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Erschienen in: Breast Cancer Research and Treatment 3/2012

01.08.2012 | Epidemiology

Double heterozygosity for mutations in BRCA1 and BRCA2 in German breast cancer patients: implications on test strategies and clinical management

verfasst von: Simone Heidemann, Christine Fischer, Christoph Engel, Barbara Fischer, Lana Harder, Brigitte Schlegelberger, Dieter Niederacher, Timm O. Goecke, Sandra C. Doelken, Nicola Dikow, Walter Jonat, Susanne Morlot, Rita C. Schmutzler, Norbert K. Arnold

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 3/2012

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Abstract

Double heterozygosity for disease-causing BRCA1 and BRCA2 mutations is a very rare condition in most populations. Here we describe genetic and clinical data of eight female double heterozygotes (DH) for BRCA1 and BRCA2 mutations found in a cohort of 8162 German breast/ovarian cancer families and compare it with the data of their single heterozygous relatives and of the index patients of the German Consortium for Hereditary Breast and Ovarian Cancer. Furthermore, we analyze the phenotypic features of these patients with respect to age at onset of first cancer, first breast/ovarian cancer and the number of disease manifestations and compare them to that of published Caucasian female DHs and their single heterozygous female relatives. German DHs were not significantly younger at diagnosis of first breast cancer than the single heterozygous index patients of the German Consortium. However, if the data of our study were pooled with that of the literature, DHs were substantially younger at onset of first cancer (mean age 40.4 years, 95 % CI = 36.6–44.1) than their single heterozygous female relatives (mean age 51.9 years, 95 % CI = 46.8–57.0). The two groups also differed concerning the onset of first breast cancer (mean age 40.6 years, 95 % CI = 36.6–44.5 vs. 52.6, 95 % CI = 47.5–57.6). In addition, DHs had a more severe disease than their female relatives carrying a single BRCA mutation (1.4 vs. 0.6 manifestations per person). In contrast to Ashkenazi Jewish females, Caucasian DH females might develop breast cancer at an earlier age and have a more severe disease than single heterozygous BRCA mutation carriers. Therefore, DHs may benefit from more intensive surveillance programs/follow-up care and prophylactic surgery.
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Metadaten
Titel
Double heterozygosity for mutations in BRCA1 and BRCA2 in German breast cancer patients: implications on test strategies and clinical management
verfasst von
Simone Heidemann
Christine Fischer
Christoph Engel
Barbara Fischer
Lana Harder
Brigitte Schlegelberger
Dieter Niederacher
Timm O. Goecke
Sandra C. Doelken
Nicola Dikow
Walter Jonat
Susanne Morlot
Rita C. Schmutzler
Norbert K. Arnold
Publikationsdatum
01.08.2012
Verlag
Springer US
Erschienen in
Breast Cancer Research and Treatment / Ausgabe 3/2012
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-012-2050-4

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