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首页> 外文期刊>EBioMedicine >Identifying Circulating Tumor DNA Mutation Profiles in Metastatic Breast Cancer Patients with Multiline Resistance
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Identifying Circulating Tumor DNA Mutation Profiles in Metastatic Breast Cancer Patients with Multiline Resistance

机译：识别具有多线耐药的转移性乳腺癌患者的循环肿瘤DNA突变谱

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Purpose In cancer patients, tumor gene mutations contribute to drug resistance and treatment failure. In patients with metastatic breast cancer (MBC), these mutations increase after multiline treatment, thereby decreasing treatment efficiency. The aim of this study was to evaluate gene mutation patterns in MBC patients to predict drug resistance and disease progression. Method A total of 68 MBC patients who had received multiline treatment were recruited. Circulating tumor DNA (ctDNA) mutations were evaluated and compared among hormone receptor (HR)/human epidermal growth factor receptor 2 (HER2) subgroups. Results The baseline gene mutation pattern (at the time of recruitment) varied among HR/HER2 subtypes. BRCA1 and MED12 were frequently mutated in triple negative breast cancer (TNBC) patients, PIK3CA and FAT1 mutations were frequent in HR+ patients, and PIK3CA and ERBB2 mutations were frequent in HER2+ patients. Gene mutation patterns also varied in patients who progressed within either 3?months or 3–6?months of chemotherapy treatment. For example, in HR+ patients who progressed within 3?months of treatment, the frequency of TERT mutations significantly increased. Other related mutations included FAT1 and NOTCH4 . In HR+ patients who progressed within 3–6?months, PIK3CA , TP53 , MLL3 , ERBB2 , NOTCH2, and ERS1 were the candidate mutations. This suggests that different mechanisms underlie disease progression at different times after treatment initiation. In the COX model, the ctDNA TP53 + PIK3CA gene mutation pattern successfully predicted progression within 6?months. Conclusion ctDNA gene mutation profiles differed among HR/HER2 subtypes of MBC patients. By identifying mutations associated with treatment resistance, we hope to improve therapy selection for MBC patients who received multiline treatment.
机译：目的在癌症患者中，肿瘤基因突变导致耐药性和治疗失败。在转移性乳腺癌（MBC）患者中，这些突变在多线治疗后增加，从而降低了治疗效率。这项研究的目的是评估MBC患者的基因突变模式，以预测耐药性和疾病进展。方法总共招募了接受多线治疗的68例MBC患者。评价并比较激素受体（HR）/人表皮生长因子受体2（HER2）亚组之间循环肿瘤DNA（ctDNA）突变。结果基线基因突变模式（在招募时）在HR / HER2亚型中有所不同。 BRCA1和MED12在三阴性乳腺癌（TNBC）患者中经常发生突变，HR +患者中PIK3CA和FAT1突变频繁，而HER2 +患者中PIK3CA和ERBB2突变频繁。在化疗后3个月或3到6个月内进展的患者，基因突变模式也有所不同。例如，在治疗后3个月内进展的HR +患者中，TERT突变的频率显着增加。其他相关的突变包括FAT1和NOTCH4。在3到6个月内进展的HR +患者中，PIK3CA，TP53，MLL3，ERBB2，NOTCH2和ERS1是候选突变。这表明在治疗开始后的不同时间，疾病发展的基础是不同的机制。在COX模型中，ctDNA TP5​​3 + PIK3CA基因突变模式成功地预测了6个月内的进展。结论MBC患者的HR / HER2亚型之间ctDNA基因突变谱存在差异。通过鉴定与治疗耐药性相关的突变，我们希望改善接受多线治疗的MBC患者的治疗选择。

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