PDF(Pubmed)
Abstract：
UNASSIGNED: The absence of breast cancer cells in surgical specimens, i.e., pathological complete response (pCR), is widely recognized as a favorable prognostic factor after neoadjuvant therapy. In contrast, the presence of disease at surgery characterizes a prognostically heterogeneous group of patients. Here, we challenged circulating microRNAs (miRNAs) at the end of neoadjuvant therapy as potential prognostic biomarkers in the NeoALTTO study.
UNASSIGNED: Patients treated within the trastuzumab arm (i.e., pre-operative weekly trastuzumab for 6 weeks followed by the addition of weekly paclitaxel for 12 weeks; post-operative FEC for 3 cycles followed by trastuzumab up to complete 1 year of treatment) were randomized into a training (n= 54) and testing (n= 72) set. RT-PCR-based high-throughput miRNA profile was performed on plasma samples collected at the end of neoadjuvant treatment of both sets. After normalization, circulating miRNAs associated with event free survival (EFS) were identified by univariate and multivariate Cox regression model.
UNASSIGNED: Starting from 23 circulating miRNAs associated with EFS in the training set, we generated a 3-circulating miRNA prognostic signature consisting of miR-185-5p, miR-146a-5p, miR-22-3p, which was confirmed in the testing set. The 3-circulating miRNA signature showed a C-statistic of 0.62 (95% confidence interval [95%CI] 0.53-0.71) in the entire study cohort. By resorting to a multivariate Cox regression model we found a statistical significant interaction between the expression values of miR-194-5p and pCR status (p.interaction =0.005) with an estimate Hazard Ratio (HR) of 1.83 (95%CI 1.14- 2.95) in patients with pCR, and 0.87 (95%CI 0.69-1.10) in those without pCR. Notably, the model including this interaction along with the abovementioned 3-circulating miRNA signature provided the highest discriminatory capability with a C-statistic of 0.67 (95%CI 0.58-0.76).
UNASSIGNED: Circulating miRNAs are informative to identify patients with different prognosis among those with heterogeneous response after trastuzumab-based neoadjuvant treatment, and may be an exploitable tool to select candidates for salvage adjuvant therapy.
UNASSIGNED: Patients treated within the trastuzumab arm (i.e., pre-operative weekly trastuzumab for 6 weeks followed by the addition of weekly paclitaxel for 12 weeks; post-operative FEC for 3 cycles followed by trastuzumab up to complete 1 year of treatment) were randomized into a training (n= 54) and testing (n= 72) set. RT-PCR-based high-throughput miRNA profile was performed on plasma samples collected at the end of neoadjuvant treatment of both sets. After normalization, circulating miRNAs associated with event free survival (EFS) were identified by univariate and multivariate Cox regression model.
UNASSIGNED: Starting from 23 circulating miRNAs associated with EFS in the training set, we generated a 3-circulating miRNA prognostic signature consisting of miR-185-5p, miR-146a-5p, miR-22-3p, which was confirmed in the testing set. The 3-circulating miRNA signature showed a C-statistic of 0.62 (95% confidence interval [95%CI] 0.53-0.71) in the entire study cohort. By resorting to a multivariate Cox regression model we found a statistical significant interaction between the expression values of miR-194-5p and pCR status (p.interaction =0.005) with an estimate Hazard Ratio (HR) of 1.83 (95%CI 1.14- 2.95) in patients with pCR, and 0.87 (95%CI 0.69-1.10) in those without pCR. Notably, the model including this interaction along with the abovementioned 3-circulating miRNA signature provided the highest discriminatory capability with a C-statistic of 0.67 (95%CI 0.58-0.76).
UNASSIGNED: Circulating miRNAs are informative to identify patients with different prognosis among those with heterogeneous response after trastuzumab-based neoadjuvant treatment, and may be an exploitable tool to select candidates for salvage adjuvant therapy.
摘要：
未经证实：手术标本中没有乳腺癌细胞，即，病理完全缓解（pCR），被广泛认为是新辅助治疗后的有利预后因素。相比之下,手术中疾病的存在是预后异质性患者组的特征。这里,在NeoALTTO研究中,我们在新辅助治疗结束时将循环microRNAs(miRNAs)作为潜在的预后生物标志物提出了挑战.
UNASSIGNED：曲妥珠单抗臂内治疗的患者（即，术前每周曲妥珠单抗治疗6周,然后每周添加紫杉醇治疗12周;术后FEC治疗3个周期,然后曲妥珠单抗治疗1年)被随机分为训练组(n=54)和测试组(n=72).对两组新辅助治疗结束时收集的血浆样品进行基于RT-PCR的高通量miRNA谱。归一化后,通过单变量和多变量Cox回归模型鉴定与无事件生存期(EFS)相关的循环miRNA.
UNASSIGNED：从训练集中与EFS相关的23个循环miRNA开始，我们产生了一个由miR-185-5p组成的3循环miRNA预后标签，miR-146a-5p,miR-22-3p,这在测试集中得到了证实。3-循环miRNA签名在整个研究队列中显示0.62(95%置信区间[95CI]0.53-0.71)的C统计量。通过采用多变量Cox回归模型，我们发现miR-194-5p的表达值与pCR状态之间存在统计学上的显着相互作用（p。交互作用=0.005），pCR患者的估计危险比（HR）为1.83（95CI1.14-2.95），无pCR的患者为0.87（95CI0.69-1.10）。值得注意的是,包括这种相互作用以及上述3个循环miRNA特征的模型提供了最高的辨别能力,C统计量为0.67(95CI0.58-0.76).
UASSIGNED：循环miRNAs可用于识别基于曲妥珠单抗的新辅助治疗后具有异质性反应的患者中具有不同预后的患者，并且可能是选择挽救辅助治疗候选人的可利用工具。
UNASSIGNED：曲妥珠单抗臂内治疗的患者（即，
UNASSIGNED：从训练集中与EFS相关的23个循环miRNA开始，
UASSIGNED：循环miRNAs可用于识别基于曲妥珠单抗的新辅助治疗后具有异质性反应的患者中具有不同预后的患者，
