[Hereditary breast cancer].
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.
Universitätsfrauenklinik, Vossstrasse 9, 69115, Heidelberg. bettina.schlehe@med.uni-heidelberg.de
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Schlehe
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Schmutzler
D051017:Apoptosis Regulatory Proteins; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D024161:Collagen Type XI / Q000037:antagonists & inhibitors; D004252:DNA Mutational Analysis; D042241:Early Diagnosis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D016462:Mammaplasty; D008408:Mastectomy; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000235:genetics / Q000601:surgery; D009386:Neoplastic Syndromes, Hereditary / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D010052:Ovariectomy; D011379:Prognosis; D018714:Radiotherapy, Adjuvant
D051017:Apoptosis Regulatory Proteins; C118024:BLID protein, human; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; C499319:COL11A2 protein, human; D024161:Collagen Type XI
Hereditäres Mammakarzinom.