Performance of <i><scp>BRCA1</scp>/</i>2 mutation prediction models in male breast cancer patients

Moghadasi, Setareh; Grundeken, V.; Janssen, Linda A.M.; Dijkstra, Nizet H.; Rodríguez-Girondo, Mar; Zelst-Stams, Wendy A. G. van; Oosterwijk, Jan C.; Ausems, Margreet G. E. M.; Oldenburg, Rogier A.; Adank, Muriel A.; Blom, Eveline W; Ruijs, Mariëlle; Os, Theo A.M. van; Deurzen, Carolien H.M. van; Martens, John W.M.; Schroder, C.; Wijnen, Juul T.; Vreeswijk, Maaike P.G.; Asperen, Christi J. van

doi:10.1111/cge.13065

Cited by 6 publications

(2 citation statements)

References 41 publications

(77 reference statements)

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“…Also, information about risk-reducing surgery in family members may not necessarily be available in the clinic. Due to few cases, the present study did not evaluate male breast cancer separately, but a validation study focused on this group of patients has previously demonstrated acceptable performance of the model for BRCA1 and BRCA2 37 . Multifactorial risk factors and polygenic risk scores were not included in the present validation but could potentially improve the performance of the model.…”

Section: Discussionmentioning

confidence: 99%

Validation of the BOADICEA model for predicting the likelihood of carrying pathogenic variants in eight breast and ovarian cancer susceptibility genes

Møller

Boonen

Feldner

et al. 2023

Sci Rep

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BOADICEA is a comprehensive risk prediction model for breast and/or ovarian cancer (BC/OC) and for carrying pathogenic variants (PVs) in cancer susceptibility genes. In addition to BRCA1 and BRCA2, BOADICEA version 6 includes PALB2, CHEK2, ATM, BARD1, RAD51C and RAD51D. To validate its predictions for these genes, we conducted a retrospective study including 2033 individuals counselled at clinical genetics departments in Denmark. All counselees underwent comprehensive genetic testing by next generation sequencing on suspicion of hereditary susceptibility to BC/OC. Likelihoods of PVs were predicted from information about diagnosis, family history and tumour pathology. Calibration was examined using the observed-to-expected ratio (O/E) and discrimination using the area under the receiver operating characteristics curve (AUC). The O/E was 1.11 (95% CI 0.97–1.26) for all genes combined. At sub-categories of predicted likelihood, the model performed well with limited misestimation at the extremes of predicted likelihood. Discrimination was acceptable with an AUC of 0.70 (95% CI 0.66–0.74), although discrimination was better for BRCA1 and BRCA2 than for the other genes in the model. This suggests that BOADICEA remains a valid decision-making aid for determining which individuals to offer comprehensive genetic testing for hereditary susceptibility to BC/OC despite suboptimal calibration for individual genes in this population.

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Section: Discussionmentioning

confidence: 99%

Validation of the BOADICEA model for predicting the likelihood of carrying pathogenic variants in eight breast and ovarian cancer susceptibility genes

Møller

Boonen

Feldner

et al. 2023

Sci Rep

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“…BRCAPRO is a validated tool (32) commonly used by genetic counselors to assess a proband's carrier probability to inform mutation testing decision-making (see Supplementary Methods). BRCAPRO uses a variety of information from probands and the entire reported family history (33,34); its calibration has been widely studied in various populations and types of probands (35)(36)(37)(38). BRCAPRO is similar to the BOADICEA (39) model.…”

Section: Calculating Carrier Probability With Brcapromentioning

confidence: 99%

A Pragmatic Testing-Eligibility Framework for Population Mutation Screening: The Example of BRCA1/2

Best

Tucker

Frone

et al. 2019

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Eligibility guidelines for genetic testing may be revisited, given technological advances, plummeting costs, and proposals for population mutation screening. A key property of eligibility criteria is the tradeoff between the number of mutation carriers identified versus population members tested. We assess the fractions of mutation carriers identified, versus women undergoing mutation testing, for BRCA1/2 founder mutation screening in U.S. Ashkenazi-Jewish women.Methods: BRCA1/2 carrier probabilities, based on personal/ family history, were calculated using the risk-prediction tool BRCAPRO for 4,589 volunteers (102 mutation carriers) in the population-based Washington Ashkenazi Study. For each carrier-probability threshold between 0% and 10%, we compared the percentage of founder mutations detected versus the percentage of women requiring mutation testing. PCR mutation testing was conducted at the NIH for the 3 Ashkenazi-Jewish founder mutations (5382insC and 185delAG in BRCA1, and 6174delT in BRCA2).Results: Identifying 90% of BRCA1/2 founder mutations required testing the 60% of Ashkenazi-Jewish women with carrier probabilities exceeding 0.56%, potentially avoiding mutation testing for approximately 0.7 to 1.1 million U.S. Ashkenazi-Jewish women. Alternatively, testing the 44% whose carrier probability exceeded 0.78% identified 80% of mutation carriers, increasing to 89% of mutation carriers when accounting for cascade testing triggered after mutation-positive daughters were identified by screening. We present data on all carrier-probability thresholds, e.g., a 5% threshold identified 46% of mutation carriers while testing 10% of women.Conclusions: Different carrier-probability thresholds offered diverse tradeoffs between numbers of identified mutation carriers versus women tested. Low carrierprobability thresholds identified 90% of BRCA1/2 founder mutation carriers, without testing approximately 1 million U.S. Ashkenazi-Jewish women with lowest carrier probabilities.Impact: In general, this risk-based framework could provide useful new options to consider during eligibility-criteria development for population mutation screening.

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Implications of BRCA1, BRCA2 Gene in Overall Development and Prognosis of Breast Cancer

Manzoor

Koul

Baba

et al. 2022

Breast Cancer: From Bench to Personalized Medicine

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Performance of BRCA1/2 mutation prediction models in male breast cancer patients

Cited by 6 publications

References 41 publications

Validation of the BOADICEA model for predicting the likelihood of carrying pathogenic variants in eight breast and ovarian cancer susceptibility genes

Validation of the BOADICEA model for predicting the likelihood of carrying pathogenic variants in eight breast and ovarian cancer susceptibility genes

A Pragmatic Testing-Eligibility Framework for Population Mutation Screening: The Example of BRCA1/2

Implications of BRCA1, BRCA2 Gene in Overall Development and Prognosis of Breast Cancer

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