Oncogene amplification and prognosis in breast cancer: relationship with systemic treatment

Gene. 1995 Jun 14;159(1):11-8. doi: 10.1016/0378-1119(94)00534-y.

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)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Cyclophosphamide / therapeutic use
  • Female
  • Fibroblast Growth Factor 3
  • Fibroblast Growth Factors / genetics
  • Fluorouracil / therapeutic use
  • Gene Amplification*
  • Genetic Markers
  • Humans
  • Methotrexate / therapeutic use
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local
  • Oncogenes / genetics*
  • Progestins / therapeutic use
  • Prognosis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-myc / genetics
  • Receptor, ErbB-2 / genetics
  • Risk Factors
  • Survival Rate
  • Tamoxifen / therapeutic use
  • Treatment Outcome

Substances

  • FGF3 protein, human
  • Fibroblast Growth Factor 3
  • Genetic Markers
  • Progestins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-myc
  • Tamoxifen
  • Fibroblast Growth Factors
  • Cyclophosphamide
  • Receptor, ErbB-2
  • Fluorouracil
  • Methotrexate

Supplementary concepts

  • CMF regimen