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Hereditärer Brustkrebs

Hereditary breast cancer

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Zusammenfassung

Die Diagnose Brustkrebs vor dem 40. Lebensjahr ist mit einem erhöhten Krebserkrankungsrisiko auch für die Angehörigen verbunden. Wegen des gemeinsamen Auftretens spricht man dann vom hereditären Mamma- und Ovarialkarzinom. Etwa 25–55% dieser familiären Erkrankungen werden durch Keimbahnmutationen der Krebssuszeptibilitätsgene BRCA1 oder BRCA2 zugeschrieben, etwa 5–10% anderen bekannten Tumordispositionssyndromen. Die verbleibenden Erkrankungen werden durch bisher nicht bekannte Gene erklärt. BRCA1 und BRCA2 sind autosomal-dominante Gene mit verminderter Penetranz und kodieren für sog. Tumorsuppressorproteine. Mutationen dieser Gene führen meist zum Ausfall des Allels. Ausfall auch des zweiten Allels führt zum Verlust der entsprechenden Proteine und erleichtert die maligne Transformation. Die Kenntnisse über die genetischen Ursachen haben Implikationen für die Beratung und Behandlung der ratsuchenden Frauen. Durch individuell abgestimmte Diagnostik und Eingriffe kann die Früherkennung individuell optimiert und das Erkrankungsrisiko für die einzelne Ratsuchende relevant gesenkt werden. In diesem Review werden die aktuellen Daten sowie das typische Vorgehen bei hereditärem Risiko für Mamma- und Ovarialkarzinom erläutert.

Abstract

Breast cancer in women under 40 years old is associated with an elevated risk of cancer also in first degree relatives. The term hereditary breast and ovarian cancer syndrome (HBOC) is derived from the frequent occurrence of both forms of cancer in these families. Approximately 25–55% of these hereditary cancers can be explained by germline mutations of the susceptibility genes BRCA 1 and BRCA2 and 5–10% by other syndromes of cancer susceptibility. The remaining diseases are explained by mutations in other genes. BRCA1 and BRCA2 mutations are autosomal dominant with reduced penetrance and coding for tumor suppressor genes. Mutations in these genes often lead to loss of the allele and loss of the second allele leads to loss of function of the corresponding protein and facilitates malignant transformation. Knowledge about genetic reasons has implications for counselling and therapy of individuals seeking advice. Employing individually adjusted measures, early detection can be optimized and the risk of cancer can be decreased. In this article the current data and recommendations with regard to risk of hereditary breast and ovarian cancer are reviewed.

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Interessenkonflikt

Der korrespondierende Autor weist auf folgende Beziehungen hin: Prof. Dr. med. Christoph Thomssen ist als Referent und in Advisory Boards für die Firmen Sanofi-Aventis, Pfizer, Novartis, Astra-Zeneca tätig.

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  1. Universitätsklinik und Poliklinik für Gynäkologie, Martin-Luther-Universität, Ernst-Grube-Straße 40, 06120, Halle (Saale), Deutschland

    C. Thomssen &  D. Wand

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  1. C. Thomssen
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  2. D. Wand
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Correspondence to C. Thomssen.

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Thomssen, C., Wand, D. Hereditärer Brustkrebs. Onkologe 18, 216–223 (2012). https://doi.org/10.1007/s00761-011-2095-8

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