title: Twenty-year results of the Naples GUN randomized trial: predictive factors of adjuvant tamoxifen efficacy in early breast cancer.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Cattedra di Oncologia Medica, Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Università Federico II, Via Sergio Pansini 5, 80131 Naples, Italy.
authors.forename: Sabino
authors.initials: S
authors.lastname: De Placido
authors.forename: Michelino
authors.initials: M
authors.lastname: De Laurentiis
authors.forename: Chiara
authors.initials: C
authors.lastname: Carlomagno
authors.forename: Ciro
authors.initials: C
authors.lastname: Gallo
authors.forename: Franco
authors.initials: F
authors.lastname: Perrone
authors.forename: Stefano
authors.initials: S
authors.lastname: Pepe
authors.forename: Angela
authors.initials: A
authors.lastname: Ruggiero
authors.forename: Alfredo
authors.initials: A
authors.lastname: Marinelli
authors.forename: Clorindo
authors.initials: C
authors.lastname: Pagliarulo
authors.forename: Luigi
authors.initials: L
authors.lastname: Panico
authors.forename: Guido
authors.initials: G
authors.lastname: Pettinato
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Petrella
authors.forename: Angelo Raffaele
authors.initials: AR
authors.lastname: Bianco
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D002986:Clinical Trials as Topic; D066246:ErbB Receptors / Q000096:biosynthesis; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008833:Microcirculation; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D011003:Ploidies; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D011981:Receptors, Prolactin / Q000096:biosynthesis; D016196:S Phase; D013629:Tamoxifen / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D011981:Receptors, Prolactin; D013629:Tamoxifen