erbB-2 and response to doxorubicin in patients with axillary lymph node-positive, hormone receptor-negative breast cancer
erbB-2 and response to doxorubicin in patients with axillary lymph node-positive, hormone receptor-negative breast cancer
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DOI：
10.1093/jnci/90.18.1361
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发表时间：
1998-09-16
影响因子：
10.3
通讯作者：
Wolmark, N
中科院分区：
文献类型：
--
作者：
Paik, SM;Bryant, J;Wolmark, N
背景：乳腺癌细胞中erbB-2蛋白的过度表达被认为是阿霉素疗效的预测指标。为了检验这一假设，设计了一项回溯性研究。方法：在国家外科辅助乳肠计划B-11方案中，腋窝淋巴结阳性、激素受体阴性的乳腺癌患者随机分为L-苯丙氨酸芥末+5-氟尿嘧啶(PF)或L-苯丙氨酸芥末+5-氟尿嘧啶(5-FU)+阿霉素组(638例)，采用免疫组织化学方法检测肿瘤细胞中erbB-2的表达。在无病生存期(DFS)、无复发生存期(RFS)、无复发生存期(RFS)和远处无病生存期(DDFS)方面，统计分析以检验治疗与erbB-2状态(阳性与阴性)之间的交互作用，报告的P值是双向的。结果：在所研究的638例肿瘤中，有239例(37.5%)有erbB-2过表达(即免疫组织化学染色阳性)。过度表达与肿瘤大小(P=0.02)、雌激素受体缺乏(P=0.008)和阳性淋巴结数(P=0.0001)有关。经过13.5年的平均研究，对于erbB-2阳性肿瘤DFS患者，阿霉素的临床益处(PAF和PF)具有统计学意义：相对失败风险(RR)=0.60(95%可信区间[CI]=0.44-0.83)，P=.001；生存率：RR=0.66(95%CI=0.47~0.92)，P=0.01；RFS：RR=0.58(95%CI=0.42~0.82)，P=.002；DDFS：RR=0.61(95%CI=0.44~0.85)，P=.003。生存率：RR=0.90(95%CI=0.69-1.19)，P=0.47；RFS：RR=0.88(95%CI=0.67-1.16)，P=0.37；DFS：RR=1.03(95%CI=0.79-1.35)，P=.84，DFS(P=0.02)和DFS(P=0.02)之间的交互作用对生存期(P=0.15)或RFS(P=0.06)无统计学意义。结论：这些数据支持多柔比星治疗erbB-2阳性乳腺癌患者优先受益的假说。
Background: Overexpression of the erbB-2 protein by breast cancer cells has been suggested to be a predictor of response to doxorubicin. A retrospective study was designed to test this hypothesis. Methods: In National Surgical Adjuvant Breast and Bowel Project protocol B-ll, patients with axillary lymph node-positive, hormone receptor-negative breast cancer were randomly assigned to receive either L-phenylalanine mustard plus 5-fluorouracil (PF) or a combination of L-phenylalanine mustard, 5-fluorouracil, and doxorubicin (PAF), Tumor cell expression of erbB-2 was determined by immunohistochemistry for 638 of 682 eligible patients. Statistical analyses were performed to test for interaction between treatment and erbB-2 status (positive versus negative) with respect to disease-free survival (DFS), survival, recurrence-free survival (RFS), and distant disease-free survival (DDFS), Reported P values are two-sided. Results: Overexpression of erbB-2 (i.e., positive immunohistochemical staining) was observed in 239 (37.5%) of the 638 tumors studied. Overexpression was associated with tumor size (P = .02), lack of estrogen receptors (P = .008), and the number of positive lymph nodes (P = .0001), After a mean time on study of 13.5 years, the clinical benefit from doxorubicin (PAF versus PF) was statistically significant for patients with erbB-2-positive tumors-DFS: relative risk of failure (RR) = 0.60 (95% confidence interval [CI] = 0.44-0.83), P = .001; survival: RR = 0.66 (95% CI = 0.47-0.92), P = .01; RFS: RR = 0.58 (95% CI = 0.42-0.82), P = .002; DDFS: RR = 0.61 (95% CI = 0.44-0.85), P = .003, However, it was not significant for patients with erbB-2-negative tumors-DFS: RR = 0.96 (95% CI = 0.75-1.23), P = .74; survival: RR = 0.90 (95% CI = 0.69-1.19), P = .47; RFS: RR = 0.88 (95% CI = 0.67-1.16), P = .37; DDFS: RR = 1.03 (95% CI = 0.79-1.35), P = .84, Interaction between doxorubicin treatment and erbB-2 overexpression was statistically significant for DFS (P = .02) and DDFS (P = .02) but not for survival (P = .15) or RFS (P = .06), Conclusions: These data support the hypothesis of a preferential benefit from doxorubicin in patients with erbB-2-positive breast cancer.