Ki67 Expression and Docetaxel Efficacy in Patients With Estrogen Receptor-Positive Breast Cancer
Ki67 Expression and Docetaxel Efficacy in Patients With Estrogen Receptor-Positive Breast Cancer
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DOI：
10.1200/jco.2008.18.2808
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发表时间：
2009-06-10
影响因子：
45.3
通讯作者：
Roche, Henri
中科院分区：
文献类型：
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作者：
Penault-Llorca, Frederique;Andre, Fabrice;Roche, Henri
目的雌激素受体（ER）阳性乳腺癌患者的辅助化疗适应症存在争议。我们分析了Ki67、HER2和孕激素受体（PR）表达对多西紫杉醇治疗er阳性、淋巴结阳性乳腺癌患者疗效的预测价值。采用免疫组化方法检测了798例er阳性乳腺癌患者的肿瘤样本中Ki67、HER2和PR的表达。PACS01是一项评估多西紫杉醇疗效的随机试验。使用Cox模型对年龄、肿瘤大小、淋巴结累及、治疗组和生物标志物进行调整，评估风险降低程度。通过相互作用试验评估生物标志物的预测价值。无病生存期（DFS）是主要终点。结果ski67、HER2和PR的表达率分别为21%、9%和62%。er阳性/ ki67阳性肿瘤与多西他赛相关的复发风险比为0.51 (95% CI， 0.26至1.01)，er阳性/ ki67阴性肿瘤与多西他赛相关的复发风险比为1.03 (95% CI， 0.69至1.55)（相互作用比：0.53;95% CI， 0.24至1.16;P = 0.11）。多西紫杉醇治疗ER阳性/ ki67阴性和ER阳性/ ki67阳性肿瘤患者的5年DFS分别为81% （95% CI, 76% - 86%）和84% (95% CI, 75% - 93%)，而氟尿嘧啶、表柔比星和顺铂治疗ER阳性/ ki67阴性和ER阳性/ ki67阳性肿瘤患者的5年DFS分别为81% （95% CI, 76% - 86%）和62% （95% CI, 52% - 72%）。多西他赛和HER2之间没有相互作用的趋势（相互作用比：0.83;95% CI, 0.35 ~ 1.94; P = 0.66），多西他赛和PR之间也没有相互作用的趋势（相互作用比：0.89;95% CI, 0.47 ~ 1.66; P = 0.71）。结论ki67表达确定了ER阳性乳腺癌患者的一个亚群，这些患者可能对多西紫杉醇辅助治疗敏感。
PurposeThe indications of adjuvant chemotherapy for patients with estrogen receptor (ER)-positive breast cancer are controversial. We analyzed the predictive value of Ki67, HER2, and progesterone receptor (PR) expression for the efficacy of docetaxel in patients with ER-positive, node-positive breast cancer.Patients and MethodsExpression of Ki67, HER2, and PR was measured by immunohistochemistry in tumor samples from 798 patients with ER-positive breast cancer who participated in PACS01, a randomized trial that evaluated the efficacy of docetaxel. Risk reduction was evaluated using a Cox model adjusted for age, tumor size, nodal involvement, treatment arm, and biomarkers. The predictive value of biomarkers was assessed by an interaction test. Disease-free survival (DFS) was the primary end point.ResultsKi67, HER2, and PR were expressed in 21%, 9%, and 62% of samples, respectively. Hazard ratios for relapse associated with docetaxel were 0.51 (95% CI, 0.26 to 1.01) in ER-positive/Ki67-positive tumors and 1.03 (95% CI, 0.69 to 1.55) in ER-positive/Ki67-negative tumors (ratio for interaction: 0.53; 95% CI, 0.24 to 1.16; P = .11). Five-year DFS rates were 81% (95% CI, 76% to 86%) and 84% (95% CI, 75% to 93%) in patients with ER-positive/Ki67-negative and ER- positive/Ki67positive tumors treated with docetaxel and 81% (95% CI, 76% to 86%) and 62% (95% CI, 52% to 72%) in patients with ER-positive/Ki67-negative and ER-positive/Ki67-positive tumors treated with fluorouracil, epirubicin, and cisplatin. No trend for interaction was observed between docetaxel and HER2 (ratio for interaction: 0.83; 95% CI, 0.35 to 1.94; P = .66), nor between docetaxel and PR (ratio for interaction: 0.89; 95% CI, 0.47 to 1.66; P = .71).ConclusionKi67 expression identifies a subset of patients with ER- positive breast cancer who could be sensitive to docetaxel treatment in the adjuvant setting.