GeparSixto II期试验显示，三阴性乳腺癌（TNBC）患者的新辅助化疗方案中添加卡铂可以大幅提高患者的病理完全缓解率。每周应用紫杉醇/脂质体阿霉素（PM方案）时患者的病理缓解率为36.9%，添加卡铂后，患者的病理缓解率可以提升到53.2%(Von Minckwitz et al, Proc ASCO 2013)。
资讯详情：[ASCO POST]卡铂可提高三阴性乳腺癌病理缓解
2014年ASCO大会上的乳腺癌口头报告中，GeparSixto试验的最新结果评估了生殖系BRCA（gBRCA）突变或有乳腺癌或卵巢癌家族史的患者应用此方案的疗效。
研究方法
GeparSixto试验中的315位三阴性乳腺癌患者中，295位患者有足量DNA的全血样本。我们应用探针扩增技术和Fluidigm筛选（复发的BRCA1/2突变）技术检测gBRCA突变。两种方法结合可以使我们检测到大约60%的突变携带者。我们应用下一代测序技术对目前尚未发现突变的患者进行检测，找出其他的BRCA1/2突变或其他的乳腺癌易感基因。
研究结果
目前共发现了38位突变携带者（BRCA 1突变的有35人, BRCA 2突变的有3人，31个由中心实验室检测出来的，7个是由地区实验室检测出来的）。另外78位患者有乳腺癌家族史。179位患者既无突变基因，也无家族史。未发现风险组患者的总病理完全缓解率为40.2%，只有家族史的患者的总病理完全缓解率为44.9%，gBRCA基因突变的患者的总病理完全缓解率为57.9%。在PM方案中添加卡铂后，未发现风险组的患者病理完全缓解率增加了14%(优势比, OR 1.79)，只有家族史的患者病理完全缓解率增加了20%(OR 2.29)，gBRCA基因突变的患者病理完全缓解率增加了25% (OR 2.75) 。
结论
gBRCA突变和家族史是三阴性乳腺癌患者应用蒽环霉素/紫杉烷新辅助化疗后病理完全缓解率升高的预测因子。gBRCA突变的患者添加卡铂后疗效提升最显著。试验完成后更新的gBRCA突变分析将在会上公布。临床试验信息：NCT 01426880.
医脉通整理报道，转载请注明出处。
会议专题》》》2014年ASCO年会专题报道
阅读英文摘要
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.（Abstract No:1005）
Authors: Gunter Von Minckwitz, Eric Hahnen, Peter A. Fasching, et al.
Session Type: Oral Abstract Session
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.
