Billgren A M, Rutqvist L E, Johansson H, Hägerström T, Skoog L
Department of Oncology and Pathology, Oncologic Center, Radiumhemmet, Karolinska Hospital, S 171 76, Stockholm, Sweden.
Eur J Cancer. 2000 Jul;36(11):1374-80. doi: 10.1016/s0959-8049(00)00114-3.
In the last few years there has been an increased interest in treatment predictive factors in breast cancer patients. The aim of the study was to analyse the role of cathepsin D and plasminogen activator inhibitor-1 (PAI-1) expression as independent prognosticators and to assess their predictive value with respect to tamoxifen treatment. This study comprises 1851 patients with primary breast cancer diagnosed during 1988-1992. Their median age was 62 years (range: 24-91). The end-point was distant disease recurrence-free interval. Adjuvant treatment with tamoxifen was given to 1136 patients (61%). The median follow-up time was 59 months (range: 39-88). Cathepsin D content was shown to be a significant independent prognosticator in multivariate Cox analysis (P=0.02). The optimal cut-off level was 10 fmol/mg protein, other cut-off levels did not improve the results. The level of cathepsin D also appeared to predict the benefit of tamoxifen among oestrogen receptor (ER)-positive patients although this result did not reach statistical significance (P=0.09). In a multivariate Cox analysis including 497 patients PAI-1 content was shown to be a significant independent prognosticator (P=0.003) but did not appear to predict the benefit of tamoxifen treatment. The optimal cut-off level appeared to be 3 ng/mg protein, which was close to the median value 2.5 ng/mg (range: 0-51). We conclude that cathepsin D is a significant independent prognosticator and may possibly also predict the benefit of tamoxifen amongst ER-positive patients. PAI-1 was also found to be a strong independent prognosticator but no treatment interaction with adjuvant tamoxifen was found.
在过去几年中，人们对乳腺癌患者的治疗预测因素越来越感兴趣。本研究的目的是分析组织蛋白酶D和纤溶酶原激活物抑制剂-1（PAI-1）表达作为独立预后指标的作用，并评估它们对他莫昔芬治疗的预测价值。本研究纳入了1988年至1992年间诊断的1851例原发性乳腺癌患者。他们的中位年龄为62岁（范围：24 - 91岁）。终点是远处疾病无复发生存期。1136例患者（61%）接受了他莫昔芬辅助治疗。中位随访时间为59个月（范围：39 - 88个月）。在多变量Cox分析中，组织蛋白酶D含量被证明是一个显著的独立预后指标（P = 0.02）。最佳截断水平为10 fmol/mg蛋白，其他截断水平并未改善结果。组织蛋白酶D水平似乎也能预测雌激素受体（ER）阳性患者使用他莫昔芬的获益，尽管这一结果未达到统计学显著性（P = 0.09）。在一项纳入497例患者的多变量Cox分析中，PAI-1含量被证明是一个显著的独立预后指标（P = 0.003），但似乎不能预测他莫昔芬治疗的获益。最佳截断水平似乎为3 ng/mg蛋白，接近中位数2.5 ng/mg（范围：0 - 51）。我们得出结论，组织蛋白酶D是一个显著的独立预后指标，并且可能还能预测ER阳性患者使用他莫昔芬的获益。PAI-1也被发现是一个强有力的独立预后指标，但未发现与他莫昔芬辅助治疗有相互作用。
