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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.
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
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.
Abstracts by Gunter Von Minckwitz:
A model for trial level prediction of long term outcome based on pathological complete response (pCR) after neoadjuvant chemotherapy for early-stage breast cancer (EBC).Meeting: 2016 ASCO Annual Meeting | Abstract No: 1031
A randomized phase II trial to assess the efficacy of paclitaxel and olaparib in comparison to paclitaxel / carboplatin followed by epirubicin / cyclophosphamide as neoadjuvant chemotherapy in patients with HER2-negative early breast cancer and homologous recombination deficiency (HRD): GeparOLA.Meeting: 2016 ASCO Annual Meeting | Abstract No: TPS1096
Brain Metastases in Breast Cancer Network Germany (BMBC, GBG 79): Treatment patterns and clinical outcome of more than 1000 patients with brain metastases from breast cancer.Meeting: 2016 ASCO Annual Meeting | Abstract No: 2070
Presentations by Gunter Von Minckwitz:
Impact of treatment characteristics on response of different breast cancer subtypes: Pooled multilayer analysis of the German neoadjuvant chemotherapy trials.Meeting: 2010 ASCO Annual Meeting Abstract No: 501Session: Predictors of Response to Preoperative Therapy: Where are We- (Clinical Science Symposium)