title: Correlation of Methylated Circulating Tumor DNA With Response to Neoadjuvant Chemotherapy in Breast Cancer Patients.
abstract: 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.
  
  
  
  Plasma 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.
  
  
  
  The 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.
  
  
  
  Met-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.
authors.affiliation: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Hiroyo
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan. Electronic address: kagaran@onsurg.med.osaka-u.ac.jp.
authors.forename: Naofumi
authors.initials: N
authors.lastname: Kagara
authors.affiliation: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Tanei
authors.affiliation: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Naoi
authors.affiliation: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Shimoda
authors.affiliation: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shimomura
authors.affiliation: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Kenzo
authors.initials: K
authors.lastname: Shimazu
authors.affiliation: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Seung Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Shinzaburo
authors.initials: S
authors.lastname: Noguchi
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D015996:Survival Rate
chemical_list: D004273:DNA, Neoplasm
keywords: Diagnostic marker; OS-MSP; Predictive marker; RASSF1A methylation; Tumor burden