Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer
Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer
复制标题
DOI：
10.1001/jama.295.14.1658
复制
发表时间：
2006-04-12
影响因子：
120.7
通讯作者：
Winer, EP
中科院分区：
文献类型：
--
作者：
Berry, DA;Cirrincione, C;Winer, EP
乳腺癌雌激素受体（ER）状态有助于预测内分泌治疗的获益。它也可能有助于预测哪些患者受益于辅助chemotherapy.Objective比较ER阴性vs ER阳性肿瘤患者辅助化疗的获益差异。设计、设置和患者来自癌症和白血病组B和美国乳腺癌组间的试验数据进行分析;使用随时间推移的风险和多变量模型比较ER状态对患者结局的影响。比较（1）：环磷酰胺、阿霉素和氟尿嘧啶3种方案的随机试验（1985年1月至1991年4月）;（2）3剂多柔比星联合环磷酰胺，随后联合或不联合紫杉醇（1994年5月至1997年4月）;（3）序贯多柔比星、紫杉醇和环磷酰胺，同时多柔比星和环磷酰胺，然后紫杉醇，以及3周与2周周期（1997年9月至1999年3月）。共6644淋巴结阳性乳腺癌患者接受了辅助治疗。主要结果指标无病生存率和总生存率。结果对于ER阴性肿瘤，化疗改善降低了复发的相对风险分别为21%，25%和23%，在3项研究中，和55%，比较第一项研究中的最低剂量与第三项研究中的双周周期。在3项研究中，他莫昔芬治疗ER阳性肿瘤的相应相对风险降低分别为9%、12%和8%，总体为26%。在ER阴性和ER阳性患者中，与化疗改善相关的总体死亡率降低分别为55%和23%。所有个体ER阴性比较和无ER阳性比较均具有统计学显著性。与ER阳性患者相比，ER阴性患者化疗的绝对获益更大：接受化疗的ER阴性患者5年无病生存率高22.8%，而ER阳性患者为7.0%;总生存率分别为16.7%和4.0%。结论在淋巴结阳性乳腺癌、ER阴性乳腺癌、与第一项研究中使用的低剂量环磷酰胺、多柔比星和氟尿嘧啶相比，每两周一次的多柔比星/环磷酰胺加紫杉醇使复发率和死亡率降低了50%以上。
Context Breast cancer estrogen-receptor (ER) status is useful in predicting benefit from endocrine therapy. It may also help predict which patients benefit from advances in adjuvant chemotherapy.Objective To compare differences in benefits from adjuvant chemotherapy achieved by patients with ER-negative vs ER-positive tumors.Design, Setting, and Patients Trial data from the Cancer and Leukemia Group B and US Breast Cancer Intergroup analyzed; patient outcomes by ER status compared using hazards over time and multivariate models. Randomized trials comparing (1): 3 regimens of cyclophosphamide, doxorubicin, and fluorouracil (January 1985 to April 1991); (2) 3 doses of doxorubicin concurrent with cyclophosphamide, with or without subsequent paclitaxel (May 1994 to April 1997); (3) sequential doxorubicin, paclitaxel, and cyclophosphamide with concurrent doxorubicin and cyclophosphamide followed by paclitaxel, and also 3-week vs 2-week cycles (September 1997 to March 1999). A total of 6644 node-positive breast cancer patients received adjuvant treatment.Main Outcome Measures Disease-free and overall survival.Results For ER-negative tumors, chemotherapy improvements reduced the relative risk of recurrence by 21%, 25%, and 23% in the 3 studies, respectively, and 55% comparing the lowest dose in the first study with biweekly cycles in the third study. Corresponding relative risk reductions for ER-positive tumors treated with tamoxifen were 9%, 12%, and 8% in the 3 studies, and 26% overall. The overall mortality rate reductions associated with chemotherapy improvements were 55% and 23% among ER-negative and ER-positive patients, respectively. All individual ER-negative comparisons and no ER-positive comparisons were statistically significant. Absolute benefits due to chemotherapy were greater for patients with ER-negative compared with ER-positive tumors: 22.8% more ER-negative patients survived to 5 years disease-free if receiving chemotherapy vs 7.0% for ER-positive patients; corresponding improvements for overall survival were 16.7% vs 4.0%.Conclusion Among patients with node-positive tumors, ER-negative breast cancer, biweekly doxorubicin/cyclophosphamide plus paclitaxel lowers the rate of recurrence and death by more than 50% in comparison with low-dose cyclophosphamide, doxorubicin, and fluorouracil as used in the first study.