Epidermal growth factor receptor and S-phase fraction as prognosticator combination in node negative primary breast cancer

Despite the relatively good prognosis of node negative breast cancer (NNBC) it is necessary to determine prognostic factors to identify subgroups of high and low risk situation for recurrence and death. In 111 patients with primary NNBC we have examined the impact of two new prognosticators on disease-free intervall (DFI) and overall survival (OAS): S-phase fraction (SPF) as a proliferative marker (n = 107 P) and epidermal growth factor receptor (EGF-R) as a marker for differentiation (n = 62 P). Only fresh frozen tissue was used. SPF was detected by flow cytometry and EGF-R by a radioimmunoassay There was a strong correlation between grade III tumours and high SPF (>5%) (p < 0.001). However, grading was not related to EGF-R levels. No correlation between SPF and EGF-R to age and stage could be found. In log rank analysis patients with SPF >5% had a significant shorter DFI (p = 0.009) and OAS (p = 0.01) than with SPF <5%. Similar results were obtained for tumours with EGFR levels >15 fmol/mg (p = 0.07 resp. p = 0.05). However, in a Cox regression model only trends have been observed for independency of the new factors. Using a combination of both factors, a group of patients with good risk could be identified, if at least one factor was expressed favourably. If both factors were elevated, clinical outcome was poor (DFI: p < 0.004; OAS: p < 0.002). In further prospective trials the predictive value of the parameter combination should be investigated in adjuvant systemic therapy trials.