Thomssen C, Oppelt P, Jänicke F, Ulm K, Harbeck N, Höfler H, Kuhn W, Graeff H, Schmitt M
Universitätsfrauenklinik Eppendorf, Hamburg, Germany.
Anticancer Res. 1998 May-Jun;18(3C):2173-80.
In node-negative breast cancer, 70% of patients are cured by surgery alone and thus should be spared the necessity of systemic adjuvant treatment. Histomorphological and tumor biological prognostic factors may be employed to assess the patient's risk profile with regard to disease recurrence and death. To evaluate the relationship between tumor biological factors and the metastatic potential of primary breast cancer, proteolytic factors uPA, PAI-1, and cathepsin L, which are associated with tumor invasion and metastasis, were determined in breast cancer tissue extracts by ELISA and the values assessed by uni- and multivariate analysis as well as CART (classification and regression trees) in comparison with traditional prognostic factors. Cysteine protease cathepsin L, serine protease uPA, and the protease inhibitor PAI-1 were determined by ELISA in extracts of primary tumors of 103 node-negative breast cancer patients and values assessed by univariate and multivariate analysis in comparison with traditional prognostic factors (tumor size, steroid hormone receptor status, grading, vessel invasion, menopausal status). Median follow-up of patients still alive at time of follow-up was 56.5 months (range 34-88). PAI-1, cathepsin L, tumor size, grading, and steroid hormone receptor status but not uPA, vessel invasion, and menopausal status were of prognostic relevance for disease-free survival (univariate analysis). Multivariate analysis of disease-free survival (Cox proportional hazards model) disclosed PAI-1 (relative risk of 8.6, p = 0.0001) to be the only strong and statistically independent prognostic factor. By CART-analysis, however, the combination of PAI-1 (< or = 14 ng/mg protein) and cathepsin L (< or = 1,100 ng/mg protein) allowed the identification of a subgroup comprising 68% of the node-negative breast cancer patients having a very low risk of disease recurrence (2/70; incidence of 0.8% per year) versus the high-risk group with PAI-1 (> 14 ng/mg protein) and cathepsin L (> 1,100 ng/mg protein) showing an increased recurrence rate (14/33; incidence of 8.6% per year). We conclude that by the combined determination of PAI-1 and cathepsin L tumor levels low-risk node-negative breast cancer patients may be identified. These patients most probably will not benefit from systemic adjuvant therapy.
在淋巴结阴性的乳腺癌患者中，70%的患者仅通过手术即可治愈，因此无需进行全身辅助治疗。组织形态学和肿瘤生物学预后因素可用于评估患者疾病复发和死亡的风险状况。为了评估肿瘤生物学因素与原发性乳腺癌转移潜能之间的关系，通过酶联免疫吸附测定法（ELISA）在乳腺癌组织提取物中测定了与肿瘤侵袭和转移相关的蛋白水解因子尿激酶型纤溶酶原激活物（uPA）、纤溶酶原激活物抑制剂-1（PAI-1）和组织蛋白酶L，并通过单因素和多因素分析以及分类与回归树（CART）评估这些值，同时与传统预后因素进行比较。通过ELISA在103例淋巴结阴性乳腺癌患者的原发性肿瘤提取物中测定了半胱氨酸蛋白酶组织蛋白酶L、丝氨酸蛋白酶uPA和蛋白酶抑制剂PAI-1，并通过单因素和多因素分析评估这些值，同时与传统预后因素（肿瘤大小、类固醇激素受体状态、分级、血管侵犯、绝经状态）进行比较。随访时仍存活患者的中位随访时间为56.5个月（范围34 - 88个月）。PAI-1、组织蛋白酶L、肿瘤大小、分级和类固醇激素受体状态而非uPA、血管侵犯和绝经状态与无病生存期具有预后相关性（单因素分析）。无病生存期的多因素分析（Cox比例风险模型）显示PAI-1（相对风险为8.6，p = 0.0001）是唯一强有力且具有统计学独立性的预后因素。然而，通过CART分析，PAI-1（≤14 ng/mg蛋白）和组织蛋白酶L（≤1100 ng/mg蛋白）的组合能够识别出一个亚组，该亚组包含68%的淋巴结阴性乳腺癌患者，其疾病复发风险极低（2/70；每年发病率为0.8%），而PAI-1（>14 ng/mg蛋白）和组织蛋白酶L（>1100 ng/mg蛋白）的高危组复发率增加（14/33；每年发病率为8.6%）。我们得出结论，通过联合测定PAI-1和组织蛋白酶L的肿瘤水平，可以识别出低风险的淋巴结阴性乳腺癌患者。这些患者很可能无法从全身辅助治疗中获益。
