title: c-myc amplification is a better prognostic factor than HER2/neu amplification in primary breast cancer.
abstract: Amplification of the c-myc and HER2/neu genes was found in 20 and 23%, respectively, of primary breast cancer tissues derived from 282 patients (median follow-up, 74 months). c-myc amplification was observed more frequently in larger tumors (P = 0.01) and in lymph node-positive patients (P = 0.01) but was not associated with age, menopausal status, or with differentiation grade or steroid receptor status. c-myc amplification was strongly negatively correlated with HER2/neu amplification (P less than 0.001). In univariate analysis, amplification of c-myc proved to be a significant predictor of reduced relapse-free and overall survival (for both, P less than 0.001). In multivariate analysis for relapse-free survival, c-myc amplification significantly (P = 0.001) added to the prognostic power of tumor size (P less than 0.001), lymph node status (P less than 0.001), and estrogen receptor status (P = 0.003), with the highest relative failure rate (1.8) after lymph node status (2.2). In this pilot study, c-myc amplification was predictive for outcome, especially among patients with node-negative disease or steroid receptor-positive tumors; 51 and 46% differences in actuarial 5-year recurrence rates when compared to patients with tumors with normal c-myc gene copy numbers, respectively. HER2/neu amplification was not associated with relapse-free survival but weakly with shorter overall survival in univariate analysis (P = 0.035). Only in the relatively small subgroup of steroid receptor-negative tumors, HER2/neu amplification may identify those patients with an increased risk of death. In conclusion, amplification of c-myc is an independent powerful prognosticator, particularly in node-negative and steroid receptor-positive breast cancer, whereas HER2/neu amplification may be of limited prognostic value, only in steroid receptor-negative disease.
authors.affiliation: Division of Endocrine Oncology (Department of Medical Oncology), Dr. Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
authors.forename: E M
authors.initials: EM
authors.lastname: Berns
authors.forename: J G
authors.initials: JG
authors.lastname: Klijn
authors.forename: W L
authors.initials: WL
authors.lastname: van Putten
authors.forename: I L
authors.initials: IL
authors.lastname: van Staveren
authors.forename: H
authors.initials: H
authors.lastname: Portengen
authors.forename: J A
authors.initials: JA
authors.lastname: Foekens
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality; D005260:Female; D005784:Gene Amplification / Q000235:genetics*; D016259:Genes, myc / Q000235:genetics; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D011519:Proto-Oncogenes / Q000235:genetics*; D016019:Survival Analysis