title: Rapid Changes in Circulating Tumor DNA in Serially Sampled Plasma During Treatment of Breast Cancer: A Case Report.
abstract: BACKGROUND The analysis of circulating tumor DNA (ctDNA) is expected to be a modality to determine the status of cancer in real time. This case indicated utilities and issues in measuring the ctDNA in cancer patients. CASE REPORT A 45-year-old woman with metastatic breast cancer was treated with bevacizumab and paclitaxel. The lung metastases were decreased but the meningitis carcinoma developed rapidly and she died. During the treatment with bevacizumab and paclitaxel, blood samples were taken serially and ctDNA was analyzed using a next-generation sequencer. TP53 frameshift mutation (TP53; p.Arg158fs with 7 nucleotides deletion) was identified in the tumor, and dynamic change in this mutation in ctDNA was observed in serially sampled plasma in this patient. We observed a rapid decrease of TP53 mutation at the beginning of treatment, then it increased as a sign of relapse. However, the high allelic fraction value of TP53 mutation was not consistent during the progression of cancer, suggesting that several factors affected the value of ctDNA. CONCLUSIONS Although this is a single-case experience, it strongly suggests ctDNA could be a modality to determine the cancer status in real time. However, we found that several factors affected the value of ctDNA. Further investigations are needed to reveal the significance of these very high-sensitivity changes.
authors.affiliation: Department of Surgery, Yamanashi Prefectural Central Hospital, Kofu, Yamanashi, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakagomi
authors.affiliation: Genome Analysis Center, Yamanashi Prefectural Central Hospital, Kofu, Yamanashi, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Hirotsu
authors.affiliation: Genome Analysis Center, Yamanashi Prefectural Central Hospital, Kofu, Yamanashi, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Amemiya
authors.affiliation: Department of Surgery, Yamanashi Prefectural Central Hospital, Kofu, Yamanashi, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Nakada
authors.affiliation: Department of Surgery, Yamanashi Prefectural Central Hospital, Kofu, Yamanashi, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Inoue
authors.affiliation: Genome Analysis Center, Yamanashi Prefectural Central Hospital, Kofu, Yamanashi, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Mochizuki
authors.affiliation: Department of Pathology, Yamanashi Prefectural Central Hospital, Kofu, Yamanashi, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Oyama
authors.affiliation: Genome Analysis Center, Yamanashi Prefectural Central Hospital, Kofu, Yamanashi, Japan.|University of Tokyo, Tokyo, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Omata
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D002277:Carcinoma / Q000235:genetics* / Q000556:secondary / Q000628:therapy; D004273:DNA, Neoplasm / Q000097:blood*; D017809:Fatal Outcome; D005260:Female; D016368:Frameshift Mutation; D016158:Genes, p53; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000556:secondary / Q000628:therapy; D008577:Meningeal Neoplasms / Q000235:genetics* / Q000556:secondary / Q000628:therapy; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D018714:Radiotherapy, Adjuvant / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D000068258:Bevacizumab; D017239:Paclitaxel