Correlation of Methylated Circulating Tumor DNA With Response to Neoadjuvant Chemotherapy in Breast Cancer Patients

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• 作者：Hiroyo Takahashi ; Naofumi Kagara ; ^{kagaran@onsurg.med.osaka-u.ac.jp} ; Tomonori Tanei ; Yasuto Naoi ; Masafumi Shimoda ; Atsushi Shimomura ; Kenzo Shimazu ; Seung Jin Kim ; Shinzaburo Noguchi
• 关键词：Diagnostic marker ; OS-MSP ; Predictive marker ; RASSF1A methylation ; Tumor burden
• 刊名：Clinical Breast Cancer
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：17
• 期：1
• 页码：61-69.e3
• 全文大小：707 K
• 卷排序：17

文摘

Circulating tumor DNA (ctDNA) is known to harbor tumor-specific genetic or epigenetic alterations. In the present study, the correlation of ctDNA with tumor response to neoadjuvant chemotherapy (NAC) was evaluated in primary breast cancer patients.Patients and MethodsPlasma samples were obtained from 87 primary breast cancer patients (stage II-III) before and after NAC, as well as 1 year after surgery. Methylated ctDNA (met-ctDNA) was determined by one-step methylation-specific PCR (OS-MSP) for the promoter region of RASSF1A.ResultsThe positivity (23.0%, 20/87) of met-ctDNA before NAC was significantly (P < .05) higher than that of carcinoembryonic antigen (CEA) (8.6%) and cancer-associated antigen (CA) 15-3 (7.4%). In the patients with positive met-ctDNA before NAC, met-ctDNA significantly decreased after NAC in those with disease that responded to therapy (P = .006), but not in patients whose disease did not respond to therapy. Met-ctDNA after NAC was found to be significantly (P = .008) correlated to the extent of residual tumor burden. Of the 7 patients who showed an increase in met-ctDNA at 1 year after surgery, 3 developed recurrence.ConclusionMet-ctDNA is a more sensitive marker than CEA and CA15-3, and it might be useful in monitoring the clinical tumor response to NAC. In addition, the potential use of met-ctDNA as a tumor marker for monitoring postoperative recurrence has been suggested.