gms | German Medical Science

BRCA1 or BRCA2 associated breast cancer (BrCa) account for about 5% of all cases. Medical attendance within large cohort studies all over the world have uncovered specific clinical features and disease courses of this genetically distinct subgroup. BRCA1 associated BrCa presents with a highly aggressive histological phenotype that is mirrored by a high growth rate and a worse outcome of the disease. Moreover, functional studies on the BRCA genes have revealed a crucial impact in the DNA douple strand repair process. Subsequent clinical and in vitro studies could prove that BRCA associated BrCa responds extremely well to chemotherapy thereby raising survival rates to those of sporadic BrCa. Due to the specific molecular alterations, DNA intercalating agents like platinum seem to be very potent while well approved substances like antracyclines or taxanes are less effective. Very recently, it has been shown that inhibition of poly-(ADP-ribose) polymerase, a key molecule in base excision repair, leads to apoptosis of BRCA deficient cells and thereby constitutes a potential molecular target for less toxic therapeutic strategies (Farmer et al. Nature 434: 917ff, 2005).

In order to promote translational studies in this well-characterized but rare subgroup of BrCa the German consortium for hereditary breast and ovarian cancer comprising 12 university based interdisciplinary centres has established a clinical study group that will now offer specific therapeutic regimens within prospective randomized trials in order to gain prompt and reliable data on potential therapeutic improvements. Study protocols and inclusion criteria will be presented in detail.