erbB-2与腋窝淋巴结阳性、激素受体阴性乳腺癌患者对多柔比星的反应

erbB-2 and response to doxorubicin in patients with axillary lymph node-positive, hormone receptor-negative breast cancer.

作者信息

Paik S, Bryant J, Park C, Fisher B, Tan-Chiu E, Hyams D, Fisher E R, Lippman M E, Wickerham D L, Wolmark N

机构信息

National Surgical Adjuvant Breast and Bowel Project, Department of Human Oncology, Allegheny University of Health Sciences, Pittsburgh, PA 15212-5234, USA.

出版信息

J Natl Cancer Inst. 1998 Sep 16;90(18):1361-70. doi: 10.1093/jnci/90.18.1361.

DOI:10.1093/jnci/90.18.1361

PMID:9747867

Abstract

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-11, 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.

摘要

背景

乳腺癌细胞中erbB-2蛋白的过表达被认为是对多柔比星反应的一个预测指标。一项回顾性研究旨在验证这一假设。

方法

在国家外科辅助乳腺和肠道项目协议B-11中，腋窝淋巴结阳性、激素受体阴性的乳腺癌患者被随机分配接受左旋苯丙氨酸氮芥加5-氟尿嘧啶（PF）或左旋苯丙氨酸氮芥、5-氟尿嘧啶和多柔比星的联合治疗（PAF）。对682例符合条件患者中的638例进行免疫组织化学检测，以确定肿瘤细胞erbB-2的表达。进行统计学分析，以检验治疗与erbB-2状态（阳性与阴性）在无病生存期（DFS）、总生存期、无复发生存期（RFS）和远处无病生存期（DDFS）方面的相互作用。报告的P值为双侧。

结果

在所研究的638个肿瘤中，239个（37.5%）观察到erbB-2过表达（即免疫组织化学染色阳性）。过表达与肿瘤大小（P = 0.02）、雌激素受体缺乏（P = 0.008）以及阳性淋巴结数量（P = 0.0001）相关。经过平均13.5年的研究期后，对于erbB-2阳性肿瘤患者，多柔比星（PAF对比PF）带来的临床获益具有统计学意义——DFS：失败相对风险（RR）= 0.60（95%置信区间[CI]=0.44 - 0.83），P = 0.001；总生存期：RR = 0.66（95% CI = 0.47 - 0.92），P = 0.01；RFS：RR = 0.58（95% CI = 0.42 - 0.82），P = 0.002；DDFS：RR = 0.61（95% CI = 0.44 - 0.85），P = 0.003。然而，对于erbB-2阴性肿瘤患者则无统计学意义——DFS：RR = 0.96（95% CI = 0.75 - 1.23），P = 0.74；总生存期：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；DDFS：RR = 1.03（95% CI = 0.79 - 1.35），P = 0.84。多柔比星治疗与erbB-2过表达之间的相互作用在DFS（P = 0.02）和DDFS（P = 0.02）方面具有统计学意义，但在总生存期（P = 0.15）或RFS（P = 0.06）方面无统计学意义。