A neoadjuvant phase II/III RCT for BRCA1/2-associated and familial triple negative breast cancer comparing carboplatin to docetaxel (neoFAM)

• Applicant: Privatdozentin Dr. Kerstin Rhiem
• Subject Area: Gynaecology and Obstetrics
• Term: from 2014 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 251130402

Breast cancer patients from high risk families with mutations in the BRCA1 or BRCA2 gene have a lifetime risk of about 60% for breast cancer and 20-40% for ovarian cancer. There is accumulating evidence from in vitro and retrospective in vivo studies, also from our own group, that BRCA-associated breast cancer exhibit preferential treatment response to DNA-intercalating substances (e.g. carboplatin) compared to antimicrotubulin agents (e.g. docetaxel). This can be functionally explained by the involvement of the BRCA genes in DNA double-strand repair that lead to homologous recombination deficiency in BRCA-negative cells and vulnerability to DNA-intercalating drugs. Triple-negative breast cancers (TNBC) share a BRCA1-like phenotype and are generally associated with shorter disease free and overall survival and currently account for 15-20% of all breast cancers and 25% of breast cancer-related deaths. Therefore the majority of TNBC might benefit from treatment with DNA-intercalating drugs. In such a hitherto first neoadjuvant randomised controlled trial we want to answer the following question: Is a platinum-based chemotherapy superior over a taxane-based chemotherapy for BRCA-associated breast cancer and familial TNBC? As a novel aspect we want to validate five biomarkers for BRCAness and neoadjuvant treatment efficacy. This study may also serve as a proof of concept study for sporadic breast cancers that present with a BRCAness phenotype and other targeted agents (e.g. PARP inhibitors).

• DFG Programme: Clinical Trials
• Participating Person: Professorin Dr. Rita Katharina Schmutzler