Tumor burden monitoring using cell-free tumor DNA could be limited by tumor heterogeneity in advanced breast cancer and should be evaluated together with radiographic imaging.
Tumor burden monitoring using cell-free tumor DNA could be limited by tumor heterogeneity in advanced breast cancer and should be evaluated together with radiographic imaging.
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DOI：
10.1186/s12885-017-3185-9
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发表时间：
2017-03-22
期刊：
影响因子：
3.8
通讯作者：
Romero A
中科院分区：
文献类型：
--
作者：
García-Saenz JA;Ayllón P;Laig M;Acosta-Eyzaguirre D;García-Esquinas M;Montes M;Sanz J;Barquín M;Moreno F;Garcia-Barberan V;Díaz-Rubio E;Caldes T;Romero A
准确测量乳腺癌疾病中的肿瘤负荷对于改善患者的临床管理至关重要。在这项研究中，我们根据RECIST标准和肿瘤标志物定量评估PIK 3CA突变等位基因分数的波动是否与肿瘤缓解相关。使用E542 K、E545 K和H1047 R的罕见突变试验，通过数字PCR分析了86份血浆样本。将突变cfDNA和肿瘤标志物CA 15 -3和CEA与放射成像进行比较。FFPE样本中的PIK 3CA突变状态与循环肿瘤DNA（ctDNA）之间的一致性为中度（K = 0.591; 95%IC = 0.371-0.811）。将分析限制于转移性患者，我们发现在液体和固体活检中评估的PIK 3CA突变状态之间具有良好的一致性（K = 0.798 95%; IC = 0.586-1）。8例中7例ctDNA呈波动性变化，与肿瘤标志物15.3和CEA相关，Pearson相关系数分别为0.99 ~ 0.46和0.99 ~ 0.38。类似地，PIK 3CA突变等位基因分数的波动总是与图像上观察到的病变大小的变化相关，尽管在两种情况下，它与RECIST标准定义的治疗反应无关。血浆样品中致癌突变的定量可用于监测治疗结果。然而，在晚期疾病中，它可能受到肿瘤异质性的限制，应与放射学成像一起进行评估。本文的在线版本（doi：10.1186/s12885-017-3185-9）包含补充材料，可供授权用户使用。
Accurate measurement of tumor burden in breast cancer disease is essential to improve the clinical management of patients. In this study, we evaluate whether the fluctuations in the fraction of PIK3CA mutant allele correlates with tumor response according to RECIST criteria and tumor markers quantification. Eighty six plasma samples were analyzed by digital PCR using Rare Mutation Assays for E542K, E545K and H1047R. Mutant cfDNA and tumor markers CA15-3 and CEA were compared with radiographic imaging. The agreement between PIK3CA mutation status in FFPE samples and circulating tumor DNA (ctDNA) was moderate (K = 0.591; 95% IC = 0.371–0.811). Restricting the analysis to the metastatic patients, we found a good agreement between PIK3CA mutation status assessed in liquid and solid biopsy (K = 0.798 95%; IC = 0.586–1). ctDNA showed serial changes with fluctuations correlating with tumor markers 15.3 and CEA in 7 out of 8 cases with Pearson correlation coefficients ranging from 0.99 to 0.46 and from 0.99 to 0.38 respectively. Similarly, fluctuations in the fraction of PIK3CA mutant allele always correlated with changes in lesion size seen on images, although in two cases it did not correlate with treatment responses as defined by RECIST criteria. oncogenic mutation quantification in plasma samples can be useful to monitor treatment outcome. However, it might be limited by tumor heterogeneity in advanced disease and it should be evaluated together with radiographic imaging. The online version of this article (doi:10.1186/s12885-017-3185-9) contains supplementary material, which is available to authorized users.