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Hereditäres Mammakarzinom

Hereditary breast cancer

Zusammenfassung

Zehn Prozent aller Mammakarzinome entstehen auf der Grundlage hereditärer Faktoren, darunter die Hälfte durch Mutationen in den Genen BRCA1 oder BRCA2, die mit einer Erkrankungswahrscheinlichkeit für Brustkrebs von 60–80% und für Eierstockkrebs von 20–40% einhergehen. Seit der Beschreibung der BRCA-Gene in den 1990er Jahren wurden in Deutschland Richtlinien für ein interdisziplinäres Konzept etabliert, um Hochrisikofamilien zu identifizieren und hinsichtlich präventiver Möglichkeiten zu betreuen. Eine Früherkennung ab dem 25. Lebensjahr mittels Mammasonographie, Mammographie und MRT erlaubt eine Diagnose im frühen Stadium. Prophylaktische Operationen an der Brust und den Adnexen bewirken eine drastische Reduktion der Erkrankungswahrscheinlichkeit für das Mamma- und Ovarialkarzinom. In 12 spezialisierten Zentren in Deutschland wird eine Evaluation der angebotenen präventiven Möglichkeiten sowie die Etablierung und Prüfung spezieller therapeutischer Strategien beim BRCA-assoziierten Mammakarzinom unter Studienbedingungen vorangetrieben. Ein Meilenstein ist die Entdeckung eines ersten molekularen Targets, eines PARP-Inhibitors, welcher gezielt BRCA-defiziente Tumorzellen angreift und hervorragend verträglich ist. Die Teilnahme an einer weltweiten Phase-II-Studie im metastasierten Stadium wird über die spezialisierten Zentren angeboten.

Abstract

Ten per cent of all breast cancer cases have a strong hereditary component in which half carry a deleterious mutation in the high penetrance genes BRCA1 or BRCA2. These genes confer a lifetime risk of 60–80% for breast cancer and 20–40% for ovarian cancer. Since the identification of these genes in the mid-1990s, an interdisciplinary approach was established in 12 specialized university-based centres in Germany for identifying high-risk families that enables genetic testing and preventive clinical options. It could be demonstrated that ultrasound, mammography, and breast MRI allow the identification of early breast cancer stages. Prophylactic mastectomy and salpingo-oophorectomy reduce breast and ovarian cancer incidence considerably. New therapeutic and preventive strategies are being validated in ongoing clinical studies. Most recently a new molecular target, a PARP inhibitor, was developed that targets specifically BRCA-deficient tumour cells. Participation in a phase II study for metastatic breast and ovarian cancer is available through the centres. Accompanying scientific studies of over 4,500 DNA samples from BRCA1/2-negative high-risk families are moreover being examined for other predisposing genes.

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Correspondence to B. Schlehe.

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Schlehe, B., Schmutzler, R. Hereditäres Mammakarzinom. Chirurg 79, 1047 (2008). https://doi.org/10.1007/s00104-008-1556-0

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Schlüsselwörter

  • Hereditäres Mammakarzinom
  • Lebenszeitrisiko
  • BRCA-Mutation
  • Prophylaktische Operationen
  • Früherkennung

Keywords

  • Hereditary breast cancer
  • Lifetime risk
  • BRCA mutation
  • Prophylactic surgery
  • Early cancer detection