Leppä Sirpa, Saarto Tiina, Vehmanen Leena, Blomqvist Carl, Elomaa Inkeri
Department of Oncology, Helsinki University Central Hospital, PO Box 180, FIN-00029 Helsinki, Finland.
Clin Cancer Res. 2004 Feb 1;10(3):1057-63. doi: 10.1158/1078-0432.ccr-03-0047.
The aim of this study was to determine whether serum matrix metalloproteinase (MMP) -2 and MMP-9 levels could predict overall and disease-free survival in primary node-positive breast cancer.
MMP-2 and MMP-9 levels were quantitatively measured in serum after surgery from 133 patients with primary node-positive breast cancer using enzyme-linked immunoassays. All of the patients received adjuvant therapy, postmenopausal endocrine treatment (tamoxifen or toremifen for 3 years) and premenopausal six cycles of CMF chemotherapy. The follow-up time for all of the patients was 5 years.
Overall survival (OS) and disease-free survival (DFS) rates were better among patients with low MMP-2 levels than in patients with high levels (OS, 91% versus 75%, P = 0.020; DFS, 82% versus 58%, P = 0.005). The appearance of bone and visceral metastases was also significantly lower in patients with low serum MMP-2 levels (bone metastases, 10% versus 23%, P = 0.050; visceral metastases, 12% versus 34%, P = 0.018). The prognostic value of MMP-2 levels was most pronounced among a subgroup of estrogen receptor-positive patients (OS, 96% versus 78%, P = 0.052; DFS, 85% versus 58%, P = 0.014), whereas no significant difference was found among estrogen receptor-negative patients (OS, 73% versus 69%, P = 0.25; DFS, 73% versus 63%, P = 0.32). In multivariate analysis, MMP-2 level together with nodal status (NS), progesterone receptor (PgR), and tumor size (T) remained independent predictors for DFS (NS, P = 0.002; PgR, P = 0.004; T, P = 0.023; MMP2, P = 0.039) and OS (NS, P = 0.0002; PgR, P = 0.004; T, P = 0.004; MMP2, P = 0.032). MMP-9 levels did not correlate with survival.
The results suggest that serum postoperative MMP-2 level is a predictor of DFS and OS, and could help to stratify breast cancer patients with primary node-positive disease into low- and high-risk groups.
本研究旨在确定血清基质金属蛋白酶（MMP）-2和MMP-9水平是否可预测原发性淋巴结阳性乳腺癌的总生存期和无病生存期。
采用酶联免疫分析法对133例原发性淋巴结阳性乳腺癌患者术后血清中的MMP-2和MMP-9水平进行定量检测。所有患者均接受辅助治疗，绝经后内分泌治疗（他莫昔芬或托瑞米芬治疗3年）以及绝经前6周期的CMF化疗。所有患者的随访时间为5年。
MMP-2水平低的患者的总生存期（OS）和无病生存期（DFS）率高于MMP-2水平高的患者（OS，91%对75%，P = 0.020；DFS，82%对58%，P = 0.005）。血清MMP-2水平低的患者发生骨转移和内脏转移的情况也显著更低（骨转移，10%对23%，P = 0.050；内脏转移，12%对34%，P = 0.018）。MMP-2水平的预后价值在雌激素受体阳性患者亚组中最为显著（OS，96%对78%，P = 0.052；DFS，85%对58%，P = 0.014），而在雌激素受体阴性患者中未发现显著差异（OS，73%对69%，P = 0.25；DFS，73%对63%，P = 0.32）。在多变量分析中，MMP-2水平与淋巴结状态（NS）、孕激素受体（PgR）和肿瘤大小（T）一起仍是DFS（NS，P = 0.002；PgR，P = 0.004；T，P = 0.023；MMP2，P = 0.039）和OS（NS，P = 0.0002；PgR，P = 0.00
