Klinikum rechts der Isar, aBteilung Gyn. Tumorgenetik, München.
Dtsch Arztebl Int. 2011 May;108(19):323-30. doi: 10.3238/arztebl.2011.0323. Epub 2011 May 13.
Every year, 60,000 women in Germany are found to have breast cancer, and 9000 to have ovarian cancer. Familial clustering of carcinoma is seen in about 20% of cases.
We selectively review relevant articles published up to December 2010 that were retrieved by a search in PubMed, and we also discuss findings from the experience of the German Consortium for Hereditary Breast and Ovarian Cancer.
High risk is conferred by the highly penetrant BRCA1 and BRCA2 genes as well as by other genes such as RAD51C. Genes for breast cancer that were originally designated as moderately penetrant display higher penetrance than previously thought in families with a hereditary predisposition. The role these genes play in DNA repair is thought to explain why tumors associated with them are sensitive to platin derivatives and PARP inhibitors. In carriers of BRCA1 and BRCA2, prophylactic bilateral mastectomy and adnexectomy significantly lowers the incidence of breast and ovarian cancer. Moreover, prophylactic adnexectomy also lowers the breast-and-ovarian-cancer-specific mortality, as well as the overall mortality. If a woman bearing a mutation develops cancer in one breast, her risk of developing cancer in the other breast depends on the particular gene that is mutated and on her age at the onset of disease.
About half of all monogenically determined carcinomas of the breast and ovary are due to a mutation in one or the other of the highly penetrant BRCA genes (BRCA1 and BRCA2). Women carrying a mutated gene have an 80% to 90% chance of developing breast cancer and a 20% to 50% chance of developing ovarian cancer. Other predisposing genes for breast and ovarian cancer have been identified. Clinicians should develop and implement evidence-based treatments on the basis of these new findings.
在德国，每年有 6 万名女性被诊断患有乳腺癌，9000 名女性被诊断患有卵巢癌。约 20%的病例中存在癌家族聚集现象。
我们有选择地综述了截至 2010 年 12 月在 PubMed 上检索到的相关文章，并讨论了德国遗传性乳腺癌和卵巢癌联合会的经验发现。
高风险由高度外显的 BRCA1 和 BRCA2 基因以及 RAD51C 等其他基因引起。最初被指定为中度外显的乳腺癌基因在具有遗传易感性的家族中显示出比以前认为的更高的外显率。这些基因在 DNA 修复中所起的作用解释了为什么与它们相关的肿瘤对铂衍生物和 PARP 抑制剂敏感。BRCA1 和 BRCA2 携带者行预防性双侧乳房切除术和附件切除术可显著降低乳腺癌和卵巢癌的发生率。此外，预防性附件切除术还降低了乳腺癌和卵巢癌特异性死亡率以及总死亡率。如果携带突变的女性在一侧乳房中发生癌症，其在另一侧乳房中发生癌症的风险取决于发生突变的特定基因和发病时的年龄。
约一半的乳腺和卵巢的单基因决定的癌归因于高外显的 BRCA 基因（BRCA1 和 BRCA2）之一的突变。携带突变基因的女性有 80%至 90%的机会患乳腺癌，有 20%至 50%的机会患卵巢癌。已经确定了其他乳腺癌和卵巢癌的易感基因。临床医生应根据这些新发现制定和实施循证治疗。
