title: A seven-gene signature can predict distant recurrence in patients with triple-negative breast cancers who receive adjuvant chemotherapy following surgery.
abstract: The aim of this study was to investigate candidate genes that might function as biomarkers to differentiate triple negative breast cancers (TNBCs) among patients, who received adjuvant chemotherapy after curative surgery. We tested whether the results of a NanoString expression assay that targeted 250 prospectively selected genes and used mRNA extracted from formalin-fixed, paraffin-embedded would predict distant recurrence in patients with TNBC. The levels of expression of seven genes were used in a prospectively defined algorithm to allocate each patient to a risk group (low or high). NanoString expression profiles were obtained for 203 tumor tissue blocks. Increased expressions of the five genes (SMAD2, HRAS, KRT6A, TP63 and ETV6) and decreased expression of the two genes (NFKB1 and MDM4) were associated favorable prognosis and were validated with cross-validation. The Kaplan-Meier estimates of the rates of distant recurrence at 10 years in the low- and high-risk groups according to gene expression signature were 62% [95% confidence interval (CI), 48.6-78.9%] and 85% (95% CI, 79.2-90.7%), respectively. When adjusting for TNM stage, the distant recurrence-free survival (DRFS)s in the low-risk group was significantly longer than that in the high-risk group (p <0.001) for early stage (I and II) and advanced stage (III) tumors. In a multivariate Cox regression model, the gene expression signature provided significant predictive power jointly with the TNM staging system. A seven-gene signature could be used as a prognostic model to predict DRFS in patients with TNBC who received curative surgery followed by adjuvant chemotherapy.
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
authors.forename: Hae Hyun
authors.initials: HH
authors.lastname: Jung
authors.forename: In-Gu
authors.initials: IG
authors.lastname: Do
authors.forename: Eun Yoon
authors.initials: EY
authors.lastname: Cho
authors.forename: Insuk
authors.initials: I
authors.lastname: Sohn
authors.forename: Sin-Ho
authors.initials: SH
authors.lastname: Jung
authors.forename: Won Ho
authors.initials: WH
authors.lastname: Kil
authors.forename: Seok Won
authors.initials: SW
authors.lastname: Kim
authors.forename: Jeong Eon
authors.initials: JE
authors.lastname: Lee
authors.forename: Seok Jin
authors.initials: SJ
authors.lastname: Nam
authors.forename: Jin Seok
authors.initials: JS
authors.lastname: Ahn
authors.forename: Young-Hyuck
authors.initials: YH
authors.lastname: Im
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D017024:Chemotherapy, Adjuvant / Q000379:methods; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology*; D009367:Neoplasm Staging / Q000379:methods; D011379:Prognosis; D059467:Transcriptome / Q000235:genetics*; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology* / Q000601:surgery
chemical_list: D014408:Biomarkers, Tumor
keywords: chemotherapy; expression assay; prognostic factor; triple negative breast cancer