Abstract

Breast cancer is by far the most common cancer in women worldwide and the main cause of cancer-related mortality. Breast cancer accounts for 38% of all malignancies among Egyptian women. The aim of our study was to evaluate the serum levels of human epidermal growth factor receptor-2 (HER2), matrix metalloproteinase-9 (MMP-9), nitric oxide (NO), and total antioxidant capacity (TAC) in breast cancer patients and to correlate these markers with clinico-pathological parameters. Serum HER2, MMP-9, and carcinoma antigen 15-3 (CA 15-3) were assessed in 80 breast cancer patients and ten healthy subjects as a control group by the enzyme-linked immunosorbent assay (ELISA) technique while NO and TAC were assessed by a colorimetric method. Serum HER2 was ≥15 ng/mL in nine patients (11.3%). High HER2 ECD levels were significantly associated with tissue HER2 (P<0.0001), metastasis (P= 0.0024), and negativity of both estrogen (P=0.0075) and progesterone (P=0.0239) receptors. Serum MMP-9 (P=0.0013), NO (P<0.0001), and CA 15-3 (P<0.0001) were significantly increased while serum TAC was significantly (P=0.01) decreased in breast cancer patients as compared to the control group. Serum MMP-9 was increased significantly (P=0.028) in metastatic patients as compared to non-metastatic patients. We found a positive correlation between serum HER2 and CA 15-3 (r=36, p=0.005). In conclusion, serum HER2 reflects the tissue HER2 status of breast cancer, so the determination of serum HER2 is helpful in assessing HER2 status, but in addition, a high level may reflect metastatic disease. Also, serum MMP-9 can be useful for denoting the development of metastasis in breast cancer patients. Follow-up is needed to evaluate the value of serum HER2 and MMP-9 as prognostic markers.

Highlights

  • Breast cancer is by far the most common cancer in women worldwide and the main cause of cancer-related mortality [1]

  • Serum human epidermal growth factor receptor-2 (HER2) reflects the tissue HER2 status of breast cancer, so the determination of serum HER2 is helpful in the assessment of the HER2 status, but in addition a high level may reflect metastatic disease

  • Serum matrix metalloproteinase-9 (MMP-9) can be useful for denoting the development of metastasis in breast cancer patients

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Summary

Introduction

Breast cancer is by far the most common cancer in women worldwide and the main cause of cancer-related mortality [1]. In Egypt, as in many other parts of the world, breast cancer is the most common type of cancer: it accounts for approximately 38% of reported malignancies among Egyptian women [2]. The human epidermal growth factor receptor (HER)-2 (HER2/neu, c-erbB-2) is a transmembrane receptor that is overexpressed in 15–25% of breast cancers. HER2 overactivity is associated with adverse biological characteristics and poor clinical outcomes. It is an attractive target for therapeutic intervention, a strategy that has been clinically validated [3]. The serum extracellular domain fragment of HER2 (HER2 ECD) represents a non-invasive and quantifiable biomarker that could supplement existing HER2/neu testing [6]

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