Circulating MMP-9 and CYR61 Levels in HER2-Positive and -Negative Breast Cancer Subtypes

Breast cancer is the most commonly diagnosed cancer in women globally and a leading cause of cancer-related deaths. In Azerbaijan, breast cancer cases have steadily increased, with significant numbers recorded between 2020 and 2023. The human epidermal growth factor receptor 2 (HER2) gene is central in breast cancer pathology, particularly in aggressive forms with HER2 overexpression. However, emerging evidence shows that HER2 mutations may also occur in HER2-negative cases, potentially impacting prognosis and therapeutic outcomes. Aim: This study investigates HER2 gene expression and mutation status in HER2-negative breast cancer cases and analyzes circulating matrix proteins (MMP-7, MMP-9, CYR61) in different breast cancer subtypes. Methods: A total of 74 women aged 30–71 years with confirmed BC were enrolled. Patients were categorized as HER2-positive (n=33), HER2-negative (n=33), and triple-negative (n=8). HER2 mutation testing was conducted using AmoyDx kits via real-time PCR. Serum levels of MMP-7, MMP-9, and CYR61 were measured and statistically analyzed. Results: No HER2 mutations were found in HER2-negative patients, supporting prior research indicating the rarity of such mutations in these subtypes. MMP-9 was significantly reduced in all breast cancer groups (p<0.001), while CYR61 levels were markedly elevated, with an inverse correlation observed between MMP-9 and CYR61 (r = -0.314, p < 0.003). Conclusion: HER2 mutations are uncommon in HER2-negative breast cancers. Serum MMP-9 and CYR61 can serve as valuable diagnostic markers across BC subtypes. The findings support further exploration into alternative molecular targets beyond HER2 for effective treatment strategies.