title: Oncogene amplification and prognosis in breast cancer: relationship with systemic treatment.
abstract: In the present study, we aimed to clarify the potential of oncogene amplifications as markers for the prediction of (i) (relapse-free) survival, (ii) response to first-line endocrine therapy and (iii) subsequent chemotherapy in patients with recurrent breast cancer. To attain this goal, amplification of different oncogenes (HER-2/neu, c-MYC and INT-2) was studied in primary tumors of a series of 259 patients with breast cancer (median follow-up of 72 mo). Of these tumors, 49.8% did not contain an amplification of any of the oncogenes studied, whereas in the amplified subgroup, INT-2 was amplified in 13%, HER-2/neu in 24% and c-MYC in 20% of the tumors. In univariate analysis, INT-2 amplification was associated with an increased risk of relapse (p < 0.03), especially in the subgroups of 85 node-negative (p = 0.05) and 156 ER/PgR-positive patients (p = 0.01). Cox multivariate regression analysis showed that c-MYC was the only oncogene whose amplification was significantly related with the rate of relapse. With respect to amplification in patients developing metastatic disease, who received first-line hormonal therapy (n = 114), HER-2/neu amplification was associated with a less favorable response to endocrine therapy (objective response rate only 17% and a progression-free survival (PFS) of only 4% at 12 mo). Interestingly, distinct INT-2 amplification might predict a better response to endocrine therapy (objective response rate of 56%, and a PFS after relapse of 42% at 12 mo).(ABSTRACT TRUNCATED AT 250 WORDS)
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 A
authors.initials: JA
authors.lastname: Foekens
authors.forename: I L
authors.initials: IL
authors.lastname: van Staveren
authors.forename: W L
authors.initials: WL
authors.lastname: van Putten
authors.forename: H Y
authors.initials: HY
authors.lastname: de Koning
authors.forename: H
authors.initials: H
authors.lastname: Portengen
authors.forename: J G
authors.initials: JG
authors.lastname: Klijn
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D051518:Fibroblast Growth Factor 3; D005346:Fibroblast Growth Factors / Q000235:genetics; D005472:Fluorouracil / Q000627:therapeutic use; D005784:Gene Amplification; D005819:Genetic Markers; D006801:Humans; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009857:Oncogenes / Q000235:genetics*; D011372:Progestins / Q000627:therapeutic use; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D012307:Risk Factors; D015996:Survival Rate; D013629:Tamoxifen / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D003520:Cyclophosphamide; D051518:Fibroblast Growth Factor 3; D005346:Fibroblast Growth Factors; D005472:Fluorouracil; D005819:Genetic Markers; D008727:Methotrexate; D011372:Progestins; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D018719:Erb-b2 Receptor Tyrosine Kinases; D013629:Tamoxifen; C496444:FGF3 protein, human