Breast Center, University of Cologne, Kerpener Strasse 34, 50931 Cologne, Germany.
J Clin Oncol. 2009 Dec 20;27(36):6144-51. doi: 10.1200/JCO.2008.19.6261. Epub 2009 Nov 9.
To investigate the potential of Y-box-binding protein YB-1, a multifunctional protein linked to tumor aggressiveness and multidrug resistance, to identify patients with breast cancer likely to benefit from dose-intensified chemotherapy regimens.
YB-1 was immunohistochemically determined in 211 primary tumors from the prospective, randomized West German Study Group WSG-AM-01 trial in high-risk (> or = 10 involved lymph-nodes) breast cancer (HRBC). Predictive impact of YB-1 was assessed by multivariate survival analysis, including time-varying factor-therapy interactions.
At median follow-up of 61.7 months, patients receiving rapidly cycled tandem high-dose therapy (HD; two cycles [2x] epirubicin 90 mg/m(2) and cyclophosphamide 600 mg/m(2) every 14 days, followed by 2x epirubicin 90 mg/m(2), cyclophosphamide 3,000 mg/m(2), and thiotepa 400 mg/m(2) every 21 days) had better disease-free survival (DFS; hazard ratio [HR] = 0.62; 95% CI, 0.44 to 0.89) and overall survival (OS; HR = 0.59; 95% CI, 0.4 to 0.89) than those receiving conventional dose-dense chemotherapy (DD; 4x epirubicin 90 mg/m(2) and cyclophosphamide 600 mg/m(2), followed by 3x cyclophosphamide 600 mg/m(2), methotrexate 40 mg/m(2), and fluorouracil 600 mg/m(2) every 14 days). High YB-1 was associated with aggressive tumor phenotype (negative steroid hormone receptor status, positive human epidermal growth factor receptor 2 and p53 status, high MIB-1, unfavorable tumor grade) and poor OS (median 78 v 97 months; P = .01). In patients with high YB-1, HD yielded a 63-month median DFS (P = .001) and a 46-month median OS advantage (P = .002) versus DD. In multivariate models, patients with high B-1 receiving HD (v DD) had one third the hazard rate after 20 months for DFS and one sixth after 40 months for OS.
In a randomized prospective cancer therapy trial, for the first time, a strong predictive impact of YB-1 on survival has been demonstrated: enhanced benefit from HD (v DD) therapy occurs in HRBC with high YB-1. Future trials could therefore address optimal chemotherapeutic strategies,taking YB-1 into account.
研究多功能蛋白 Y 盒结合蛋白 1（YB-1）在肿瘤侵袭性和多药耐药中的潜在作用，以鉴定可能从强化化疗方案中获益的乳腺癌患者。
对 211 例高危（≥10 个受累淋巴结）乳腺癌（HRBC）患者前瞻性随机德国研究组 WSG-AM-01 试验中的原发性肿瘤进行 YB-1 免疫组织化学检测。通过包括时变因素治疗相互作用的多变量生存分析评估 YB-1 的预测影响。
在中位随访 61.7 个月时，接受快速循环串联高剂量治疗（HD；每 14 天接受 2 次表柔比星 90mg/m2 和环磷酰胺 600mg/m2，随后接受 2 次表柔比星 90mg/m2、环磷酰胺 3000mg/m2 和噻替哌 400mg/m2）的患者无病生存（DFS；危险比[HR] = 0.62；95%CI，0.44 至 0.89）和总生存（OS；HR = 0.59；95%CI，0.4 至 0.89）均优于接受常规剂量密集化疗（DD；4 次表柔比星 90mg/m2 和环磷酰胺 600mg/m2，随后接受 3 次环磷酰胺 600mg/m2、甲氨蝶呤 40mg/m2 和氟尿嘧啶 600mg/m2，每 14 天）。高 YB-1 与侵袭性肿瘤表型（阴性甾体激素受体状态、阳性人表皮生长因子受体 2 和 p53 状态、高 MIB-1、不良肿瘤分级）和较差的 OS 相关（中位 78 与 97 个月；P =.01）。在高 YB-1 患者中，HD 组的中位 DFS 为 63 个月（P =.001），中位 OS 优势为 46 个月（P =.002）。在多变量模型中，接受 HD（与 DD）治疗的高 YB-1 患者在 20 个月时 DFS 的危险率降低了三分之一，在 40 个月时 OS 的危险率降低了六分之一。
在一项随机前瞻性癌症治疗试验中，首次证明 YB-1 对生存有很强的预测影响：在高 YB-1 的 HRBC 中，HD（与 DD）治疗的获益更大。因此，未来的试验可以考虑 YB-1，确定最佳化疗策略。
