European Journal of Human Genetics - Abstract of article: Evaluation of the Dutch BRCA1/2 clinical genetic center referral criteria in an unselected early breast cancer population

European Journal of Human Genetics - Abstract of article: Evaluation of the Dutch BRCA1/2 clinical genetic center referral criteria in an unselected early breast cancer population

European Journal of Human Genetics advance online publication 20 August 2014; doi: 10.1038/ejhg.2014.161

Evaluation of the Dutch BRCA1/2 clinical genetic center referral criteria in an unselected early breast cancer population
^EJHGOpen

Alexandra J van den Broek^1,2, Karen de Ruiter¹, Laura J van 't Veer², Rob A E M Tollenaar³, Flora E van Leeuwen¹, Senno Verhoef⁴ and Marjanka K Schmidt^1,2

1. ¹Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands
2. ²Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands
3. ³Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands
4. ⁴Family Cancer Clinic, Netherlands Cancer Institute, Amsterdam, the Netherlands

Correspondence: Dr MK Schmidt, Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam 1066 CX, the Netherlands. Tel: +31 (0)20 512 2487; Fax: +31(0)20 512 2322; E-mail: mk.schmidt@nki.nl

Received 28 February 2014; Revised 26 June 2014; Accepted 9 July 2014
Advance online publication 20 August 2014

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Abstract

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% ofBRCA1 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.