Serum DNA methylation for monitoring response to neoadjuvant chemotherapy in breast cancer patients.
Serum DNA methylation for monitoring response to neoadjuvant chemotherapy in breast cancer patients.
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DOI：
10.1002/ijc.27526
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发表时间：
2012-10-01
影响因子：
6.4
通讯作者：
Evron, Ella
中科院分区：
文献类型：
--
作者：
Avraham, Ayelet;Uhlmann, Ronit;Shperber, Aino;Birnbaum, Miriam;Sandbank, Judith;Sella, Avishay;Sukumar, Saraswati;Evron, Ella
患有大的或不可手术的乳腺癌的患者通常接受新辅助化疗以促进肿瘤的完全切除并能够保留乳房。然而，目前用于评价治疗期间的反应的方法是有限的，并且治疗的实际效果仅在完成化疗后的手术中被认识到。反应的及时评估可以允许个体定制的治疗和节省无效的药物和不必要的毒性。在此，我们认为血清中肿瘤衍生的DNA甲基化可能反映肿瘤负荷的变化，并允许早期识别应答者与无应答者。在这项初步研究中，我们收集了52例局部晚期乳腺癌患者在新辅助化疗期间的7个连续血清样本。我们选择了RASSF1，它在超过80%的肿瘤中被甲基化，用于血清分析。使用“甲基化敏感PCR和高分辨率熔解”，我们检测了21例患者治疗前血清中的RASSF1甲基化。在4名达到完全病理学缓解的患者中，血清中的RASSF1甲基化在治疗早期变得不可检测。相比之下，在17例具有部分或最小病理学应答的患者中，血清RASSF1甲基化持续时间更长或在整个治疗期间持续（完全应答与部分应答p = 0.02）。这些发现支持进一步开发用于监测新辅助治疗期间反应的该测定。
Patients with large or nonoperable breast cancers often receive neoadjuvant chemotherapy to facilitate full resection of the tumor and enable conservation of the breast. However, currently available methods for evaluation of response during therapy are limited and the actual effect of the treatment is only recognized at surgery upon completion of chemotherapy. Timely assessment of response could allow individual tailoring of the treatment and save noneffective drugs and unnecessary toxicity. Here, we suggest that tumor derived DNA methylation in the serum may reflect changes in tumor burden and allow early recognition of responders versus nonresponders. In this pilot study, we collected 7 consecutive serum samples from 52 patients with locally advanced breast cancer during neoadjuvant chemotherapy. We selected RASSF1, which was methylated in more than 80% of the tumors, for serum analysis. Using the “methylation sensitive PCR and high resolution melting,” we detected RASSF1 methylation in the serum of 21 patients prior to therapy. In four patients who achieved complete pathological response, RASSF1 methylation in the serum became undetectable early during therapy. In contrast, in 17 patients that had partial or minimal pathological response, serum RASSF1 methylation persisted longer or throughout the treatment (complete versus partial response p = 0.02). These findings support further development of this assay for monitoring response during neoadjuvant therapy.
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影响因子：
6.4
作者：
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