Brustzentrum, Frauenklinik Maistrasse, Universitaet München, 80337 Munich, Germany.
Eur J Cancer. 2013 May;49(8):1825-35. doi: 10.1016/j.ejca.2013.01.007. Epub 2013 Mar 13.
Final 10-year analysis of the prospective randomised Chemo-N0 trial is presented. Based on the Chemo-N0 interim results and an European Organisation for Research and Treatment of Cancer (EORTC) pooled analysis (n=8377), American Society of Clinical Oncology (ASCO) and Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) guidelines recommend invasion and metastasis markers urokinase-type plasminogen activator (uPA)/plasminogen activator inhibitor-1 (PAI-1) for risk assessment and treatment decision in node-negative (N0) breast cancer (BC).
The final Chemo-N0 trial analysis (recruitment 1993-1998; n=647; 12 centres) comprises 113 (5-167) months of median follow-up. Patients with low-uPA and PAI-1 tumour tissue levels (n=283) were observed. External quality assurance guaranteed uPA/PAI-1 enzyme-linked immunosorbent assay (ELISA) standardisation. Of 364 high uPA and/or PAI-1 patients, 242 agreed to randomisation for CMF chemotherapy (n=117) versus observation (n=125).
Actuarial 10-year recurrence rate (without any adjuvant systemic therapy) for high-uPA/PAI-1 observation group patients (randomised and non-randomised) was 23.0%, in contrast to only 12.9% for low-uPA/PAI-1 patients (plog-rank=0.011). High-risk patients randomised to cyclophosphamide-methotrexate-5-fluorouracil (CMF) therapy had a 26.0% lower estimated probability of disease recurrence than those randomised for observation (intention-to-treat (ITT)-analysis: hazard ratio (HR) 0.74 (0.44-1.27); plog-rank=0.28). Per-protocol analysis demonstrated significant treatment benefit: HR 0.48 (0.26-0.88), p=0.019, disease-free survival (DFS) Cox regression, adjusted for tumour stage and grade.
Chemo-N0 is the first prospective biomarker-based therapy trial in early BC defining patients reaching good long-term DFS without adjuvant systemic therapy. Using a standardised uPA/PAI-1 ELISA, almost half of N0-patients could be spared chemotherapy, while high-risk patients benefit from adjuvant chemotherapy. These 10-year results validate the long-term prognostic impact of uPA/PAI-1 and the benefit from adjuvant chemotherapy in the high-uPA/PAI-1 group at highest level of evidence. They thus support the guideline-based routine use of uPA/PAI-1 for risk-adapted individualised therapy decisions in N0 breast cancer.
呈现前瞻性随机 Chemo-N0 试验的最终 10 年分析。基于 Chemo-N0 的中期结果和欧洲癌症研究与治疗组织（EORTC）的荟萃分析（n=8377），美国临床肿瘤学会（ASCO）和妇科肿瘤学工作组（AGO）指南建议侵袭和转移标志物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）用于评估风险和治疗决策在淋巴结阴性（N0）乳腺癌（BC）中。
最终的 Chemo-N0 试验分析（招募 1993-1998 年；n=647；12 个中心）包括 113（5-167）个月的中位随访。具有低 uPA 和 PAI-1 肿瘤组织水平的患者（n=283）进行观察。外部质量保证保证了 uPA/PAI-1 酶联免疫吸附测定（ELISA）的标准化。在 364 例高 uPA 和/或 PAI-1 患者中，有 242 例同意接受 CMF 化疗（n=117）与观察（n=125）的随机分组。
高 uPA/PAI-1 观察组患者（随机和非随机）未经任何辅助系统治疗的 10 年复发率（无任何辅助系统治疗）为 23.0%，而低 uPA/PAI-1 患者为 12.9%（对数秩检验=0.011）。随机接受环磷酰胺-甲氨蝶呤-5-氟尿嘧啶（CMF）治疗的高危患者比随机接受观察的患者估计疾病复发的可能性低 26.0%（意向治疗（ITT）分析：风险比（HR）0.74（0.44-1.27）；对数秩检验=0.28）。方案分析显示出显著的治疗益处：HR 0.48（0.26-0.88），p=0.019，无病生存（DFS）Cox 回归，调整了肿瘤分期和分级。
Chemo-N0 是第一个在早期 BC 中基于生物标志物的前瞻性治疗试验，定义了无辅助系统治疗可获得良好长期 DFS 的患者。使用标准化的 uPA/PAI-1 ELISA，几乎一半的 N0 患者可以避免化疗，而高危患者则受益于辅助化疗。这些 10 年的结果验证了 uPA/PAI-1 的长期预后影响，以及在证据水平最高的高 uPA/PAI-1 组中辅助化疗的益处。因此，它们支持基于指南的常规使用 uPA/PAI-1 进行风险适应性个体化治疗决策在 N0 乳腺癌中。
