The uptake of predictive DNA testing in 40 families with a pathogenic BRCA1/BRCA2 variant. An evaluation of the proband-mediated procedure

Menko, Fred H.; Jeanson, Kiki N; Bleiker, Eveline M. A.; Tiggelen, Carla W M van; Hogervorst, Frans B.L.; Stege, Jacqueline A. ter; Moha, Daoud Ait; Kolk, Lizet E. van der

doi:10.1038/s41431-020-0618-8

Cited by 24 publications

(27 citation statements)

References 23 publications

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“…Although our study was designed to investigate the overall numbers of CPG-positive index tests and subsequent cascade tests, we did explore the BRCA1 / 2 uptake of cascade testing further as BRCA1/2 counts for >50% of the index and non-index tests in our centre. The only comparable study, albeit much smaller, was in the Dutch population [ 29 ], showing 50% uptake of cascade testing in family members for BRCA1/2. Overall, our at-risk population is much larger, and includes geographically disparate families so that not all cascade testing will be undertaken by our centre.…”

Section: Discussionmentioning

confidence: 99%

30 year experience of index case identification and outcomes of cascade testing in high-risk breast and colorectal cancer predisposition genes

et al. 2021

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It is 30 years since the first diagnostic cancer predisposition gene (CPG) test in the Manchester Centre for Genomic Medicine (MCGM), providing opportunities for cancer prevention, early detection and targeted treatments in index cases and at-risk family members. Here, we present time trends (1990–2020) of identification of index cases with a germline CPG variant and numbers of subsequent cascade tests, for 15 high-risk breast and gastro-intestinal tract cancer-associated CPGs: BRCA1, BRCA2, PALB2, PTEN, TP53, APC, BMPR1a, CDH1, MLH1, MSH2, MSH6, PMS2, SMAD4, STK11 and MUTYH. We recorded 2082 positive index case diagnostic screening tests, generating 3216 positive and 3140 negative family cascade (non-index) tests. This is equivalent to an average of 3.05 subsequent cascade tests per positive diagnostic index test, with 1.54 positive and 1.51 negative non-index tests per family. The CPGs with the highest numbers of non-index positive cases identified on cascade testing were BRCA1/2 (n = 1999) and the mismatch repair CPGs associated with Lynch Syndrome (n = 731). These data are important for service provision and health economic assessment of CPG diagnostic testing, in terms of cancer prevention and early detection strategies, and identifying those likely to benefit from targeted treatment strategies.

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Section: Discussionmentioning

confidence: 99%

30 year experience of index case identification and outcomes of cascade testing in high-risk breast and colorectal cancer predisposition genes

et al. 2021

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“…The response to cascade screening was higher for female than for male index participants, indicating the need for improved communication with gender-specific heritable disorders. 38,39 The contacting of family members for cascade screening is one way to maximize the impact of a population biobank, and further investigation is needed to determine the best way to increase response rates for optimization of this cascade approach.…”

Section: Potential Of Existing Datasetsmentioning

confidence: 99%

Genotype-first approach to the detection of hereditary breast and ovarian cancer risk, and effects of risk disclosure to biobank participants

et al. 2020

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“…The response to cascade screening was higher for female than for male index participants, indicating the need for improved communication with gender-specific heritable disorders. 38,39…”

Section: Discussionmentioning

confidence: 99%

Genotype-first approach to the detection of hereditary breast and ovarian cancer risk, and effects of risk disclosure to biobank participants

Leitsalu

Palover

Sikka

et al. 2020

Preprint

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Genotype-first approach allows to systematically identify carriers of pathogenic variants in BRCA1/2 genes conferring a high risk of familial breast and ovarian cancer. Participants of the Estonian biobank have expressed support for the disclosure of clinically significant findings. With an Estonian biobank cohort, we applied a genotype-first approach, contacted carriers and offered return of results with genetic counseling. We evaluated participants responses to and the clinical utility of the reporting of actionable genetic findings. Twenty-two of 40 contacted carriers of 17 pathogenic BRCA1/2 variants responded and chose to receive results. Eight of these 22 participants qualified for high-risk assessment based on National Comprehensive Cancer Network criteria. Twenty of 21 counseled participants appreciated being contacted. Relatives of 10 participants underwent cascade screening. Five of 16 eligible female BRCA1/2 variant carriers chose to undergo risk-reducing surgery, and 10 adhered to surveillance recommendations over the 30-month follow-up period. We recommend the return of results to population-based biobank participants; this approach could be viewed as a model for population-wide genetic testing. The genotype-first approach permits the identification of individuals at high risk who would not be identified by application of an approach based on personal and family histories only.

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The uptake of predictive DNA testing in 40 families with a pathogenic BRCA1/BRCA2 variant. An evaluation of the proband-mediated procedure

Cited by 24 publications

References 23 publications

30 year experience of index case identification and outcomes of cascade testing in high-risk breast and colorectal cancer predisposition genes

30 year experience of index case identification and outcomes of cascade testing in high-risk breast and colorectal cancer predisposition genes

Genotype-first approach to the detection of hereditary breast and ovarian cancer risk, and effects of risk disclosure to biobank participants

Genotype-first approach to the detection of hereditary breast and ovarian cancer risk, and effects of risk disclosure to biobank participants

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