Hereditary breast and ovarian cancer: new genes, new treatments, new concepts.

摘要: In Germany, breast cancer is the most common malignant disease in women and ovarian gynecological tumor with highest mortality rate (e1). There may be a hereditary burden even if only two or more women, one young woman, family develop (Table 1). Current work has shown that this caused by monogenic polygenic inheritance which DNA repair genes are mutated (1). As yet there no differences between treatments provided for sporadic cancer, although indications targeted therapy effective BRCA1/BRCA2-associated tumors (2, 3). Retrospective studies reveal high level of sensitivity to platin derivatives BRCA-associated (4), initial clinical trials show good efficacy tolerability PARPs, poly ADP (adenosine diphosphate)-ribose polymerase inhibitors, mutation carriers advanced cancers (5, 6). PARPs particularly on cells carriers, they might also potentially used chemoprevention. Thanks multimodal screening, BRCA1/2 can diagnosed at an early stage (7, e2). The selection optimum examination methods intervals their possible effects subjects ongoing studies. efficient screening (e3). However, benefits risk-reducing prophylactic surgery have been confirmed (8). German Consortium Hereditary Breast Ovarian Cancer (Deutsches Konsortium fur Familiaren Brust- und Eierstockkrebs) centers 12 universities throughout Germany (http://www.krebsgesellschaft.de/onkoscout_zentren_familie_brustkrebs,85319.html—in German) (eBox 1) aims provide structured, validated genetic diagnostics resulting diagnostic therapeutic interventions oncology, via multidisciplinary approach. This not least thanks central recording inclusion criteria relating patients’ medical histories testing 2) genetic, histological, clinical, follow-up data Consortium’s database University Leipzig (Institute Medical Computing, Statistics Epidemiology [Institut Medizinische Informatik, Statistik Epidemiologie, IMISE]). Table 1 Family constellations empirical probability pathogenic BRCA gene mutations (percentage index patients evidence mutation, constellation; accuracy ±2%) ebox 1 List Germany Berlin Charite, Berlin Clinic Center representative: Prof. Dr. Ulrich Bick Cologne/Bonn Cologne Rita Schmutzler Dresden University Clinic, Dresden Technology Center Wolfgang Distler Dusseldorf Dusseldorf representatives: Janni, Dieter Niederacher Hannover Hannover School (MHH) Center Brigitte Schlegelberger Heidelberg Heidelberg Claus R. Bartram Kiel Kiel Walter Jonat, Prof. Norbert Arnold Leipzig Leipzig med. Briest Munich University Ludwig Maximilian Munich Center Alfons Meindl Munster Munster Clinic Project Manager: Peter Wieacker Ulm Ulm Rolf Kreienberg Wurzburg Wurzburg Tiemo Grimm ebox 2 Criteria analysis BRCA1 BRCA2 person (S3 guideline, 2008) Breast members, first before age 51 Breast three any age Breast member aged 36 younger Bilateral 51 younger Breast members Breast male female