循环肿瘤DNA对晚期乳腺癌疗效判断的价值
摘要
目的:分析循环肿瘤DNA(ctDNA)对晚期乳腺癌疗效判断的价值。方法:晚期乳腺癌患者60例,在每次化疗前、化疗后第1天及化疗结束后检测ctDNA、血清CEA和CA153水平,化疗2个疗程后行影像学检查评价疗效。结果:所有患者化疗后第1天ctDNA明显上升,21例PD患者在化疗2个疗程后血ctDNA较治疗前升高,差异有统计学意义(P<0.05),其中19例在化疗1个疗程后血ctDNA持续性升高,较影像学提前4周提示病情进展,而血清CEA、CA152水平与治疗前比较,差异均无统计学意义(P>0.05)。22例SD患者治疗后血清CEA、CA153及ctDNA水平与治疗前相似,差异均无统计学差异(P>0.05)。17例PR患者治疗后血ctDNA较治疗前明显下降,差异有统计学意义(P<0.05),而血清CEA、CA153治疗后轻微下降,与治疗前比较,差异无统计学意义(P>0.05)。ctDNA总变异数>5患者平均PFS为19.8周,中位PFS为16.8周,总变异数≤5患者平均PFS为72.4周,中位PFS为76.5周,两者差异性比较有统计学意义(P<0.05)。结论:动态检测循环肿瘤DNA可能有助于更早地判断疗效和预后,提前指导治疗方案的调整。
引文
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[3]Chen W, Zheng R, Baade PD, et al. Cancer statistics in China,2015[J]. CA Cancer J Clin, 2016, 66(2):115-132.
[4]Dawson SJ, Tsui DW, Murtaza M, et al. Analysis of circulating tumor DNA to monitor metastatic breast cancer[J]. N Engl J Med,2013, 368(13):1199-1209.
[5]Forshew T, Murtaza M, Parkinson C, et al. Noninvasive identification and monitoring of cancer mutations by targeted deep sequencing of plasma DNA[J]. Sci Transl Med, 2012, 4(136):136ra68.
[6]Nagata S, Hanayama R, Kawane K. Autoimmunity and the clearance of dead cells[J]. Cell, 2010, 140(5):619-630.
[7]Fleischhacker M, Schmidt B. Circulating nucleic acids(CNAs)and cancer--a survey[J]. Biochim Biophys Acta, 2007, 1775(1):181-232.
[8]Catarino R, Ferreira MM, Rodrigues H, et al. Quantification of free circulating tumor DNA as a diagnostic marker for breast cancer[J]. DNA Cell Biol, 2008, 27(8):415-421.
[9]Garcia-Murillas I.Schiavon G, Weigelt B, et al. Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer[J]. Sci Transl Med, 2015, 7(302):302ra133.
[10]Higgins MJ, Jelovac D, Barnathan E, et al. Detection of tumor PIK3CA status in metastatic breast cancer using peripheral blood[J]. Clin Cancer Res, 2012, 18(12):3462-3469.
[11]Radpour R, Barekati Z, Kohler C, et al. Hypermethylation of tumor suppressor genes involved in critical regulatory pathways for developing a blood-based test in breast cancer[J]. PLoS One,2011, 6(1):e16080.
[12]Silva JM, Silva J, Sanchez A, et al. Tumor DNA in plasma at diagnosis of breast cancer patients is a valuable predictor of disease-free survival[J]. Clin Cancer Res, 2002, 8(12):3761-3766.