Schlehe B, Schmutzler R
Universitätsfrauenklinik, Vossstrasse 9, 69115, Heidelberg.
Chirurg. 2008 Nov;79(11):1047-54. doi: 10.1007/s00104-008-1556-0.
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.
所有乳腺癌病例中有10%具有很强的遗传因素,其中一半在高外显率基因BRCA1或BRCA2中携带有害突变。这些基因赋予患乳腺癌60 - 80%的终生风险以及患卵巢癌20 - 40%的终生风险。自20世纪90年代中期这些基因被鉴定以来,德国12个以大学为基础的专业中心建立了一种跨学科方法,用于识别高风险家族,该方法能够进行基因检测并提供预防性临床选择。已证实超声、乳腺X线摄影和乳腺磁共振成像能够识别早期乳腺癌阶段。预防性乳房切除术和输卵管卵巢切除术可大幅降低乳腺癌和卵巢癌的发病率。新的治疗和预防策略正在正在进行的临床研究中得到验证。最近开发了一种新的分子靶点——一种聚(ADP - 核糖)聚合酶(PARP)抑制剂,它专门针对BRCA缺陷的肿瘤细胞。通过这些中心可以参与转移性乳腺癌和卵巢癌的II期研究。此外,正在对来自BRCA1/2阴性高风险家族的4500多个DNA样本进行相关科学研究,以寻找其他易感基因。