Pathological complete response (pCR) rates after carboplatin-containing neoadjuvant chemotherapy in patients with germline BRCA (gBRCA) mutation and triple-negative breast cancer (TNBC): Results from GeparSixto.

Breast Cancer - Triple-Negative/Cytotoxics/Local Therapy
Session Type and Session Title: 
Oral Abstract Session, Breast Cancer - Triple-Negative/Cytotoxics/Local Therapy
Abstract Number: 
J Clin Oncol 32:5s, 2014 (suppl; abstr 1005)
Gunter Von Minckwitz, Eric Hahnen, Peter A. Fasching, Jan Hauke, Andreas Schneeweiss, Christoph Salat, Mahdi Rezai, Jens U. Blohmer, Dirk Michael Zahm, Christian Jackisch, Bernd Gerber, Peter Klare, Sherko Kummel, Holger Eidtmann, Stefan Paepke, Valentina Nekljudova, Sibylle Loibl, Michael Untch, Rita K. Schmutzler, GBG and AGO-B Study Groups; German Breast Group/University Frankfurt, Neu-Isenburg, Frankfurt, Germany; University of Cologne, Cologne, Germany; Department of Obstetrics and Gynecology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany; University Hospital Heidelberg, Heidelberg, Germany; Hematology Oncology Clinic, Munich, Germany; Breast Center Duesseldorf, Louisen Hospital, Düsseldorf, Germany; Brustzentrum Sankt-Gertrauden-Krankenhaus, Berlin, Germany; Frauenklinik Gera, Gera, Germany; Sana Kliniken Offenbach, Offenbach, Germany; University Rostock, Rostock, Germany; Praxisklinik Krebsheilkunde, Berlin, Germany; Breast Cancer Centre, Kliniken Essen-Mitte, Evangelische Huyssens-Stiftung, Essen, Germany; University Kiel, Kiel, Germany; Department of Obstetrics and Gynecology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany; German Breast Group, Neu-Isenburg, Germany; German Breast Group/Sana Klinikum Offenbach, Neu-Isenburg, Germany; Department of Gynecology and Obstetrics and Multidisciplinary Breast Cancer Center, Helios Klinikum Berlin-Buch, Berlin, Germany; Center for Familial Breast and Ovarian Cancer and Center of Integrated Oncology, Cologne, Germany

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Abstract Disclosures


Background: We previously showed in participants with TNBC of the neoadjuvant phase II GeparSixto study (NCT01426880) that the addition of carboplatin can substantially improve the pCR rates from 36.9% with weekly paclitaxel/non-pegylated liposomal doxorubicin (PM) to 53.2% with PM plus weekly carboplatin (AUC2) (PMCb) (von Minckwitz et al, Proc ASCO 2013). We aimed to assess how far this benefit is correlated with gBRCA mutation or with a family history for breast or ovarian cancer. Methods: Full blood samples with sufficient amount of DNA were available in 295 (94%) out of 315 participants of GeparSixto with TNBC. We searched for gBRCA mutations by MLPA and Fluidigm screening for recurrent pathogenic BRCA1/2 alterations. In combination, both methods enable us to detect approximately 60% of all expected mutation carriers. Participants with so far undetected mutations are currently under investigation by employing next generation sequencing (NGS) techniques to detect additional pathogenic germline alterations in BRCA1/2 or other breast cancer predisposing genes. Results: At total of 38 mutation carriers (35 BRCA 1, 3 BRCA 2) have so far been identified (31 by central testing and 7 known results from local testing). Additional 78 patients have a known family breast cancer history. 179 patients have so far neither a mutation nor a family history. Overall pCR (ypT0 ypN0) rate increased from 40.2% in patients with no identified risk, to 44.9% in patients with family history only, to 57.9% for patients with gBRCA mutation. Adding carboplatin to PM increased the pCR rate by 14% (odds ratio, OR 1.79) in patients without increased risk, by 20% (OR 2.29) in patients with family history only, and by 25% (OR 2.75) for patients with gBRCA mutation. Conclusions: gBRCA mutation and family history are predictors for higher pCR rates after neoadjuvant anthracycline/taxane based chemotherapy in TNBC. Additive effect of carboplatin is most prominent in patients with gBRCA mutation. Updated results after complete gBRCA mutation analysis will be presented at the meeting. Clinical trial information: NCT 01426880.