Serum TIMP-1 and response to the aromatase inhibitor letrozole versus tamoxifen in metastatic breast cancer
Serum TIMP-1 and response to the aromatase inhibitor letrozole versus tamoxifen in metastatic breast cancer
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DOI：
10.1200/jco.2007.15.4336
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发表时间：
2008-06-01
影响因子：
45.3
通讯作者：
Carney, Walter
中科院分区：
文献类型：
--
作者：
Lipton, Allan;Leitzel, Kim;Carney, Walter
PurposeTo determine the effect of elevated serum TIMP-1 on response of patients with metastatic breast cancer to a aromatase inhibitor versus tamoxifen.Patients and MethodsFive 22 patients estrogen receptor - positive metastatic breast cancer were randomly assigned to receive first-line hormone therapy with letrozole or tamoxifen.血清金属蛋白酶组织抑制剂-1（TIMP-1）水平测定使用酶联免疫吸附试验。ResultsPretreatment血清TIMP-1升高120（23%）的522例。血清TIMP-1升高的患者客观缓解率显著降低（19.2% vs 30.6%;比值比，0.54; P =.01），缓解持续时间（中位数，15.5 vs 26.2个月; P =.001），至治疗进展时间（TTP;中位数，4.5 vs 9.2个月; HR，1.78; P =.0001），至治疗失败的时间（中位数，3.5对9.0个月; HR，1.77; P = 0.0001）和总生存期（中位数，20.3对35.8个月; HR，1.77; P = 0.0001）与治疗前TIMP-1水平正常的患者相比。在血清TIMP-1正常的两组中，来曲唑均优于他莫昔芬（上级（中位TTP，11.8 vs 8.6个月; P =.003）和血清TIMP-1升高组（中位数，6.1 vs 3.2个月; P = 0.03）在多变量分析中，血清TIMP-1升高仍然是TTP缩短的独立预测因素，（HR，1.46; P =.002）和存活率（HR，1.44; P =.002），血清HER-2也是如此。联合分析血清TIMP-1和HER-2/neu赋予额外的能力来预测显着不同的临床outcomes相比，使用任一生物标志物单独。结论患者治疗前血清TIMP-1升高有显着降低的反应和生存。血清TIMP-1是独立的预测和预后因素。阻断TIMP-1和HER-2/neu活性可能对乳腺癌患者亚组有益。
PurposeTo determine the effect of elevated serum TIMP-1 on the response of patients with metastatic breast cancer to an aromatase inhibitor versus tamoxifen.Patients and MethodsFive hundred twenty-two patients estrogen receptor - positive metastatic breast cancer were randomly assigned to receive first-line hormone therapy with letrozole or tamoxifen. Serum tissue inhibitor of metalloproteinases-1 ( TIMP-1) levels were measured using an enzyme-linked immunosorbent assay.ResultsPretreatment serum TIMP-1 was elevated in 120 (23%) of 522 patients. Patients with elevated serum TIMP-1 had a significantly reduced objective response rate (19.2% v 30.6%; odds ratio, 0.54; P =.01), duration of response ( median, 15.5 v 26.2 months; P =.001), time to treatment progression (TTP; median, 4.5 v 9.2 months; HR, 1.78; P =.0001), time to treatment failure ( median, 3.5 v 9.0 months; HR, 1.77; P =.0001), and overall survival ( median, 20.3 v 35.8 months; HR, 1.77; P =.0001) compared with patients with normal pretreatment TIMP-1 levels. Letrozole was superior to tamoxifen in both the normal serum TIMP-1 group ( median TTP, 11.8 v 8.6 months; P =.003) and in the elevated serum TIMP-1 group ( median, 6.1 v 3.2 months; P =.03) In multivariate analysis, elevated serum TIMP-1 remained an independent predictor of both shorter TTP ( HR, 1.46; P =.002) and survival ( HR, 1.44; P =.002), as did serum HER-2. Combined analysis of both serum TIMP-1 and HER-2/neu conferred additional ability to predict significantly different clinical outcomes compared to using either biomarker alone.Conclusion Patients with elevated pretreatment serum TIMP-1 had a significantly reduced response and survival. Serum TIMP-1 was an independent predictive and prognostic factor. Blockade of TIMP-1 and HER-2/neu activity may be beneficial in a subset of patients with breast cancer.