Impact of Adjuvant Treatment on Heparanase Concentration in Invasive, Unilateral Breast Cancer Patients: Results of a Prospective Single-Centre Cohort Study

Abstract

Background: In recent years, great progress has been made in the treatment of breast cancer, but it is still one of the ten leading causes of death in women. The aim of the study was to evaluate the heparanase concentration of invasive breast cancer (IBrC) patients, before and after cancer adjuvant treatment. Methods: Eighty patients with stage IA to IIB IBrC receiving adjuvant treatment were included prospectively in this study. The heparanase concentrations were determined by an enzyme-linked immunosorbent assay. A univariate analysis was used to estimate the factors influencing the low or high pre-treatment concentration of heparanase and the low or high numerical decrease in heparanase concentration after completion of adjuvant treatment. Results: Treatment reduced the concentration of heparanase by almost four times in the general IBrC cohort. Higher levels of pre- and post-treatment heparanase were noted in oestrogen receptor-negative cancers than in positive ones. A higher post-treatment concentration of heparanase was found in patients with a triple-negative tumour compared to patients with a luminal B HER2 negative type of IBrC. Overweight IBrC subjects and those with a tumour diameter of ≥2 cm demonstrated a lower chance of a lower pre-treatment heparanase concentration. Interestingly, a pre-treatment heparanase concentration is the main predictor of the changes in heparanase concentration after adjuvant treatment. Follow-up revealed significantly lower progression-free survival (PFS) rates in IBrC patients with a pre-treatment concentration of heparanase higher than 181.46 pg/mL (PFS = 80%). Conclusions: Our findings provide supporting evidence that IBrC therapy reduced the heparanase levels, regardless of treatment patterns and a pre-treatment concentration of heparanase may serve as a prognostic indicator for future outcomes.

The HPSE Gene Insulator—A Novel Regulatory Element That Affects Heparanase Expression, Stem Cell Mobilization, and the Risk of Acute Graft versus Host Disease

“…Heparanase is known to play a decisive role in tumor metastasis and angiogenesis [5]. High expression of heparanase is frequently observed in a long list of primary human tumors of various etiologies, in correlation with high vessel density and a poor clinical outcome [40][41][42][43]. The enzyme is also involved in inflammation [44], fibrosis [45], diabetes [46], and kidney dysfunction [47].…”