Matrix metalloproteinase-2 (MMP-2) is associated with the risk for a relapse in postmenopausal patients with node-positive breast carcinoma treated with antiestrogen adjuvant therapy.

Node-positive breast carcinoma is an aggressive disease. Postmenopausal patients benefit from antiestrogen adjuvant therapy. Predictive markers could, however, be useful in selecting these patients for different modalities of adjuvant therapy. Recently, we showed that MMP-2 (72 kD type IV collagenase/gelatinase A) is correlated with unfavorable prognosis in premenopausal breast carcinoma patients. Expression of the immunoreactive protein for MMP-2 was evaluated prospectively in this study in paraffin tissue sections from primary tumors of 100 postmenopausal, node-positive breast carcinoma patients treated with an adjuvant antiestrogen therapy. A specific MMP-2 monoclonal antibody in an avidin-biotin immunohistochemical staining was used. Sixty nine percent of the samples were MMP-2 positive. Eighty three percent of the MMP-2 negative patients lived for 5 years without a recurrence, while only 67% of the patients with an MMP-2 positive primary tumor were recurrence-free at that time (p < 0.05; log rank analysis). MMP-2 positivity showed a significant correlation with shortened survival in patients with a small primary tumor (T1-2) and a low axillary tumor burden. One hundred percent of these patients with an MMP-2 negative breast carcinoma survived for 5 years, compared to 73% of the MMP-2 positive cases alive at that time (p = 0.02). In conclusion, we show here that MMP-2 is a prognostic indicator in postmenopausal patients with node-positive breast carcinoma with a low tumor burden, and that it predicts a risk for failure in antiestrogen adjuvant therapy. It might have predictive value in selecting the most efficient adjuvant therapy in this set of patients.

High response rate with a lower dose of paclitaxel in combination with cisplatin in heavily pretreated patients with advanced breast carcinoma.

BACKGROUND: Paclitaxel has been found to be efficacious in the treatment of breast carcinoma either when administered alone or in combination with other anticancer agents. Synergistic interaction between paclitaxel and cisplatin has been demonstrated in vitro. METHODS: Thirty-two patients with breast carcinoma that was resistant to anthracyclines and to several other antineoplastic agents were selected to receive 80 mg/m(2) of paclitaxel on Day 1 and 80 mg/m(2) of cisplatin on Day 2 with a 3-week interval between the courses. RESULTS: High response rates were observed, with 3 complete responses (9.4%) and 13 partial responses (40.6%) reported. Furthermore, the disease remained stable in 7 patients (21.9%) and progressed in only 9 patients (28.1%). CONCLUSIONS: The results show that high response rates can be achieved with the combination of paclitaxel and cisplatin, even in heavily pretreated breast carcinoma patients. The combination of paclitaxel plus cisplatin was found to be highly efficacious and well tolerated.

Matrix metalloproteinase-2 immunoreactive protein: a marker of aggressiveness in breast carcinoma.

BACKGROUND: Previous studies have shown that matrix metalloproteinase-2 (MMP-2) (a 72-kilodalton Type IV collagenase/gelatinase A) is associated with breast carcinoma, but to the authors' knowledge there are no reports showing that it is prognostic for overall survival. METHODS: Expression of the immunoreactive protein for MMP-2 was evaluated in tissue sections from primary breast carcinomas of 177 patients with a monoclonal antibody to MMP-2 using an immunohistochemical technique. RESULTS: Approximately 84% of the samples were MMP-2 positive, with 22% being strongly positive. Positive MMP-2 immunostaining was prognostic for shortened survival. After 10 years 56% of the patients with tumors that were strongly positive for MMP-2 were alive, whereas 88% of patients with an MMP-2 negative tumor and 70% of patients with weakly or moderately positive tumors were still alive (chi-square test = 7.4; P < 0.01, log rank analysis). MMP-2 positivity was linked with an unfavorable prognosis regardless of the age of the patient, tumor grade, receptor status of the tumor, and stage of disease. These results were confirmed by a multivariate analysis in which MMP-2 positivity emerged as an independent prognostic factor for poor survival. CONCLUSIONS: To the authors' knowledge this study is the first time that MMP-2 immunoreactive protein has been associated strongly with a shortened survival independent of major prognostic indicators in patients with primary breast carcinoma, increasing the risk of death 3.6-fold during the first 10 years of follow-up.