title: Molecular characterization of patients with pathologic complete response or early failure after neoadjuvant chemotherapy for locally advanced breast cancer using next generation sequencing and nCounter assay.
abstract: Neoadjuvant chemotherapy (NAC) has the added advantage of increasing breast conservation rates with equivalent survival outcomes compared with adjuvant chemotherapy. A subset of breast cancer patients who received NAC experienced early failure (EF) during the course of therapy or within a short period after curative breast surgery. In contrast, patients with pathological complete response (pCR) were reported to have markedly favorable outcomes. This study was performed to identify actionable mutation(s) and to explain refractoriness and responsiveness to NAC. Included in this analysis were 76 patients among 397 with locally advanced breast cancer for whom a preoperative fresh-frozen paraffin-embedded tumor block was available for next-generation sequencing using AmpliSeq. The incidence of missense mutations in KRAS was much higher in patients with EF than in other groups (p < 0.01). In contrast, polymorphisms of the cMET gene were found in patients with pCR exclusively (p < 0.01).
authors.affiliation: Samsung Genomic Institute, Samsung Biological Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Kyunghee
authors.initials: K
authors.lastname: Park
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Moon Ki
authors.initials: MK
authors.lastname: Choi
authors.affiliation: Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hae Hyun
authors.initials: HH
authors.lastname: Jung
authors.affiliation: Center of Companion Diagnostics, Innovative Cancer Medicine Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: In-Gu
authors.initials: IG
authors.lastname: Do
authors.affiliation: Life Science Solutions Group, Thermo Fisher Scientific Corporation, Seoul, Korea.
authors.forename: Kwang Hee
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Samsung Genomic Institute, Samsung Biological Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: TaeJin
authors.initials: T
authors.lastname: Ahn
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Won Ho
authors.initials: WH
authors.lastname: Kil
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Seok Won
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jeong Eon
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Seok Jin
authors.initials: SJ
authors.lastname: Nam
authors.affiliation: Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Korea.
authors.forename: Duk-Hwan
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jin Seok
authors.initials: JS
authors.lastname: Ahn
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Young-Hyuck
authors.initials: YH
authors.lastname: Im
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Yeon Hee
authors.initials: YH
authors.lastname: Park
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001483:Base Sequence; D001940:Breast / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics; D020360:Neoadjuvant Therapy; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017211:Treatment Failure
chemical_list: C117307:KRAS protein, human; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D016283:Proto-Oncogene Proteins p21(ras)
keywords: breast cancer; neoadjvant chemotherapy; pathologic complete response; refractory