Matrix Metalloproteinase-9 as Prognostic Factor for the Treatment of HER-2 Enriched Breast Cancer

Abstract

Background: MMP-9 plays a significant role in invasion and migration of tumor cells and metastasis. A combination MMP-9 biomarker with HER2 and Ki-67 is expected to provide more specificity in prognosis for better breast cancer (BC) treatment options. Methods: A retrospective cohort of 34 patients with HER2 enriched breast cancer were studied from January 2016 until December 2020. Assessment MMP-9 by IHC using Monoclonal Mouse Anti-Human MMP-9 Antigen with semiquantitative immunoreactive scores methods was done. Results: The samples included patients aged 29 to 66 years. Patients' educational level was mostly high school graduation (n=17; 50%). Distant metastases occurred in 10 (29.4%) patients, histopathological Grade II was found in 29 (85.7%) patients, positive LVI was found in 18 (52.9%) patients, and high proliferation rate (Ki67 > 20%) was found in 32 (94.1%) patients. All the patients underwent MRM with a history of chemotherapy in 29 (85.3%) patients, radiotherapy in 14 (41.2%) patients, and targeted therapy in only seven (20.6%) patients. Most of the patients had locally advanced stage III (n=21; 61.8%). The MMP-9 High expression was found in 20 (58.8%) patients and 14 (41.2%) patients had a low expression. A significant relationship was found between MMP-9 expression and DFS (p=0.023); while a significant relationship was found with OS (p=0.093). The mean DFS for High expression MMP-9 was 37.3 months and 45.3 months for low expression. The mean OS was 37.6 months for High-intensity MMP-9 and 42.7 months for Low-intensity. Conclusions: The MMP-9 expression (p=0.037), age group<40 years old (p=0.024), and the history of radiotherapy (p=0.035) were significantly related to he occurrence of distant metastases. The MMP-9 High expression had a 7.5 times greater risk of distant metastases. Impacts: The MMP-9 can be used as a prognostic factor for distant metastasis in HER2 Enriched BC.