ASCO最新进展 — What? — 什么是HER2+乳腺癌基线 该研究在新辅助治疗前获得的33名HER2+乳腺癌I-III期患者的组织活检样本上,使用一个由520个癌症相关基因组成的覆盖1.6MB人类基因组的panel进行基于捕获的靶向测序。研究对象的平均年龄为53岁。用多元分析方法分析基因组改变与病理反应的相关性。 参与者大多数为II期(67%,22/33),30%(10/33)为III期,3%(1/33)为I期患者。58%(19/33)为HR+, 42%(14/33)为HR-。基线样本的突变谱显示,共有145个基因发生了349个突变,其中TP53、CDK12和PIK3CA是最常见的3个突变基因。新辅助方案包括曲妥珠单抗和HER2抑制剂(即pertuzumab或拉帕替尼)。15例患者使用单一HER2抑制剂;18例患者使用双HER2抑制剂。HR+患者也接受内分泌治疗(19/33),联合曲妥珠单抗和HER2抑制剂。完全病理反应(pCR)发生率为45.5%(15/33)。有意思的是,ROS1拷贝数扩增(CANs)仅在获得pCR的患者中被识别(p = 0.033)。相比之下,CCND1、FGF19、FGF3、FGF4、SPOP、HNF1B、BRIP1中PIK3CA和CNAs的错义突变,在pCR患者中呈现出较少发生突变的趋势(p值在0.05-0.1之间)。以前的报道表明,HER2+患者的pCR率与HR状态有关。然而,我们的数据显示,基于HR状态或新辅助治疗方案,患者的病理反应具有可比性。 该项研究证实,获得pCR的患者与未获得pCR的患者之间存在明显的突变谱。但是为了证实这些发现,还需要进行更大规模的进一步研究。 Background: The standard management of early stage human epidermal growth factor receptor 2 (HER2) positive (+) breast cancer (BC) involves neoadjuvant therapy with combination of chemotherapy and HER2-targeted therapy followed by surgery. However, diverse pathologic responses were observed. We interrogated whether baseline genomic heterogeneity contributes to the varied therapeutic responses. Methods: Capture-based targeted sequencing using a panel consisting of 520 cancer-related genes, spanning 1.6MB of human genome, was performed on tissue biopsy samples, obtained prior to neoadjuvant therapy, of 33 HER2+ women with stage I-III BC. The median age of the cohort was 53. The correlation between genomic alterations and pathologic response were analyzed by multivariate analysis. Results: A majority of them was diagnosed with stage II (67%, 22/33), while 30% (10/33) had stage III and 3% (1/33) had stage I disease. 58% (19/33) were HR+ and 42% (14/33) were HR-. Mutation profiling of baseline samples revealed 349 mutations spanning 145 genes, with TP53, CDK12 and PIK3CA being the top 3 most frequently mutated genes. Neoadjuvant regimen was comprised of trastuzumab and HER2 inhibitor (i.e. pertuzumab or lapatinib). 15 patients used single HER2 inhibitor;18 used dual HER2 inhibitors. Endocrine therapy was also administered to HR+ patients (19/33) in combination with trastuzumab and HER2 inhibitor. Complete pathologic response (pCR) was observed in 45.5% (15/33) of patients. Interestingly, ROS1 copy number amplifications (CANs) were only identified in patients achieved pCR (p = 0.033). In contrast, missense mutations in PIK3CA and CNAs in CCND1, FGF19, FGF3, FGF4, SPOP, HNF1B and BRIP1 showed a trend of being less likely to mutate in pCR patients (p values between 0.05-0.1). Previous reports have suggested that pCR rates in HER2+ patients are associated with HR status. However, our data revealed comparable pathologic response of patients based on either HR status or neoadjuvant regimen. Conclusions: Our data revealed a distinct mutational profile between patients achieved pCR vs patients did not. Further studies with a larger cohort are required to confirm these findings. 原文链接:http://abstracts./239/AbstView_239_261539.html 医药学术推广找我们 扫描下方二维码联络 |
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