title: Prognostic discrimination using a 70-gene signature among patients with estrogen receptor-positive breast cancer and an intermediate 21-gene recurrence score.
abstract: The Oncotype DX® recurrence score (RS) predictor has been clinically utilized to appropriately select adjuvant chemotherapy for patients with estrogen receptor (ER)-positive early breast cancer. However, the selection of chemotherapy for patients with intermediate RSs remains controversial. We assessed the prognostic value of a 70-gene signature (70GS) among patients with ER-positive breast cancer and intermediate RSs. In addition, we sought to identify genes associated with poor 70GS scores based on gene expression profiling (GEP). GEP was performed using gene expression data from 186 patients with ER-positive breast cancer. The RS and 70GS score were calculated on the basis of GEP. Among 186 patients, 82 ER-positive patients with intermediate RSs were identified. These patients were stratified by 70GS, overall survival (OS) significantly differed according to 70GS (p=0.013). In a supervised hierarchical analysis according to 70GS, the expression of several representative genes for cell proliferation was significantly higher in the poor 70GS cluster than in the good 70GS cluster. Furthermore, among these patients, FOXM1, AURKA, AURKB, and BIRC5 displayed prognostic significance for OS. In conclusion, 70GS can help to discriminate survival differences among ER-positive patients with intermediate RSs. FOXM1, AURKA, AURKB, and BIRC5, are associated with poor 70GS scores.
authors.affiliation: Department of Surgery, Gananam Severance Hospital, Yonsei University College of Medicine, Seoul 135720, Korea. gsjjoon@yuhs.ac.
authors.forename: Sung Gwe
authors.initials: SG
authors.lastname: Ahn
authors.forename: Hak Min
authors.initials: HM
authors.lastname: Lee
authors.forename: Hak Woo
authors.initials: HW
authors.lastname: Lee
authors.forename: Seung Ah
authors.initials: SA
authors.lastname: Lee
authors.forename: Se-Ra
authors.initials: SR
authors.lastname: Lee
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Leem
authors.forename: Joon
authors.initials: J
authors.lastname: Jeong
authors.forename: In-Sun
authors.initials: IS
authors.lastname: Chu
mesh_terms: D000328:Adult; D000368:Aged; D064127:Aurora Kinases / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D016000:Cluster Analysis; D005260:Female; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011237:Predictive Value of Tests; D011379:Prognosis; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D000077022:Survivin; D055815:Young Adult
chemical_list: C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D051034:Inhibitor of Apoptosis Proteins; D011960:Receptors, Estrogen; D000077022:Survivin; D064127:Aurora Kinases