title: GRB7 protein over-expression and clinical outcome in breast cancer.
abstract: The growth factor receptor-bound protein-7 gene (GRB7) encodes a multi-domain signal transduction molecule. The purpose of this study was to examine the clinical significance of GRB7 protein expression in human breast cancer. Western blotting analysis of protein extracts from 563 annotated frozen breast tumors was performed. Expression status of GRB7 and HER-2 was correlated with clinical covariates and outcomes. Cox proportional hazards were used to identify factors associated with breast cancer-free interval. The median follow-up was 71 months. P values <0.05 were considered statistically significant (two-sided). A discrepancy between HER-2 and GRB7 protein over-expression was observed. GRB7 protein over-expression was associated with negative estrogen and progesterone receptor status, higher tumor grade, larger primary tumor size, (more) axillary lymph node involvement, higher clinical stage, and shortened breast cancer-free interval. HER-2 protein over-expression was associated only with higher tumor grade. Multi-variate analysis revealed that GRB7 protein over-expression was an independent adverse prognostic factor for breast cancer-free interval (hazard ratio 1.69, 95% confidence interval 1.07-2.67; P = 0.024). The same was true of the subset of patients who did not receive any adjuvant systemic therapy (hazard ratio 1.68, 95% confidence interval 1.16-2.31; P = 0.0055). Using FISH analysis, 32/32 (100%; 95% CI 89-100%) tumors which over-expressed both HER-2 and GRB7 proteins and 1/35 (3%; 95% CI 0-15%) tumors with HER-2 but no GRB7 protein over-expression with Western blotting analysis demonstrated HER-2 gene amplification. GRB7 protein over-expression is an independent adverse prognostic factor in human breast cancer.
authors.affiliation: Department of Physiology and Pharmacology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
authors.forename: Betsy
authors.initials: B
authors.lastname: Ramsey
authors.forename: Tao
authors.initials: T
authors.lastname: Bai
authors.forename: Amy
authors.initials: A
authors.lastname: Hanlon Newell
authors.forename: Megan
authors.initials: M
authors.lastname: Troxell
authors.forename: Byung
authors.initials: B
authors.lastname: Park
authors.forename: Susan
authors.initials: S
authors.lastname: Olson
authors.forename: Edward
authors.initials: E
authors.lastname: Keenan
authors.forename: Shiuh-Wen
authors.initials: SW
authors.lastname: Luoh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D051382:GRB7 Adaptor Protein / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D051382:GRB7 Adaptor Protein; D018719:Erb-b2 Receptor Tyrosine Kinases; C495955:GRB7 protein, human; C508053:ERBB2 protein, human