Worse prognosis in breast cancer patients can be predicted by immunohistochemical analysis of positive MMP-2 and negative estrogen and progesterone receptors.

Introduction:: Breast cancer is the most cause of death, and approximately 90% of these deaths are due to metastases. Matrix metalloproteinase-2 (MMP-2) gelatinase activity is able to degrade a major constituent of the tumor microenvironment, type IV collagen. Two well-established proteins used as markers in clinical practice for breast cancer are the receptors for estrogen (ER) and progesterone (PR). Although the presence of these receptors has been associated with a better prognosis, loss of these proteins can occur during tumor progression, with subsequent resistance to hormone therapy.

Objective:: To study the correlation among MMP-2, ER, and PR, as well as the establishment of the metastatic process in primary breast tumors.

Method:: Breast cancer samples (n=44) were analyzed by immunohistochemistry for MMP-2, ER, and PR.

Results:: We observed that 90% of patients who had metastases and died showed positive staining for MMP-2 (p=0.0082 for both). Using Kaplan-Meier analysis, we found that negative ER patients who were also positive for MMP-2 had even worse disease-free survival (DFS) and overall survival (OS) (p= 0.012 and p=0.005, respectively). Similar results were found in PR-negative patients for DFS (a trend p=0.077) and OS (p=0.038).

Conclusion:: Regardless of our small sample size (n=44), the data obtained strongly suggest that MMP-2 in combination with already well-established markers could help to predict the emergence of metastases and death in patients with breast cancer.