributed to accounting for unaffected family members and for the degree of kinship of relatives with the proband.…”

Section: Pathogenic Brca Mutation Testing For Cancer Preventionmentioning

confidence: 95%

“…Scoring systems avoid data entry, are a good proxy to probability computations and can generally be easily modified to include new relevant predictive factors. 76 …”

Section: Pathogenic Brca Mutation Testing For Cancer Preventionmentioning

confidence: 99%

“…76 The new scoring system is based on the conditional probability P that a proband is a carrier, given all relevant predictive information in the family. Parameters taken into account include pathogenic BRCA1/2 mutation frequencies in the population, as well as breast and ovarian cancer risks in carriers and non-carriers.…”

Section: Pathogenic Brca Mutation Testing For Cancer Preventionmentioning

confidence: 99%

“…Despite mutation detection threshold (PPV) lowering, 76 there remains a need to broaden BRCA1/2 testing criteria in order to optimise use of BRCA testing to guide treatment decisions. One approach to broadening BRCA1/2 testing criteria is by introducing individual criteria, such as including women with triple-negative (TN) breast cancer (ie, negative for oestrogen receptor, progesterone receptor expression and HER2 amplification) and women with high-grade ovarian cystoadenocarcinoma.…”

Section: Pathogenic Brca Mutation Testing For Cancer Treatmentmentioning

confidence: 99%

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The biological effects and clinical implications of BRCA mutations: where do we go from here?

Stoppa‐Lyonnet

2016

Eur J Hum Genet

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BRCA1 and BRCA2 are tumour-suppressor genes encoding proteins that are essential for the repair of DNA double-strand breaks by homologous recombination (HR). Cells that lack either BRCA1 or BRCA2 repair these lesions by alternative, more error-prone mechanisms. Individuals carrying germline pathogenic mutations in BRCA1 or BRCA2 are at highly elevated risk of developing breast and/or ovarian cancer. Genetic testing for germline pathogenic mutations in BRCA1 and BRCA2 has proved to be a valuable tool for determining eligibility for cancer screening and prevention programmes. In view of increasing evidence that the HR DNA repair pathway can also be disrupted by sequence variants in other genes, screening for other BRCA-like defects has potential implications for patient care. Additionally, there is a growing argument for directly testing tumours for pathogenic mutations in BRCA1, BRCA2 and other genes involved in HR-DNA repair as inactivation of these genes may be strictly somatic. Tumours in which HR-DNA repair is altered are most likely to respond to emerging targeted therapies, such as inhibitors of poly-ADP ribose polymerase. This review highlights the biological role of pathogenic BRCA mutations and other associated defects in DNA damage repair mechanisms in breast and ovarian cancer, with particular focus on implications for patient management strategies.

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Section: Pathogenic Brca Mutation Testing For Cancer Preventionmentioning

confidence: 95%

“…Scoring systems avoid data entry, are a good proxy to probability computations and can generally be easily modified to include new relevant predictive factors. 76 …”

Section: Pathogenic Brca Mutation Testing For Cancer Preventionmentioning

confidence: 99%

Section: Pathogenic Brca Mutation Testing For Cancer Preventionmentioning

confidence: 99%

Section: Pathogenic Brca Mutation Testing For Cancer Treatmentmentioning

confidence: 99%

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The biological effects and clinical implications of BRCA mutations: where do we go from here?

Stoppa‐Lyonnet

2016

Eur J Hum Genet

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“…19 The study was approved by the local Ethics Committee in Institut Curie and Grand Ouest Hospitals. Patients gave their informed consent for genetic testing.…”

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confidence: 99%

Breast and ovarian cancer predisposition due to de novo BRCA1 and BRCA2 mutations

et al. 2015

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BRCA1 and BRCA2 are the two major genes predisposing to breast and ovarian cancer. Whereas high de novo mutation rates have been demonstrated for several genes, only 11 cases of de novo BRCA1/2 mutations have been reported to date and the BRCA1/2 de novo mutation rate remains unknown. The present study was designed to fill this gap based on a series of 12 805 consecutive unrelated patients diagnosed with breast and/or ovarian cancer who met the inclusion criteria for BRCA1/2 gene analysis according to French guidelines. BRCA1/2 mutations were detected in 1527 (12%) patients, and three BRCA1 mutations and one BRCA2 mutation were de novo. The BRCA1/2 de novo mutation rate was estimated to be 0.3% (0.1%; 0.7%). Although rare, it may be useful to take the possibility of de novo BRCA1/2 mutation into account in genetic counseling of relatives and to improve the understanding of complex family histories of breast and ovarian cancers.

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BRCA1 Reflects Myocardial Adverse Remodeling in Idiopathic Dilated Cardiomyopathy

Nożyński

Konecka-Mrowka

Zakliczyńśki³

et al. 2016

Transplantation Proceedings

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A new scoring system in cancer genetics: application to criteria forBRCA1andBRCA2mutation screening

Abstract: The new scoring system has a theoretical basis and may be applied to any cancer family syndrome and, more generally, to any disease with monogenic subentities, in which the causal gene mutations have been identified. It will be easily modified when additional predictive factors are found.

Cited by 5 publications

References 32 publications

The biological effects and clinical implications of BRCA mutations: where do we go from here?

The biological effects and clinical implications of BRCA mutations: where do we go from here?

Breast and ovarian cancer predisposition due to de novo BRCA1 and BRCA2 mutations

BRCA1 Reflects Myocardial Adverse Remodeling in Idiopathic Dilated Cardiomyopathy

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