Twenty-year results of the Naples GUN randomized trial: predictive factors of adjuvant tamoxifen efficacy in early breast cancer

Clin Cancer Res. 2003 Mar;9(3):1039-46.

Abstract

Purpose: Tamoxifen (TAM) is increasingly administered to new early breast cancer patients. Because it is not devoid of toxic effects, we studied factors potentially predictive of its efficacy.

Experimental design: From 1978 to 1983, 433 patients were enrolled in the GUN randomized trial: 206 were assigned to TAM versus 227 controls (no-TAM). Premenopausal patients with axillary lymph node involvement (60 TAM versus 65 no-TAM) also received nine CMF cycles. Eight biological markers were retrospectively assayed for most patients: estrogen; progesterone; prolactin receptors (PrlRs); microvessel count (MVC); S-phase fraction; tumor ploidy; epidermal growth factor receptor (EGFR); and HER2. We performed a multivariate test of the TAM/covariate interactions to establish whether these variables predicted for TAM efficacy. Estimates of the TAM effect were expressed as hazard ratio (HR) of death of TAM over no-TAM patients with 95% confidence intervals (95% CIs).

Results: At a median follow-up of 15 years, PrlRs, MVC, S-phase fraction, ploidy, and EGFR did not influence TAM efficacy. Differently, HER2 had an overall significant predictive effect: HR = 0.59 (95% CI: 0.40-0.87) in HER2-negative subjects versus HR = 1.09 (95% CI: 0.63-1.87) in HER2-positive subjects (interaction test: P = 0.04). The predictive effect of HER2 was also evident in the subgroup of patients with steroid receptor-positive tumors (HER2 positive: HR = 1.33, 95% CI: 0.70-2.51; HER2 negative: HR = 0.73, 95% CI: 0.47-1.14).

Conclusions: With the statistical power of the present randomized trial, S-phase, ploidy, EGFR, PrlR, and MVC do not seem to predict for TAM efficacy. Conversely, our data support the hypothesis that tumors overexpressing HER2 might not benefit from adjuvant TAM.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Biomarkers, Tumor
  • Breast Neoplasms / drug therapy*
  • Chemotherapy, Adjuvant*
  • Clinical Trials as Topic
  • ErbB Receptors / biosynthesis
  • Female
  • Humans
  • Lymphatic Metastasis
  • Microcirculation
  • Middle Aged
  • Neovascularization, Pathologic
  • Ploidies
  • Proportional Hazards Models
  • Receptor, ErbB-2 / biosynthesis
  • Receptors, Prolactin / biosynthesis
  • S Phase
  • Tamoxifen / therapeutic use*
  • Time Factors

Substances

  • Biomarkers, Tumor
  • Receptors, Prolactin
  • Tamoxifen
  • ErbB Receptors
  • Receptor, ErbB-2