Triple-negative high-risk breast cancer derives particular benefit from dose intensification of adjuvant chemotherapy:: results of WSG AM-01 trial
Triple-negative high-risk breast cancer derives particular benefit from dose intensification of adjuvant chemotherapy:: results of WSG AM-01 trial
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DOI：
10.1093/annonc/mdm551
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发表时间：
2008-05-01
影响因子：
50.5
通讯作者：
Mohrmann, S.
中科院分区：
文献类型：
--
作者：
Gluz, O.;Nitz, U. A.;Mohrmann, S.
背景资料：本文评估了在一项前瞻性随机WSG AM- 01试验中，在接受不同化疗剂量强化策略的> 9个受累淋巴结的高危乳腺癌（HRBC）患者中，各种分子标志物的蛋白表达对预后和预测的影响。从236个病人身上提取的石蜡包埋的肿瘤，随机分配接受剂量密集常规化疗，E90 C600 4个周期，随后C600 M40 F600 3个周期，每2周一次（DD）或快速循环串联高剂量方案（E90 C600每2周2个周期，随后E90 C3000 Thiotepa（400）每3周2个周期（HD）），可用于回顾性中心病理学审查（116 HD/ 120 DD）。雌激素受体（ER），孕激素受体（PR），MIB- 1，表皮生长因子受体，和Her-2/ neu的表达进行了评价，使用组织微阵列化学。通过比例风险考克斯回归模型将结果与随访数据和治疗效果相关结果：中位随访61.7个月后，HD组236例患者的5年无事件生存率（EFS）和总生存率（OS）明显更好：EFS：62% vs 41% [风险比（HR）= 0.60，95% CI 0.43 - 0.85，P = 0.004]; OS：76% vs 61%（HR = 0.58，95% CI 0.39 - 0.87，P = 0.007）。在多变量分析中，HD、肿瘤大小< 3 cm、PR阳性、MIB- 1染色阴性和1/ 2级与良好结局相关。交互作用分析显示，在预测效果方面，三阴性（ER/ PR/ Her- 2/ neu）和G3肿瘤从HD中获益最多。结论：串联HD可改善HRBC的EFS和OS。这种治疗效果可能部分归因于在具有不良预后标志物特征的三阴性肿瘤和/或G3亚组中的上级疗效。
Background: This paper evaluates the prognostic and predictive impact of protein expression of various molecular markers in high- risk breast cancer ( HRBC) patients with > 9 involved lymph nodes, who received different chemotherapy dose- intensification strategies within a prospective randomized WSG AM- 01 trial.Materials and methods: Paraffin- embedded tumors from 236 patients, who were randomly assigned to dose-dense conventional chemotherapy with four cycles of E90C600 followed by three cycles of C600M40F600 every 2 weeks ( DD) or a rapidly cycled tandem high- dose regimen with two cycles of E90C600 every 2 weeks followed by two cycles of E90C3000 Thiotepa(400) every 3 weeks ( HD), were available for retrospective central pathological review ( 116 HD/ 120 DD). Expression of estrogen receptor ( ER), progesterone receptor ( PR), MIB- 1, epidermal growth factor receptor, and Her-2/ neu was evaluated immunohistochemically using tissue microarrays. Results were correlated with follow- up data and treatment effects by proportional hazard Cox regression models ( including interaction analysis).Results: After a median follow- up of 61.7 months, 5- year event- free survival ( EFS) as well as overall survival ( OS) rates for the 236 patients were significantly better in the HD arm: EFS: 62% versus 41% [ hazard ratio ( HR) = 0.60, 95% CI 0.43 - 0.85, P = 0.004]; OS: 76% versus 61% ( HR = 0.58, 95% CI 0.39 - 0.87, P = 0.007). In multivariate analysis, HD, tumor size < 3 cm, positive PR, negative MIB- 1 staining, and grade 1/ 2 were associated with favorable outcome. Interaction analysis showed that regarding predictive effects, triple negative ( ER/ PR/ Her- 2/ neu) and G3 tumors derived most benefit from HD.Conclusion: Tandem HD improves both EFS and OS in HRBC. This therapy effect may be partly attributable to superior efficacy in the subgroup of triple- negative tumors and/ or G3 with their poor prognostic marker profile.