title: Relationship between quantitative GRB7 RNA expression and recurrence after adjuvant anthracycline chemotherapy in triple-negative breast cancer.
abstract: OBJECTIVE
  To conduct an exploratory analysis of the relationship between gene expression and recurrence in patients with operable triple-negative breast cancer (TNBC) treated with adjuvant doxorubicin-containing chemotherapy.
  
  
  METHODS
  RNA was extracted from archived tumor samples derived from 246 patients with stage I-III TNBC treated with adjuvant doxorubicin-containing chemotherapy, and was analyzed by quantitative reverse transcriptase PCR for a panel of 374 genes. The relationship between gene expression and recurrence was evaluated using weighted Cox proportional hazards model score tests.
  
  
  RESULTS
  Growth factor receptor bound protein 7 (GRB7) was the only gene for which higher expression was significantly associated with increased recurrence in TNBC (Korn's adjusted P value = 0.04). In a Cox proportional hazards model adjusted for clinicopathologic features, higher GRB7 expression was associated with an increased recurrence risk (HR = 2.31; P = 0.04 using the median as the split). The 5-year recurrence rates were 10.5% [95% confidence intervals (CI), 7.8-14.1] in the low and 20.4% (95% CI, 16.5-25.0) in the high GRB7 groups. External validation in other datasets indicated that GRB7 expression was not prognostic in two adjuvant trials including variable systemic therapy, but in two other trials showed that high GBR7 expression was associated with resistance to neoadjuvant doxorubicin and taxane therapy.
  
  
  CONCLUSIONS
  GRB7 was associated with an increased risk of recurrence in TNBC, suggesting that GRB7 or GRB7-dependent pathways may serve as potential biomarkers for therapeutic targets. Therapeutic targeting of one or more factors identified which function as interaction nodes or effectors should also be considered.
authors.affiliation: Albert Einstein College of Medicine, Bronx, New York 10461, USA. jsparano@montefiore.org
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Sparano
authors.forename: Lori J
authors.initials: LJ
authors.lastname: Goldstein
authors.forename: Barrett H
authors.initials: BH
authors.lastname: Childs
authors.forename: Steven
authors.initials: S
authors.lastname: Shak
authors.forename: Diana
authors.initials: D
authors.lastname: Brassard
authors.forename: Sunil
authors.initials: S
authors.lastname: Badve
authors.forename: Frederick L
authors.initials: FL
authors.lastname: Baehner
authors.forename: Roberto
authors.initials: R
authors.lastname: Bugarini
authors.forename: Steve
authors.initials: S
authors.lastname: Rowley
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
authors.forename: Lawrence N
authors.initials: LN
authors.lastname: Shulman
authors.forename: Silvana
authors.initials: S
authors.lastname: Martino
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Davidson
authors.forename: Paraic A
authors.initials: PA
authors.lastname: Kenny
authors.forename: George W
authors.initials: GW
authors.lastname: Sledge
authors.forename: Robert
authors.initials: R
authors.lastname: Gray
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D017024:Chemotherapy, Adjuvant; D004317:Doxorubicin / Q000008:administration & dosage*; D005260:Female; D051382:GRB7 Adaptor Protein / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012008:Recurrence
chemical_list: D014408:Biomarkers, Tumor; D004317:Doxorubicin; D051382:GRB7 Adaptor Protein; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone