Prognostic and predictive effects of immunohistochemical factors in high-risk primary breast cancer patients
Prognostic and predictive effects of immunohistochemical factors in high-risk primary breast cancer patients
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DOI：
10.1158/1078-0432.ccr-05-1340
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发表时间：
2006-01-01
影响因子：
11.5
通讯作者：
Löning, T
中科院分区：
文献类型：
--
作者：
Kröger, N;Milde-Langosch, K;Löning, T
目的：在一项高危乳腺癌大剂量化疗与标准剂量化疗的随机对照研究中，分析免疫组织化学因素对乳腺癌预后和预后的影响。实验设计：分析302例高危乳腺癌组织标本中Ki-67、p16、maspin、bcl2、hER2/neu和p53的表达。结果：在调整治疗、肿瘤大小和雌激素受体后的单因素分析中，her2/neu阳性(P=0.001)为阴性，bcl2阳性(P=0.003)是无事件生存的阳性预后因素。在多因素分析中，HER2/neu阳性(危险比3.68；95%可信区间2.01~6.73；P=0.0001)对无事件生存率有负面影响，而p53阳性(危险比0.57；95%可信区间0.34~0.95；P=0.03)和bcl2阳性(危险比0.35；95%可信区间0.19~0.64；P=0.0006)与较好的无事件生存有关。分析免疫组织化学因素的预测作用，显示P53与治疗之间存在交互作用(P=0.005)。大剂量化疗与标准化疗的风险比在p53阴性患者中估计为2.3(95%可信区间，0.67~7.92)，在p53阳性患者中估计为0.46(95%可信区间，0.2~1.07)，这表明大剂量化疗在p53阳性患者中具有优越性，而在p53阴性患者中处于劣势。结论：HER2/neu和Bcl2是高危乳腺癌患者的预后因素，但不是预测因素；P53阳性患者从大剂量化疗中受益可能比标准化疗多，P53阴性患者从标准化疗中受益更多。
Purpose: To analyze prognostic and predictive effects of immunohistochemical factors within a randomized study of high-dose versus standard-dose chemotherapy in high-risk breast cancer with > 10 involved lymph nodes.Experimental Design: Histopathologic specimens in 188 of 302 patients were analyzed for Ki-67, p16, maspin, Bcl-2, Her2/neu, and p53.Results: In a univariate analysis after adjustment for therapy, tumor size, and estrogen receptor, Her2/neu positivity (P = 0.001) was a negative and Bcl2 positivity (P = 0.003) was a positive prognostic factor for event-free survival. In a multivariate analysis, Her2/neu positivity (hazard ratio, 3.68; 95% confidence interval, 2.01-6.73; P = 0.0001) had a negative influence on event-free survival, whereas p53 positivity (hazard ratio, 0.57; 95% confidence interval, 0.34-0.95; P = 0.03) and Bcl2 positivity (hazard ratio, 0.35; 95% confidence interval, 0.19-0.64; P = 0.0006) were associated with a better event-free survival. Analyzing the predictive effect of the immunohistochemical factors, an interaction between p53 and treatment could be shown (P = 0.005). The hazard ratio for high-dose chemotherapy versus standard chemotherapy is estimated as 2.3 (95% confidence interval, 0.67-7.92) in p53-negative patients and as 0.46 (95% confidence interval, 0.2-1.07) in p53-positive patients, which indicates a superiority of high-dose chemotherapy in p53-positive patients and an inferiority in p53-negative patients. No interactive effect could be shown for the other factors.Conclusions: Her2/neu and Bcl-2 are prognostic but not predictive factors in patients with high-risk primary breast cancer; p53-positive patients might benefit more from high-dose chemotherapy than from standard chemotherapy, and p53-negative patients might benefit more from standard chemotherapy than from high-dose therapy.