Association between plasma MMP-9 activity and the outcome of breast cancer patients.

SM Ranuncolo MD, E Armanasco MD, C Cresta MD, EDBK Joffe MD PhD and LI Puricelli PhD.

Research Area, Institute of Oncology "Angel H. Roffo", Buenos Aires, Buenos Aires Argentina

In a previous work, we found that MMP-9 activity was significantly elevated in the euglobulin plasma fraction of breast cancer patients as compared with benign breast pathologies and healthy controls. Aim: to determine whether there is an association between circulating MMP-9 activity and the outcome of individual patients. Methods: we studied the enzyme activity by gelatin quantitative zymography. The blood samples were taken before surgery (sample (S) 1), one month after (S2), and every three months (S3 and the following ones). Results: in 39 S2 we found a decreased in the 63% of the patients, independently of the level recorded in S1. MMP-9 circulating activity was determined in 46 patients during the adjuvant treatment, 24 patients received monomodality therapy and 22 combined one (S3-S5). In 44 patients with no evidence of disease, MMP-9 levels decreased as compared with the S1, while 2 patients showed and enhancement in correlation with their illness progression, independently of the sort of therapy received. Further analysis, once adjuvant treatment was over (S6-S20, follow-up period), indicated that in all patients who never showed evidence of recurrent pathology and are disease-free, MMP-9 remained low respect to the MMP-9 value recorded in S1, while in 9 patients who developed progressive disease during or after adjuvant treatment, showed enhanced MMP-9 plasma activity, 1 to 8 months preceding the clinical detection of pathology progression. We have another group of 14 patients, from which 10, came into the follow-up protocol free of illness and they have low levels of MMP-9, while in 4 we determined high values in correlation with progressive disease. Conclusions: MMP-9 plasma activity would be a useful marker to monitor the response of breast cancer patients to their primary and adjuvant treatments. It would also represent a novel clinical tool for the follow up of breast cancer patients and the detection of recurrent tumors earlier than known current clinical and molecular parameters.

KEY WORDS: MMP-9 plasma activity, circulating MMP-9, breast cancer, adjuvant therapy, follow-up period.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Risk Assessment, Part 1.