Change of influence of prognostic markers on metastasis free interval during and after adjuvant tamoxifen therapy in breast cancer patients.

PURPOSE: To evaluate the influence of molecular biomarkers (estrogen receptor - ER, progesterone receptor - PR, and human epidermal growth factor receptor2 - HER2) and pathological parameters on metastasis free interval (MFI) in adjuvantly tamoxifen-treated breast cancer patients, during different follow up periods (0-2.5 years, 2.5-5 years and 5-12 years). METHODS: The study included 113 postmenopausal breast cancer patients with known pathological parameters. Steroid receptors were determined by ligand-binding assay and HER2 amplification status by chromogenic in situ hybridization (CISH). RESULTS: During the first 2.5 years of therapy patients with ER <5 fmol/mg, PR <5 fmol/mg or pT2 (≥2cm) tumors had higher probability of distant metastasis. For the period between 2.5-5 years, analysis of MFI according to pathological parameters and molecular biomarkers, separately, did not show any statistically significant difference. Patients with pT≥2 cm and HER2 amplification had much greater chance of developing distant metastasis when compared to other phenotypes (HER2-negative/pT1, HER2-negative/pT2 and HER2-positive/pT1). Patiens with ER ≥160 fmol/mg and PR ≥45 fmol/mg had good prognosis after 5 years of tamoxifen therapy. CONCLUSION: Our study indicates that there is a change of influence of the analyzed pathological parameters on MFI, depending on different follow up periods. Steroid receptor status, tumor size and HER2 status (alone or in combination) are significant parameters for the course of disease of postmenopausal ER-positive breast cancer patients, but during different periods of follow up.