Evaluation of the Dutch BRCA1/2 clinical genetic center referral criteria in an unselected early breast cancer population
Open accessAbstract
In this study, we evaluated the diagnostic value of the Dutch Clinical Genetic Center (CGC) referral guidelines for BRCA1/2 mutation testing in 903 early breast cancer patients, unselected for family history, diagnosed in a cancer hospital before the age of 50 years in 1974-2002; most prevalent Dutch pathogenic BRCA1/2 mutations had been analyzed on coded DNA in a research setting. Forty-nine (5.4%) of the patients were proven to be BRCA1/2 mutation carriers. We found that 78% and 69% of BRCA1 and BRCA2 mutation carriers identified met the criteria for referral to the CGC based on age, family history and synchronous multiple tumors; reflected by a combined sensitivity of 75.5% and specificity of 63.2%. More than half of the BRCA1 mutation carriers, that is, 58% had a triple-negative tumor. The highest AUC was obtained by shifting the age at diagnosis threshold criterion from 40 to 35 years and by adding a 'triple-negative breast cancer' criterion with an age threshold of 45 years; the specificity increased to 71.2%, whereas the sensitivity remained the same; that is, a referral of fewer patients will lead to the identification of at least the same number of BRCA1/2 mutation carriers. Two-thirds of the BRCA1/2 mutation carriers identified in this research setting had been referred for counseling and testing. Our results indicate that, awaiting a possibly more extended mutation screening of all breast cancer patients, the triple-negative status of a breast cancer should be added to the CGC referral criteria.
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A large proportion of patients were diagnosed before 1995, so many BRCA1/2 mutation carriers were unaware of their mutation status at diagnosis.
“Importantly, because a large proportion of patients were diagnosed before 1995, many BRCA1/2 mutation carriers were unaware of their mutation status at diagnosis.42,48”
From Impact of Age at Primary Breast Cancer on Contralateral Breast Cancer Risk in <i>BRCA1/2</i> Mutation Carriers (2016) · cites this paper as [48]
Family history data were gathered from clinical charts and may be of lower quality, although sufficient correlation with Clinical Genetic Center data was previously shown.
“Furthermore, the family history data we used were gathered from the clinical charts, and may therefore be of lower quality, even though previously we showed sufficient correlation with data from the Clinical Genetic Center.48”
From Impact of Age at Primary Breast Cancer on Contralateral Breast Cancer Risk in <i>BRCA1/2</i> Mutation Carriers (2016) · cites this paper as [48]
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- Authors
- van den Broek, A. J., de Ruiter, K., van 't Veer, L. J., Tollenaar, R. A. E. M., van Leeuwen, F. E., Verhoef, S., & Schmidt, M. K.
- Affiliations
- Leiden University Medical Center (NL)
- The Netherlands Cancer Institute (NL)
- Corresponding author
- Schmidt, Marjanka K
- Venue
- European Journal of Human Genetics
- Published
- 2014-08-20
- Volume
- 23
- Issue
- 5
- Pages
- 588-595
- ISSN
- 1018-4813 (ISSN-L)
- 1476-5438
- PMC
- PMC4402636
- OpenAlex
- W2058963482
- Cited by
- 18
- References
- 39
- Citations by year
- 2025: 3 · 2024: 1 · 2022: 3 · 2021: 1 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 3
- FWCI
- 1.53
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- European Journal of Human Genetics (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- KWF Kankerbestrijding (DCS-NKI 2009-4363, 2007-3839, DCS-NKI 2001‐2423, NKI 2009-4363, DCS-NKI 2007-3839, 2009 4363, NKI 2007–3839)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Health Sciences › Medicine › Pathology and Forensic Medicine › Breast Lesions and Carcinomas
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- BRCA1, BRCA2, hereditary breast cancer, early breast cancer, mutation testing, triple-negative breast cancer, diagnostic accuracy, family history (medicine), mutation carriers
- MeSH terms
- Adult, Breast Neoplasms, Female, Genetic Testing, Heterozygote, Humans, Middle Aged, Mutation, Neoplasm Staging, Netherlands, Referral and Consultation, Retrospective Studies, Sensitivity and Specificity, Biomarkers, Tumor, Reproducibility of Results, Germ-Line Mutation, Genes, BRCA1, Genes, BRCA2, Young Adult
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